A Study Evaluating the Safety, Tolerability, Pharmacokine... | NCT04029688

NCT04029688

ID	Type	Description	Link
2018-004579-11	EudraCT Number

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Intervention Names
Dose Escalation: Solid Tumors: Idasanutlin Single Agent	Experimental	Drug: Idasanutlin
Neuroblastoma: Idasanutlin + Venetoclax	Experimental	Drug: Idasanutlin Drug: Venetoclax
Neuroblastoma: Idasanutlin + Cyclophosphamide + Topotecan	Experimental	Drug: Idasanutlin Drug: Cyclophosphamide Drug: Topotecan
AML: Idasanutlin + Venetoclax	Experimental	Drug: Idasanutlin Drug: Venetoclax Drug: Intrathecal Chemotherapy
AML: Idasanutlin + Fludarabine + Cytarabine	Experimental	Drug: Idasanutlin Drug: Fludarabine Drug: Cytarabine Drug: Intrathecal Chemotherapy
ALL: Idasanutlin + Venetoclax	Experimental	Drug: Idasanutlin Drug: Venetoclax Drug: Intrathecal Chemotherapy

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Idasanutlin	Drug	Idasanutlin will be administered as an oral medication once daily on Days 1-5 of a 28-day cycle.	ALL: Idasanutlin + Venetoclax AML: Idasanutlin + Fludarabine + Cytarabine

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Part 1a and 1b: Number of Participants With Adverse Events (AEs) and Severity of AEs Determined According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5 (NCI CTCAE v5.0)	An AE is any untoward medical occurrence in participant administered a pharmaceutical product & regardless of causal relationship with this treatment. An AE can therefore be any unfavorable & unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with use of investigational product, whether or not considered related to investigational product. AEs were graded as per NCI CTCAE v5.0. Grade 1=Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated; Grade 2=Moderate; minimal, local or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living; Grade 3=Severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living; Grade 4=Life-threatening consequences/urgent intervention indicated; Grade 5=Death related to adverse event.	From screening up to 30 days after study treatment discontinuation (approximately 7 months)
Parts 1a and 1b: Number of Participants With Dose-Limiting Toxicities (DLTs)	DLTs were assessed for single-agent idasanutlin and idasanutlin in combination with chemotherapy or venetoclax. A DLT was defined as any AE that occurred during the DLT assessment window and was assessed by the investigator as related or possibly related to idasanutlin. An AE is an untoward medical occurrence in participant administered a pharmaceutical product & regardless of causal relationship with this treatment. Following events were considered to be DLTs: any treatment-related death; elevation of serum hepatic transaminase; severe liver injury, in the absence of cholestasis or other causes of hyperbilirubinemia; any non-hematologic toxicity Grade ≥3; nausea, vomiting, and/or diarrhea if Grade 3 severity lasts > than 24 hours after initiation of supportive care measures or if Grade 4 or higher; hematologic toxicity; any related event that results in a dose delay beyond Day 42.	Cycle 1 (one cycle is 28 days)
Part 1b: Objective Response Rate (ORR) in Participants With TP53 Wild-Type (WT) Neuroblastoma Assessed According to International Neuroblastoma Response Criteria (INRC)

Secondary Outcomes

Measure	Description	Time Frame
Part 1a: Clinical Benefit Rate (CBR) in Participants With Solid Tumors From SE Population Assessed According to Response Evaluation Criteria Version 1.1 (RECIST v1.1) or INRC	CBR was defined as the percentage of participants achieving confirmed CR, PR, or stable disease (SD) on 2 consecutive occasions ≥4 weeks apart during the total study period. Per RECIST, CR was defined as disappearance of all target lesions. PR was defined as at least a 30% decrease in the sum of diameters (SOD) of target lesions, taking as reference the baseline SOD. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference smallest sum on study. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference smallest sum on study (nadir), including baseline. Participants who had neuroblastoma were assessed by INRC. CR and PR per INRC were defined as outlined in the description for Part 1b: ORR outcome measure (OM).

