Study to Assess AFM24 in Advanced Solid Cancers | NCT04259450

NCT04259450

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Phase 1- 14 mg Cohort 1	Experimental	Subjects, with tumors known to express EGFR, who received 14 milligram (mg) AFM24 on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.	Drug: 14 mg AFM24
Phase 1- 40 mg Cohort 2	Experimental	Subjects, with tumors known to express EGFR, who received 40 milligram (mg) AFM24 on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.	Drug: 40 mg AFM24
Phase 1- 80 mg Cohort 3	Experimental	Subjects, with tumors known to express EGFR, who received 80 milligram (mg) AFM24 on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.	Drug: 80 mg AFM24
Phase 1- 160 mg Cohort 4	Experimental	Subjects, with tumors known to express EGFR, who received 160 milligram (mg) AFM24 on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.	Drug: 160 mg AFM24
Phase 1- 320 mg Cohort 5	Experimental	Subjects, with tumors known to express EGFR, who received 320 milligram (mg) AFM24 on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.

Name	Type	Description	Arm Group Labels	Other Names
14 mg AFM24	Drug	14 milligram AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.	Phase 1- 14 mg Cohort 1

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Phase 1: The Number of Subjects With Dose Limiting Toxicities (DLTs) During Cycle 1	The number of patients with dose limiting toxicities (DLTs) in the first cycle, as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0. DLT is defined as an adverse event (AE) or abnormal laboratory value assessed as unrelated to underlying disease, disease progression, inter-current illness, or concomitant medications, that occurs ≤28 days following the first dose of AFM24 (Cycle 1).	During Cycle 1 (up to 28 days)
Phase 2a: Overall Response Rate (Complete Response [CR] + Partial Response [PR])	Overall response as defined by achieving confirmed CR and/or PR assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Partial or complete response needs to be confirmed with repeated assessment at least 4 weeks after the initial assessment.	Up to approximately 16 weeks.

Secondary Outcomes

Measure	Description	Time Frame
Phase 1: The Number of Subjects With Treatment-emergent Adverse Events (TEAEs)	Adverse Events (AEs) will be summarized with patient counts by Medical Dictionary for Regulatory Activities (MedDRA) System Organ Classes (SOCs) and Preferred Terms (PTs).	From the start of first infusion till the last infusion + 30 days, up to approximately 43 weeks.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Adequate organ function
Phase 1: Histologically or cytologically confirmed advanced or metastatic solid malignancies that are known to express EGFR
Phase 1: Previously treated with ≥ 1 lines of anticancer therapy and have documented disease progression during or after their most recent line of anticancer therapy. In addition, either there is no further SOC therapy for the patient or the remaining SOC therapies are deemed not appropriate for the patient by the Investigator.
Phase 1: Patients must have at least one tumor site that is accessible to biopsy
Phase 2a: Measurable disease per RECIST 1.1
Phase 2a: Histologically confirmed advanced or metastatic EGFR+ malignancies for each expansion cohorts:
Colorectal Cancer (MSS), KRAS-wildtype: disease has progressed after ≥ 2 prior lines of therapy which must have included oxaliplatin, fluoropyrimidine, bevacizumab, and an anti-EGFR therapy
ccRCC: disease has progressed after ≥ 2 prior lines of therapy which must have included a TKI and a checkpoint inhibitor
metastatic NSCLC, EGFRmut: disease has progressed on/after after ≥ 1 prior lines of therapy for advanced disease including ≥ 1 prior TKI approved for EGFR mut NSCLC

Exclusion Criteria:

Treatment with systemic anticancer therapy within 4 weeks of the first dose of study drug (6 weeks if therapy was mitomycin C and/or nitrosoureas), or within 5 half-lives of the agent if half-life is known and it is shorter, before first dose of study drug. Anticancer therapies include cytotoxic chemotherapy, targeted inhibitors, and immunotherapies, but do not include hormonal therapy or radiotherapy.
Radiation therapy within 2 weeks before 1st dose of study drug or unresolved toxicity from previous radiotherapy.
History of any other malignancy known to be active, with the exception of completely removed in situ cervical intra-epithelial neoplasia, non-melanoma skin cancer, DCIS, early stage prostate cancer that has been adequately treated, and other cancers from which the patient has been disease free for 3 years or longer.
Currently participating in a study and receiving study therapy, or participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of study treatment.

