A Study of TAK-981 Given With Pembrolizumab in Participan... | NCT04381650

ID	Type	Description	Link
2020-004325-23	EudraCT Number
jRCT2031210417	Registry Identifier	jRCT

Name	Class
Takeda Development Center Americas, Inc.	INDUSTRY

Label	Type	Description	Intervention Names
Dose Escalation: TAK-981 40 mg + Pembrolizumab	Experimental	Participants received TAK-981 40 mg, intravenous (IV) infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the recommended Phase 2 dose (RP2D) was determined (for a maximum of 24 months).	Drug: TAK-981 Drug: Pembrolizumab
Dose Escalation: TAK-981 60 mg + Pembrolizumab	Experimental	Participants received TAK-981 60 mg, intravenous (IV) infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).	Drug: TAK-981 Drug: Pembrolizumab
Dose Escalation: TAK-981 90 mg + Pembrolizumab	Experimental	Participants received TAK-981 90 mg, intravenous (IV) infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).	Drug: TAK-981 Drug: Pembrolizumab
Dose Escalation: TAK-981 120 mg + Pembrolizumab	Experimental	Participants received TAK-981 120 mg, intravenous (IV) infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).

Name	Type	Description	Arm Group Labels	Other Names
TAK-981	Drug	TAK-981 IV infusion.	Dose Escalation: TAK-981 120 mg + Pembrolizumab Dose Escalation: TAK-981 40 mg + Pembrolizumab Dose Escalation: TAK-981 60 mg + Pembrolizumab

Measure	Description	Time Frame
Phase 1: Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs)	An adverse event (AE) is any untoward medical occurrence in a participant administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. A TEAE is defined as an AE that occurs after administration of first dose of study drug and through 30 days after last dose of study drug or until start of subsequent antineoplastic therapy. AEs were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0 except cytokine release syndrome (CRS), which was graded according to American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading for CRS.	Up to approximately 24 months
Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs)	DLTs were evaluated according to NCI CTCAE Version 5.0 except CRS, which was graded according to ASTCT Consensus Grading for CRS.	Up to Cycle 1 (each cycle was of 21 days)
Phase 1: Number of Participants With Grade 3 or Higher Treatment Emergent Adverse Events (TEAEs)	AE means any untoward medical occurrence in a participant administered a pharmaceutical product. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product whether or not it is related to the medicinal product. A TEAE was defined as an adverse event which occurred on or after the first dose of study drug and no more than 30 days after the last dose of study drug. A severity grade was evaluated as per the NCI CTCAE Version 5.0, except for CRS, which was assessed by ASTCT Consensus Grading for CRS.	Up to approximately 24 months
Phase 1: Number of Participants With One or More Serious Adverse Events (SAEs)	An SAE is any untoward medical occurrence that results in death; is life-threatening; requires inpatient hospitalization or prolongation of present hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect or is a medically important event that may not be immediately life-threatening or result in death or hospitalization, but may jeopardize the participant or may require intervention to prevent one of other outcomes listed in definition above, or involves suspected transmission via a medicinal product of an infectious agent.

Measure	Description	Time Frame
Phase 1: Cmax: Maximum Observed Plasma Concentration for TAK-981		Cycle 1 (each cycle is 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours)
Phase 1: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-981		Cycle 1 (each cycle is 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Has a histologically or cytologically documented, advanced (metastatic and/or unresectable) cancer as listed below that is incurable: Note: Prior neoadjuvant or adjuvant therapy included in initial treatment may not be considered first- or later-line standard of care treatment unless such treatments were completed less than 12 months prior to the current tumor recurrence.

A. Non-squamous NSCLC for which prior standard first-line treatment containing an anti-programmed cell death protein 1/programmed cell death protein 1 ligand (PD-1/PD-L1) checkpoint inhibitor (CPI) alone or in combination has failed and that has progressed on no more than 1 prior systemic therapy. In Phase 2, participants with nonsquamous NSCLC must have not received more than 1 prior systemic therapy and must not have presented with disease progression during the first 6 months of treatment with first-line CPI/anti-PD-(1/L1)-containing therapy.

Note: In Phase 1, participants with nonsquamous NSCLC and known driver mutations/genomic aberrations (e.g., epidermal growth factor receptor (EGFR), B-Raf proto-oncogene mutation V600E [BRAF V600E], and ROS proto-oncogene 1 [ROS1] sensitizing mutations, neurotrophic receptor tyrosine kinase [NRTK] gene fusions, and anaplastic lymphoma kinase [ALK] rearrangements) must have also shown progressive disease after treatment with a commercially available targeted therapy. In Phase 2, participants with driver mutations are not eligible.

B. CPI-naive cervical cancer (squamous cell carcinoma, adenosquamous carcinoma or adenocarcinoma of the cervix) participants for whom prior standard first-line treatment has failed and who have received no more than 1 prior systemic line of therapy for recurrent or Stage IVB cervical cancer. Note: The following cervical tumors are not eligible: minimal deviation/adenoma malignum, gastric-type adenocarcinoma, clear-cell carcinoma, and mesonephric carcinoma. Histologic confirmation of the original primary tumor is required via pathology report. Note: First-line treatment must have consisted of platinum-containing doublet. Chemotherapy administered concurrently with primary radiation (e.g., weekly cisplatin) is not counted as a systemic chemotherapy regimen.

C. CPI-naïve microsatellite stable-colorectal cancer (MSS-CRC) participants for whom prior standard first-line treatment has failed and who have progressed on no more than 3 chemotherapy regimens.

Note: Participants must have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing regimens if indicated.

D. Unresectable Stage III or Stage IV cutaneous melanoma that has not received prior therapy in the metastatic setting.

Note: Participants with acral melanoma are not eligible. Participants who have presented with disease relapse after ≥6 months of the last dose of CPI or BRAF-mitogen-activated protein kinase kinase (MEK) inhibitor in the adjuvant setting are eligible.

E. Squamous NSCLC for which prior standard first-line treatment containing an anti-PD-(1/L1) checkpoint inhibitor alone or in combination has failed. Participant must have not received more than 1 prior systemic therapy and must not have presented with disease progression during the first 6 months of treatment with first-line CPI/anti-PD-(1/L1)-containing therapy.

F. Squamous or nonsquamous NSCLC for which prior standard first-line treatment containing an anti-PD-(1/L1) checkpoint inhibitor alone or in combination has failed within 6 months from the initiation of the CPI. Participants must not have received more than 1 prior systemic therapy in the metastatic setting.

Note: Participants with driver mutations are not eligible.
Has at least 1 radiologically measurable lesion based on RECIST, Version 1.1. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
Has a performance status of 0 or 1 on the Eastern Cooperative Group Oncology (ECOG) Performance Scale.
Has left ventricular ejection fraction (LVEF) ≥40%; as measured by echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan.
Has recovered to Grade 1 or baseline from all toxicity associated with previous therapy or have the toxicity established as sequela. Note: Has a neuropathy ≤Grade 2, any grade alopecia, or autoimmune endocrinopathies with stable replacement therapy are permitted.
Demonstrate adequate organ function as described below:

A. Platelet count ≥75.0 × 10^9/L. B. Absolute neutrophil count (ANC) ≥1.0 × 10^9/L. C. Hemoglobin ≥85 g/L (red blood cell [RBC] transfusion allowed ≥14 days before assessment).

D. Calculated creatinine clearance ≥30 mL/min using the Cockcroft-Gault formula.

E. Aspartate aminotransferase (AST, GOT) and alanine aminotransferase (ALT, GPT) ≤3.0 times the upper limit of normal (ULN), <5.0 times the ULN if liver enzyme elevations are due to liver metastases; bilirubin ≤1.5 times the ULN. Participants with Gilbert's syndrome may have a bilirubin level >1.5 times the ULN, per discussion between the investigator and the medical monitor.

Exclusion Criteria:

History of uncontrolled brain metastasis (evidence of progression by imaging over a period of 4 weeks and/or neurologic symptoms that have not returned to baseline). Participant with treated brain metastases are allowed provided they are radiologically stable, without evidence of progression for at least 4 weeks by repeat imaging, clinically stable, and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment. Note: For asymptomatic participants, screening brain imaging is not required.
Second malignancy within the previous 3 years, except treated basal cell or localized squamous skin carcinomas, localized prostate cancer, cervical carcinoma in situ, resected colorectal adenomatous polyps, breast cancer in situ, or other malignancy for which the participant is not on active anticancer therapy.
Major surgery ≤14 days from the first dose of study drug and not recovered fully from any complications from surgery.
History of immune-related AEs related to treatment with immune CPIs that required treatment discontinuation.
Receiving or requires the continued use of medications that are known to be strong or moderate inhibitors and inducers of cytochrome P-450 (CYP) 3A4/5 and strong P-glycoprotein (Pgp) inhibitors.
Baseline prolongation of the QT interval corrected using Fridericia's formula (QTcF) (e.g., repeated demonstration of QTcF interval >480 milliseconds (ms), history of congenital long QT syndrome, or torsades de pointes).
Has a history of autoimmune disease requiring systemic immunosuppressive therapy with daily doses of prednisone >10 mg/day or equivalent doses, or any other form of immunosuppressive therapy. Hormone replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for thyroid, adrenal or pituitary insufficiency) for endocrinopathies are not considered prohibited forms of systemic treatment of an autoimmune disease.
Has a history of noninfectious pneumonitis that required steroids or a history of interstitial lung disease.
Has an evidence of active, non-infectious pneumonitis.
Has a history of allogeneic tissue or solid organ transplant.
Has an active infection requiring systemic therapy.
Has a known history of human immunodeficiency virus (HIV) infection or any other relevant congenital or acquired immunodeficiency.
Has a known hepatitis B virus surface antigen seropositive or detectable hepatitis C infection viral load. Note: Participants who have positive hepatitis B core antibody or hepatitis B surface antigen antibody can be enrolled but must have an undetectable hepatitis B viral load.
History of any of the following ≤6 months before first dose: congestive heart failure New York Heart Association Grade III or IV, unstable angina, myocardial infarction, unstable symptomatic ischemic heart disease, uncontrolled hypertension despite appropriate medical therapy, ongoing symptomatic cardiac arrhythmias >Grade 2, pulmonary embolism or symptomatic cerebrovascular events, or any other serious cardiac condition (e.g., pericardial effusion or restrictive cardiomyopathy). Chronic atrial fibrillation on stable anticoagulant therapy is allowed.
Psychiatric illness/social circumstances that would limit compliance with study requirements and substantially increase the risk of AEs or has compromised ability to provide written informed consent.