Name	Affiliation	Role
Michael Emig, MD	Affimed GmbH	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
University of Southern California		Los Angeles	California	90033	United States
Dana Faber Cancer Institute

Arm/Group Information

ID	Title	Description
FG000	Phase 1- 14 mg Cohort 1	Subjects, with tumors known to express EGFR, who received 14 milligram (mg) AFM24 on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.
FG001	Phase 1- 40 mg Cohort 2	Subjects, with tumors known to express EGFR, who received 40 milligram (mg) AFM24 on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.
FG002	Phase 1- 80 mg Cohort 3	Subjects, with tumors known to express EGFR, who received 80 milligram (mg) AFM24 on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.
FG003	Phase 1- 160 mg Cohort 4	Subjects, with tumors known to express EGFR, who received 160 milligram (mg) AFM24 on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.
FG004	Phase 1- 320 mg Cohort 5	Subjects, with tumors known to express EGFR, who received 320 milligram (mg) AFM24 on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.
FG005	Phase 1- 480 mg Cohort 6	Subjects, with tumors known to express EGFR, who received 480 milligram (mg) AFM24 on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.
FG006	Phase 1- 720 mg Cohort 7	Subjects, with tumors known to express EGFR, who received 720 milligram (mg) AFM24 on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle. A dose could be given over two days (split day dosing).
FG007	Phase 2- CRC 480 mg Cohort A	Subjects with microsatellite stable (MSS) colorectal cancer (CRC) with rat sarcoma gene (RAS) wild-type tumor expressing EGFR who received 480 milligram (mg) AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle. A dose could be given over two days (split day dosing).
FG008	Phase 2- ccRCC 480 mg Cohort B	Subjects with clear cell renal cell carcinoma (ccRCC) expressing EGFR who received 480 milligram (mg) AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle. A dose could be given over two days (split day dosing).
FG009	Phase 2- NSCLC 480 mg Cohort C	Subjects with advanced or metastatic (non-small cell lung cancer) NSCLC with an epidermal growth factor receptor (EGFR) mutation who received 480 milligram (mg) AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle. A dose could be given over two days (split day dosing).

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Phase 1- 14 mg Cohort 1	Subjects, with tumors known to express EGFR, who received 14 milligram (mg) AFM24 on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.
BG001	Phase 1- 40 mg Cohort 2

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

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: The Number of Subjects With Dose Limiting Toxicities (DLTs) During Cycle 1

The number of patients with dose limiting toxicities (DLTs) in the first cycle, as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0. DLT is defined as an adverse event (AE) or abnormal laboratory value assessed as unrelated to underlying disease, disease progression, inter-current illness, or concomitant medications, that occurs ≤28 days following the first dose of AFM24 (Cycle 1).

The Dose-Determining Set (DDS): All patients in the safety set (all patients who received at least one dose of AFM24), who had either (a) experienced DLT at any time during Cycle 1, or (b) met the minimum safety evaluation requirements without experiencing DLT within Cycle 1.

Posted

Count of Participants

Participants

During Cycle 1 (up to 28 days)

ID	Title	Description
OG000	Phase 1- 14 mg Cohort 1

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Phase 1- 14 mg Cohort 1	Subjects, with tumors known to express EGFR, who received 14 milligram (mg) AFM24 on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Myocardial infarction	Cardiac disorders	MedDRA version 26.0	Systematic Assessment

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA version 26.0	Systematic Assessment

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jul 26, 2023	Jul 8, 2024	Prot_000.pdf
SAP	No	Yes	No	Statistical Analysis Plan	Jan 27, 2023	Jul 8, 2024	SAP_001.pdf