Name	Affiliation	Role
Medical Director	Takeda	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
HonorHealth		Scottsdale	Arizona	85258	United States
University of California Irvine Medical Center

PubMed Identifier	Type	Citation	Retractions
40373381	Derived	Liu H, Seo S, Joung H. TAK-981 enhances antitumor activity in ELT3 uterine leiomyoma cells through the modulation of apoptosis, cell cycle arrest, and autophagy. Biochem Biophys Res Commun. 2025 Jul 12;770:152000. doi: 10.1016/j.bbrc.2025.152000. Epub 2025 May 12.
35226739	Derived	Nakamura A, Grossman S, Song K, Xega K, Zhang Y, Cvet D, Berger A, Shapiro G, Huszar D. The SUMOylation inhibitor subasumstat potentiates rituximab activity by IFN1-dependent macrophage and NK cell stimulation. Blood. 2022 May 5;139(18):2770-2781. doi: 10.1182/blood.2021014267.

Label	URL
To obtain more information about this study, click this link.	View source

ID	Title	Description
FG000	Dose Escalation: TAK-981 40 mg	Participants received TAK-981 40 mg, intravenous (IV) infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the recommended Phase 2 dose (RP2D) was determined (for a maximum of 24 months).

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jun 22, 2023	Oct 28, 2025

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Phase 1: Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs)

An adverse event (AE) is any untoward medical occurrence in a participant administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. A TEAE is defined as an AE that occurs after administration of first dose of study drug and through 30 days after last dose of study drug or until start of subsequent antineoplastic therapy. AEs were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0 except cytokine release syndrome (CRS), which was graded according to American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading for CRS.

Safety Analysis Set included participants who received at least 1 dose, even if incomplete, of study drug.

Posted

Count of Participants

Participants

Up to approximately 24 months

ID	Title	Description
OG000	Dose Escalation: TAK-981 40 mg	Participants received TAK-981 40 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).
OG001	Dose Escalation: TAK-981 60 mg	Participants received TAK-981 60 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).
OG002	Dose Escalation: TAK-981 90 mg	Participants received TAK-981 90 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).
OG003	Dose Escalation: TAK-981 120 mg	Participants received TAK-981 120 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).

Units	Counts
Participants	OG0003 OG0016 OG00233 OG003

Title

Denominators

Categories

Title	Measurements
	OG0003 OG0016 OG00233 OG003

Primary

Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs)

DLTs were evaluated according to NCI CTCAE Version 5.0 except CRS, which was graded according to ASTCT Consensus Grading for CRS.

The DLT-evaluable Analysis Set included participants enrolled in Phase 1b of the study and who experienced a DLT at any time after receiving the first dose of TAK-981 during the DLT assessment period (Cycle 1) or who received all planned TAK-981 doses and 1 administration of pembrolizumab in Cycle 1.

Posted

Count of Participants

Participants

Up to Cycle 1 (each cycle was of 21 days)

ID	Title	Description
OG000	Dose Escalation: TAK-981 40 mg	Participants received TAK-981 40 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).
OG001	Dose Escalation: TAK-981 60 mg	Participants received TAK-981 60 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).
OG002	Dose Escalation: TAK-981 90 mg

Primary

Phase 1: Number of Participants With Grade 3 or Higher Treatment Emergent Adverse Events (TEAEs)

AE means any untoward medical occurrence in a participant administered a pharmaceutical product. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product whether or not it is related to the medicinal product. A TEAE was defined as an adverse event which occurred on or after the first dose of study drug and no more than 30 days after the last dose of study drug. A severity grade was evaluated as per the NCI CTCAE Version 5.0, except for CRS, which was assessed by ASTCT Consensus Grading for CRS.

Safety Analysis Set included participants who received at least 1 dose, even if incomplete, of study drug.

Posted

Count of Participants

Participants

Up to approximately 24 months

ID	Title	Description
OG000	Dose Escalation: TAK-981 40 mg	Participants received TAK-981 40 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).
OG001	Dose Escalation: TAK-981 60 mg	Participants received TAK-981 60 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).

Primary

Phase 1: Number of Participants With One or More Serious Adverse Events (SAEs)

An SAE is any untoward medical occurrence that results in death; is life-threatening; requires inpatient hospitalization or prolongation of present hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect or is a medically important event that may not be immediately life-threatening or result in death or hospitalization, but may jeopardize the participant or may require intervention to prevent one of other outcomes listed in definition above, or involves suspected transmission via a medicinal product of an infectious agent.

Safety Analysis Set included participants who received at least 1 dose, even if incomplete, of study drug.

Posted

Count of Participants

Participants

Up to approximately 24 months

ID	Title	Description
OG000	Dose Escalation: TAK-981 40 mg	Participants received TAK-981 40 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).
OG001	Dose Escalation: TAK-981 60 mg	Participants received TAK-981 60 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).

Primary

Phase 1: Number of Participants With One or More TEAEs Leading to Dose Modifications and Treatment Discontinuation

An AE is any untoward medical occurrence in a participant administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. A TEAE is defined as an AE that occurs after administration of first dose of study drug and through 30 days after last dose of study drug or until start of subsequent antineoplastic therapy.

Safety Analysis Set included participants who received at least 1 dose, even if incomplete, of study drug.

Posted

Count of Participants

Participants

Up to approximately 24 months

ID	Title	Description
OG000	Dose Escalation: TAK-981 40 mg	Participants received TAK-981 40 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).
OG001	Dose Escalation: TAK-981 60 mg	Participants received TAK-981 60 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).

Primary

Phase 1: Number of Participants With Clinically Significant Laboratory Values

Laboratory parameters included clinical chemistry, hematology, and urinalysis. Participants with at least 1 Grade 3 or 4 Lab Abnormalities were reported.

Safety Analysis Set included participants who received at least 1 dose, even if incomplete, of study drug.

Posted

Count of Participants

Participants

Up to approximately 24 months

ID	Title	Description
OG000	Dose Escalation: TAK-981 40 mg	Participants received TAK-981 40 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).
OG001	Dose Escalation: TAK-981 60 mg	Participants received TAK-981 60 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).
OG002	Dose Escalation: TAK-981 90 mg	Participants received TAK-981 90 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).

Primary

Phase 2: Overall Response Rate (ORR) as Assessed by the Investigator According to RECIST, Version 1.1

ORR is defined as the percentage of participants who achieve Complete Response (CR) and Partial Response (PR) (determined by the investigator) during the study according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.

Response-Evaluable Analysis Set included participants who had received at least 1 dose of study drug, had sites of measurable disease at baseline, and 1 postbaseline disease assessment, or were discontinued due to symptomatic deterioration or death before a postbaseline evaluation happened.

Posted

Number

95% Confidence Interval

percentage of participants

Up to approximately 25 months

ID	Title	Description
OG000	Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 90 mg	Participants with non-squamous NSCLC received TAK-981 90 mg as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.
OG001	Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 120 mg	Participants with non-squamous NSCLC received TAK-981 120 mg as IV infusion on Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

Secondary

Phase 1: Cmax: Maximum Observed Plasma Concentration for TAK-981

Pharmacokinetic (PK) Analysis Set included participants with sufficient dosing and PK data to reliably estimate 1 or more PK parameters. Number of participants analyzed is the number of participants available for analysis during the specified time-point.

Posted

Mean

Standard Deviation

nanograms per milliliter (ng/ml)

Cycle 1 (each cycle is 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours)

ID	Title	Description
OG000	Dose Escalation: TAK-981 40 mg	Participants received TAK-981 40 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).
OG001	Dose Escalation: TAK-981 60 mg	Participants received TAK-981 60 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).
OG002	Dose Escalation: TAK-981 90 mg	Participants received TAK-981 90 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).

Secondary

Phase 1: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-981

PK Analysis Set included participants with sufficient dosing and PK data to reliably estimate 1 or more PK parameters. Number of participants analyzed is the number of participants available for analysis during the specified time-point.

Posted

Median

Full Range

hours

Cycle 1 (each cycle is 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours)

ID	Title	Description
OG000	Dose Escalation: TAK-981 40 mg	Participants received TAK-981 40 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).
OG001	Dose Escalation: TAK-981 60 mg	Participants received TAK-981 60 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).
OG002	Dose Escalation: TAK-981 90 mg	Participants received TAK-981 90 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).

Secondary

Phase 1: AUC0-t: Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for TAK-981

PK Analysis Set included participants with sufficient dosing and PK data to reliably estimate 1 or more PK parameters. Overall number of participants analyzed is the number of participants with data available for analysis. Number of participants analyzed is the number of participants available for analysis during the specified time-point.

Posted

Mean

Standard Deviation

hours*ng/mL

Cycle 1 (each cycle is 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours)

ID	Title	Description
OG000	Dose Escalation: TAK-981 40 mg	Participants received TAK-981 40 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).
OG001	Dose Escalation: TAK-981 60 mg	Participants received TAK-981 60 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).
OG002	Dose Escalation: TAK-981 90 mg

Secondary

Phase 1: AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981

Posted

Mean

Standard Deviation

hours*ng/mL

Cycle 1 (each cycle is 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours)

ID	Title	Description
OG000	Dose Escalation: TAK-981 40 mg	Participants received TAK-981 40 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).
OG001	Dose Escalation: TAK-981 60 mg	Participants received TAK-981 60 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).
OG002	Dose Escalation: TAK-981 90 mg

Secondary

Phase 1: t1/2z: Terminal Disposition Phase Half-life for TAK-981

Posted

Median

Full Range

hours

Cycle 1 (each cycle is 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours)

ID	Title	Description
OG000	Dose Escalation: TAK-981 40 mg	Participants received TAK-981 40 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).
OG001	Dose Escalation: TAK-981 60 mg	Participants received TAK-981 60 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).
OG002	Dose Escalation: TAK-981 90 mg	Participants received TAK-981 90 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).

Secondary

Phase 1: CL: Total Clearance After Intravenous Administration for TAK-981

Posted

Mean

Standard Deviation

liters per hour (L/h)

Cycle 1 (each cycle is 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours)

ID	Title	Description
OG000	Dose Escalation: TAK-981 40 mg	Participants received TAK-981 40 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).
OG001	Dose Escalation: TAK-981 60 mg	Participants received TAK-981 60 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).
OG002	Dose Escalation: TAK-981 90 mg

Secondary

Phase 1: Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-981

Posted

Mean

Standard Deviation

liters (L)

Cycle 1 (each cycle is 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours)

ID	Title	Description
OG000	Dose Escalation: TAK-981 40 mg	Participants received TAK-981 40 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).
OG001	Dose Escalation: TAK-981 60 mg	Participants received TAK-981 60 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).
OG002	Dose Escalation: TAK-981 90 mg

Secondary

Phases 1 and 2: Disease Control Rate (DCR)

DCR is defined as the percentage of participants who achieved stable disease (SD) or better (CR + PR + SD determined by the investigator) >6 weeks during the trial in the response-evaluable population.

Posted

Number

95% Confidence Interval

percentage of participants

Phase 1: Up to approximately 24 months, Phase 2: Up to approximately 25 months

ID	Title	Description
OG000	Dose Escalation: TAK-981 40 mg	Participants received TAK-981 40 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).
OG001	Dose Escalation: TAK-981 60 mg	Participants received TAK-981 60 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).
OG002

Secondary

Phases 1 and 2: Durable Response Rate (DRR)

DRR is defined as the rate of objective responses (CR + PR) maintained for at least 6 months initiating at any time within 12 months of commencing therapy.

Posted

Number

95% Confidence Interval

percentage of participants

Phase 1: Up to approximately 24 months, Phase 2: Up to approximately 25 months

ID	Title	Description
OG000	Dose Escalation: TAK-981 40 mg	Participants received TAK-981 40 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).
OG001	Dose Escalation: TAK-981 60 mg	Participants received TAK-981 60 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).
OG002

Secondary

Phases 1 and 2: Duration of Response (DOR)

DOR is defined as a time from the time of first documentation of tumor response to the first recorded occurrence of disease progression (PD) or death from any cause (whichever occurs first), through end of study.

Posted

Median

95% Confidence Interval

hours

Phase 1: Up to approximately 24 months, Phase 2: Up to approximately 25 months

ID	Title	Description
OG000	Dose Escalation: TAK-981 40 mg	Participants received TAK-981 40 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).
OG001	Dose Escalation: TAK-981 60 mg	Participants received TAK-981 60 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).

Secondary

Phases 1 and 2: Progression-free Survival (PFS)

PFS is defined as time from the date of the first dose administration to the date of first documentation of PD or death due to any cause whichever occurs first, through the end of the study.

Posted

Median

95% Confidence Interval

months

Phase 1: Up to approximately 24 months, Phase 2: Up to approximately 25 months

ID	Title	Description
OG000	Dose Escalation: TAK-981 40 mg	Participants received TAK-981 40 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).
OG001	Dose Escalation: TAK-981 60 mg	Participants received TAK-981 60 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).

Secondary

Phases 1 and 2: Time to Response (TTR)

TTR is defined as time from the date of the first dose administration to the date of first documented PR or better.

Posted

Median

95% Confidence Interval

months

Phase 1: Up to approximately 24 months, Phase 2: Up to approximately 25 months

ID	Title	Description
OG000	Dose Escalation: TAK-981 40 mg	Participants received TAK-981 40 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).
OG001	Dose Escalation: TAK-981 60 mg	Participants received TAK-981 60 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).
OG002

Secondary

Phases 1 and 2: Time to Progression (TTP)

TTP is defined as the from the date of the first dose administration to the date of the first documentation of PD as defined by standard disease criteria.

Posted

Median

95% Confidence Interval

months

Phase 1: Up to approximately 24 months, Phase 2: Up to approximately 25 months

ID	Title	Description
OG000	Dose Escalation: TAK-981 40 mg	Participants received TAK-981 40 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).
OG001	Dose Escalation: TAK-981 60 mg	Participants received TAK-981 60 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).

Secondary

Phase 2: Overall Survival (OS)

OS is defined as the time from the date of the first dose administration to the date of death. Participants without documentation of death at the time of analysis were censored at the date last known to be alive.

Posted

Median

95% Confidence Interval

months

Up to approximately 25 months

ID	Title	Description
OG000	Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 90 mg	Participants with non-squamous NSCLC received TAK-981 90 mg as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.
OG001	Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 120 mg	Participants with non-squamous NSCLC received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

Secondary

Fold Change From Baseline in TAK-981-/Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Peripheral Blood Lymphocytes

The level of TAK-981-SUMO adduct formation was evaluated by flow cytometry as the percentage of adduct formed in peripheral blood lymphocytes. Fold change from baseline was calculated as: Post-treatment value / Baseline value. Positive change denotes improvement.

Pharmacodynamic Analysis Set included participants who provided evaluable blood samples (Cycle 1, Day 1 predose sample and at least 1 postdose sample). Overall number of participants analyzed is the number of participants with data available for analysis. Number of participants analyzed is the number of participants available for analysis during the specified time-point.

Posted

Mean

Standard Deviation

unitless ratio

Cycle 1 Day 1 (1 hour, 4 hours, 8 hours) and Day 8 (Pre-dose, 1 hour, 4 hours and 8 hours) (Cycle length = 21 days)

ID	Title	Description
OG000	Dose Escalation: TAK-981 40 mg	Participants received TAK-981 40 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).
OG001	Dose Escalation: TAK-981 60 mg	Participants received TAK-981 60 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).

Secondary

Fold Change From Baseline in SUMO 2/3 Inhibition in Peripheral Blood Lymphocytes

SUMO pathway inhibition in blood was evaluated by flow cytometry in peripheral blood lymphocytes with an antibody recognizing SUMO 2/3 chains. Fold change from baseline was calculated as: Post-treatment value / Baseline value.

Posted

Mean

Standard Deviation

unitless ratio

Cycle 1 Day 1 (1 hour, 4 hours, 8 hours) and Day 8 (Pre-dose, 1 hour, 4 hours and 8 hours) (Cycle length = 21 days)

ID	Title	Description
OG000	Dose Escalation: TAK-981 40 mg	Participants received TAK-981 40 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).
OG001	Dose Escalation: TAK-981 60 mg	Participants received TAK-981 60 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).

Secondary

Phase 2: Percentage of Participants With One or More Treatment Emergent Adverse Events (TEAEs)

Safety Analysis Set included participants who received at least 1 dose, even if incomplete, of study drug.

Posted

Number

percentage of participants

Up to approximately 25 months

ID	Title	Description
OG000	Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 90 mg	Participants with non-squamous NSCLC received TAK-981 90 mg as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.
OG001	Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 120 mg	Participants with non-squamous NSCLC received TAK-981 120 mg as IV infusion on Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

Secondary

Phase 2: Number of Participants With Grade 3 or Higher Treatment Emergent Adverse Events (TEAEs)

An AE means any untoward medical occurrence in a participant administered a pharmaceutical product. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product whether or not it is related to the medicinal product. A TEAE was defined as an adverse event which occurred on or after the first dose of study drug and no more than 30 days after the last dose of study drug. A severity grade was evaluated as per the NCI CTCAE Version 5.0, except for CRS, which was assessed by ASTCT Consensus Grading for CRS.

Safety Analysis Set included participants who received at least 1 dose, even if incomplete, of study drug.

Posted

Count of Participants

Participants

Up to approximately 25 months

ID	Title	Description
OG000	Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 90 mg	Participants with non-squamous NSCLC received TAK-981 90 mg as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.
OG001	Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 120 mg	Participants with non-squamous NSCLC received TAK-981 120 mg as IV infusion on Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

Secondary

Phase 2: Number of Participants With One or More TEAEs Leading to Dose Modifications and Treatment Discontinuation

Safety Analysis Set included participants who received at least 1 dose, even if incomplete, of study drug.

Posted

Count of Participants

Participants

Up to approximately 25 months

ID	Title	Description
OG000	Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 90 mg	Participants with non-squamous NSCLC received TAK-981 90 mg as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.
OG001	Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 120 mg	Participants with non-squamous NSCLC received TAK-981 120 mg as IV infusion on Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal distension	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG0030 affected19 at risk EG0040 affected14 at risk EG0050 affected9 at risk EG0060 affected21 at risk EG0070 affected9 at risk EG0080 affected28 at risk EG0090 affected15 at risk EG0100 affected4 at risk
Acute myeloid leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Adrenal insufficiency	Endocrine disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Anaemia	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Anaphylactic shock	Immune system disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Aortic aneurysm rupture	Vascular disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Aplasia pure red cell	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected6 at risk EG0020 affected33 at risk EG003
Arrhythmia	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Ascites	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Atrioventricular block	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Biliary obstruction	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Bronchitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Cervix carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Cholangitis acute	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Colorectal cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected6 at risk EG0020 affected33 at risk EG003
Cytokine release syndrome	Immune system disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0023 affected33 at risk EG003
Dermatomyositis	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Device related thrombosis	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Diarrhoea haemorrhagic	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Fatigue	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Gastroenteritis radiation	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected6 at risk EG0020 affected33 at risk EG003
Haematochezia	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Hepatic function abnormal	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Hydronephrosis	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Hypotension	Vascular disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Immune-mediated lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Impaired gastric emptying	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Infected neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Intestinal perforation	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Ischaemic stroke	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Jaundice cholestatic	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Large intestinal obstruction	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0022 affected33 at risk EG003
Malaise	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Malignant biliary obstruction	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Malignant melanoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Malignant neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Mental status changes	Psychiatric disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Metastases to central nervous system	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Metastatic malignant melanoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Non-small cell lung cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Oedema peripheral	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Orchitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Pain	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Pericardial effusion	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected6 at risk EG0020 affected33 at risk EG003
Platelet count decreased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Pleuritic pain	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Pneumonia	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0022 affected33 at risk EG003
Pneumonia bacterial	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Post procedural complication	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Pyrexia	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Sepsis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0022 affected33 at risk EG003
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Spinal cord compression	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Supraventricular tachycardia	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Tracheal obstruction	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Transfusion-related acute lung injury	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Traumatic haemothorax	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal distension	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG0030 affected19 at risk EG0040 affected14 at risk EG0050 affected9 at risk EG0060 affected21 at risk EG0072 affected9 at risk EG0080 affected28 at risk EG0090 affected15 at risk EG0100 affected4 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0023 affected33 at risk EG003
Abdominal pain lower	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0022 affected33 at risk EG003
Abnormal loss of weight	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Abnormal weight gain	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Adrenal insufficiency	Endocrine disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected6 at risk EG0020 affected33 at risk EG003
Agitation	Psychiatric disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0027 affected33 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Anaemia	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected6 at risk EG00216 affected33 at risk EG003
Anaemia of chronic disease	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Anaemia of malignant disease	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Anal fissure	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Angina pectoris	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Angioedema	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Angular cheilitis	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0002 affected3 at risk EG0012 affected6 at risk EG0025 affected33 at risk EG003
Ascites	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG00213 affected33 at risk EG003
Asthenia	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0022 affected33 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Atrial flutter	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected6 at risk EG0023 affected33 at risk EG003
Balance disorder	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Balanitis candida	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Biliary obstruction	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Blood alkaline phosphatase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0025 affected33 at risk EG003
Blood bilirubin increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Blood creatinine increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0023 affected33 at risk EG003
Blood lactate dehydrogenase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Blood pressure increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Blood thyroid stimulating hormone increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Bone disorder	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Brain natriuretic peptide increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Burning sensation	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected6 at risk EG0020 affected33 at risk EG003
C-reactive protein increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
CD4 lymphocytes decreased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
COVID-19	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected6 at risk EG0021 affected33 at risk EG003
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected6 at risk EG0020 affected33 at risk EG003
Cardiac failure	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Cerebrovascular accident	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Cerumen impaction	Ear and labyrinth disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Cheilitis	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Chills	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected6 at risk EG00212 affected33 at risk EG003
Cholangitis	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Chromaturia	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Colon cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected6 at risk EG0023 affected33 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0023 affected33 at risk EG003
Cystitis noninfective	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Cytokine release syndrome	Immune system disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0023 affected33 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG00210 affected33 at risk EG003
Defaecation urgency	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Dengue fever	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Depressed level of consciousness	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Depression	Psychiatric disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Dermatitis	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Dermatitis acneiform	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0022 affected33 at risk EG003
Dermatitis bullous	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Dermatitis psoriasiform	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected6 at risk EG0029 affected33 at risk EG003
Diplopia	Eye disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Dizziness	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Dry eye	Eye disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 affected3 at risk EG0011 affected6 at risk EG0021 affected33 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected6 at risk EG0025 affected33 at risk EG003
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Dysuria	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Early satiety	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Ejection fraction decreased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Electrocardiogram QT prolonged	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Electrocardiogram ST-T segment abnormal	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Epididymal cyst	Reproductive system and breast disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Eye infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Fatigue	General disorders	MedDRA 27.0	Systematic Assessment	EG0002 affected3 at risk EG0011 affected6 at risk EG00213 affected33 at risk EG003
Feeling cold	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Gamma-glutamyltransferase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Gastroenteritis norovirus	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected6 at risk EG0020 affected33 at risk EG003
Gastrointestinal infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
General physical health deterioration	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Haemorrhoidal haemorrhage	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Haemorrhoids	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Hallucination	Psychiatric disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Headache	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected6 at risk EG0026 affected33 at risk EG003
Herpes simplex reactivation	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Herpes zoster	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Hot flush	Vascular disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Hydronephrosis	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0022 affected33 at risk EG003
Hyperphosphataemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Hypertension	Vascular disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Hyperthyroidism	Endocrine disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Hypertransaminasaemia	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Hypertriglyceridaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Hypoaesthesia	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0022 affected33 at risk EG003
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Hypochloraemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0001 affected3 at risk EG0011 affected6 at risk EG0023 affected33 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected6 at risk EG0023 affected33 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0022 affected33 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0022 affected33 at risk EG003
Hypoproteinaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Hypotension	Vascular disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0023 affected33 at risk EG003
Hypothyroidism	Endocrine disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0022 affected33 at risk EG003
Immune-mediated enterocolitis	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Influenza	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Influenza like illness	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0027 affected33 at risk EG003
Infusion site extravasation	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected6 at risk EG0020 affected33 at risk EG003
Ingrowing nail	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Injection site erythema	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Injection site pain	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0022 affected33 at risk EG003
Interleukin level increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Intestinal polyp	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Joint stiffness	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Kidney infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Large intestine polyp	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Leukocytosis	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Leukocyturia	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Leukopenia	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Libido decreased	Psychiatric disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Limb injury	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Lip oedema	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Lipase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Localised oedema	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Lymph node pain	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Lymphocyte count decreased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Lymphopenia	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Malaise	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0024 affected33 at risk EG003
Mouth ulceration	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0001 affected3 at risk EG0011 affected6 at risk EG0021 affected33 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Musculoskeletal stiffness	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0023 affected33 at risk EG003
N-terminal prohormone brain natriuretic peptide increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected6 at risk EG0028 affected33 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Nervous system neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Neutrophil count decreased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0022 affected33 at risk EG003
Night sweats	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected6 at risk EG0020 affected33 at risk EG003
Ocular hyperaemia	Eye disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Odynophagia	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Oedema peripheral	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0022 affected33 at risk EG003
Oral candidiasis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Oral contusion	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Oral herpes	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Orchitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Pain	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0022 affected33 at risk EG003
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Palpitations	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Paronychia	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Parosmia	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Paroxysmal arrhythmia	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Penile oedema	Reproductive system and breast disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Pericardial effusion	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Perineal pain	Reproductive system and breast disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Perioral dermatitis	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Peripheral swelling	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Platelet count decreased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0026 affected33 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Pneumonia	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Polyarthritis	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Polyneuropathy	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Poor peripheral circulation	Vascular disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Procalcitonin increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Proteinuria	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Psoriasis	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Pulpitis dental	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Pyrexia	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected6 at risk EG00217 affected33 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Rash erythematous	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Rash macular	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected6 at risk EG0020 affected33 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0022 affected33 at risk EG003
Rash vesicular	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Rectal haemorrhage	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Renal impairment	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Respiratory tract infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Restless legs syndrome	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
SARS-CoV-2 test positive	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0022 affected33 at risk EG003
Seizure	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Sinus tachycardia	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Sinusitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Skin candida	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Skin infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Somnolence	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Spinal pain	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Steroid diabetes	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0028 affected33 at risk EG003
Supraventricular tachycardia	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Swelling face	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
T-lymphocyte count decreased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Tendon disorder	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Tinea pedis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Tinnitus	Ear and labyrinth disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Tongue ulceration	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Tremor	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Tumour associated fever	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Type 2 diabetes mellitus	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Urethritis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Urinary incontinence	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Urinary retention	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected33 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0024 affected33 at risk EG003
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected6 at risk EG0020 affected33 at risk EG003
Vasculitis	Vascular disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0022 affected33 at risk EG003
Vertigo	Ear and labyrinth disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Viral infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected6 at risk EG0021 affected33 at risk EG003
Viral upper respiratory tract infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected6 at risk EG0020 affected33 at risk EG003
Visual acuity reduced	Eye disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Vitiligo	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected33 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0002 affected3 at risk EG0010 affected6 at risk EG0027 affected33 at risk EG003
Weight decreased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0022 affected33 at risk EG003
White blood cell count decreased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0022 affected33 at risk EG003

ID	Title	Description
BG000	Dose Escalation: TAK-981 40 mg	Participants received TAK-981 40 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).
BG001	Dose Escalation: TAK-981 60 mg	Participants received TAK-981 60 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).
BG002	Dose Escalation: TAK-981 90 mg	Participants received TAK-981 90 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).
BG003	Dose Escalation: TAK-981 120 mg	Participants received TAK-981 120 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).
BG004	Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 90 mg	Participants with non-squamous NSCLC received TAK-981 90 mg as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.
BG005	Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 120 mg	Participants with non-squamous NSCLC received TAK-981 120 mg as IV infusion on Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.
BG006	Dose Expansion: Cohort B: Cervical Cancer TAK-981 90 mg	Participants with cervical cancer received TAK-981 90 mg as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.
BG007	Dose Expansion: Cohort C: MSS-CRC TAK-981 90 mg	Participants with MSS-CRC received TAK-981 90 mg as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.
BG008	Dose Expansion: Cohort D: Cutaneous Melanoma TAK-981 90 mg	Participants with cutaneous melanoma received TAK-981 90 mg as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.
BG009	Dose Expansion: Cohort E: Squamous NSCLC TAK-981 90 mg	Participants with squamous NSCLC received TAK-981 90 mg as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.
BG010	Dose Expansion: Cohort F: CPI Refractory Squamous and Non-squamous NSCLC TAK-981 90 mg	Participants with CPI refractory squamous and non-squamous NSCLC received TAK-981 90 mg as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.
BG011	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Dose Escalation: TAK-981 40 mg	Participants received TAK-981 40 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).	2	3	0	3	3	3
EG001	Dose Escalation: TAK-981 60 mg	Participants received TAK-981 60 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).	2	6	3	6	6	6
EG002	Dose Escalation: TAK-981 90 mg	Participants received TAK-981 90 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).	8	33	17	33	33	33
EG003	Dose Escalation: TAK-981 120 mg	Participants received TAK-981, 120 mg, IV infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months).	4	19	10	19	19	19
EG004	Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 90 mg	Participants with non-squamous NSCLC received TAK-981 90 mg as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.	2	14	3	14	14	14
EG005	Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 120 mg	Participants with non-squamous NSCLC received TAK-981 120 mg as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.	4	9	4	9	9	9
EG006	Dose Expansion: Cohort B: Cervical Cancer TAK-981 90 mg	Participants with cervical cancer received TAK-981 90 mg as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.	9	21	11	21	21	21
EG007	Dose Expansion: Cohort C: MSS-CRC TAK-981 90 mg	Participants with MSS-CRC received TAK-981 90 mg as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.	2	9	4	9	9	9
EG008	Dose Expansion: Cohort D: Cutaneous Melanoma TAK-981 90 mg	Participants with cutaneous melanoma received TAK-981 90 mg as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.	8	28	14	28	28	28
EG009	Dose Expansion: Cohort E: Squamous NSCLC TAK-981 90 mg	Participants with squamous NSCLC received TAK-981 90 mg as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.	2	15	5	15	14	15
EG010	Dose Expansion: Cohort F: CPI Refractory Squamous or Non-squamous NSCLC TAK-981 90 mg	Participants with CPI refractory squamous or non-squamous NSCLC received TAK-981 90 mg as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months.	1	4	3	4	4	4