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

The participants ages are < 18 for part 1a, < 30 for Parts 1b. 2 and 3
Study Part 1 (single-agent therapy dose escalation): histologically confirmed diagnosis of neuroblastoma or other solid tumor that has progressed or recurred despite standard therapy, and for which there is no therapy proven to prolong survival with an acceptable quality of life
Study Part 1 (combination safety run-in), Study Part 2 (initial expansion), and Study Part 3 (additional expansion): histologically confirmed diagnosis of neuroblastoma, AML, or precursor-B ALL that has progressed or recurred despite, or is refractory to, standard therapy
Adequate performance status: Participants <16 years of age: Lansky greater than or equal to (≥)50%; Patients ≥16 years of age: Karnofsky ≥50%
Adequate end-organ function, as defined in the protocol
For females of childbearing potential: agreement to remain abstinent, use contraception, agreement to refrain from donating eggs. Females must remain abstinent or use two methods of contraception with a failure rate of <1% per year during the treatment and follow-up period (variable depending on the combination agent) or in accordance with national prescribing information guidance regarding abstinence, contraception
For males: agreement to remain abstinent or use a condom, and agreement to refrain from donating sperm, with a female partner of childbearing potential or pregnant female partner, males must remain abstinent or use a condom during the treatment period and for follow-up period (variable, depending on the combination agent) or in accordance with national prescribing information guidance regarding abstinence, contraception

Additional Inclusion Criteria for Participants with Solid Tumors (including Neuroblastoma)

At least one evaluable or measurable radiological site of disease as defined by standard criteria for the participant's tumor type, or measurable bone marrow disease by morphology
Adequate hematologic end-organ function, as defined in the protocol
Tumor tissue from relapsed disease

Additional Inclusion Criteria for Patients with Leukemia

Bone marrow with ≥5% lymphoblasts by morphologic assessment at screening
Available bone marrow aspirate or biopsy from screening

Exclusion Criteria:

Primary Central Nervous System (CNS) tumors
Symptomatic CNS metastases that result in a neurologically unstable clinical state or require increasing doses of corticosteroids or local CNS-directed therapy to control the CNS disease
CNS3 leukemia
Acute promyelocytic leukemia
White blood cell count >50 × 10^9 cells/Liter (L)
Down syndrome, Li-Fraumeni syndrome, history of severe aplastic anemia, or any known bone marrow failure predisposition syndrome
Burkitt-type acute lymphoblastic leukemia
T-cell lymphoblastic leukemia
Prior treatment with a MDM2 antagonist
Prior treatment with venetoclax (if potential for enrollment in a venetoclax arm)
Infection considered by the investigator to be clinically uncontrolled or of unacceptable risk to the participant
Any uncontrolled medical condition or other identified abnormality that precludes the patient's safe participation in and completion of the study
Systemic anticancer therapy within 28 days or 5 half-lives, whichever is shorter, prior to initiation of study treatment
Treatment with monoclonal antibodies, antibody drug conjugates, or cellular therapy for anti-neoplastic intent within 30 days prior to initiation of study treatment
I-131 meta-iodobenzylguanidine (MIBG) therapy within 6 weeks prior to initiation of study treatment
Myeloablative therapy with autologous or allogeneic hematopoietic stem cell rescue within 100 days of study treatment initiation
Immunosuppressive therapy for treatment of graft-versus-host disease within 2 weeks of study treatment initiation
Radiotherapy within 3 weeks prior to study treatment initiation
Specific restrictions are applicable for patients treated with drugs interacting with CYP2C8, CYP3A4, OATP1B1/B3, and P-gp
Received anti-coagulant or anti-platelet agent within 7 days or 5 half-lives prior to study treatment initiation
Underwent major surgical procedure within 21 days of study treatment initiation, or anticipate need for major surgical procedure during the course of the study

Contacts/Locations Module

Name	Affiliation	Role
Clinical Trials	Hoffmann-La Roche	Study Director

Locations

Facility	Status	City	State	ZIP	Country	Contacts
Arkansas Children's Hospital Research Institute		Little Rock	Arkansas	72202	United States
Lucile Packard Children's Hospital at Stanford University; Thoracic Oncology

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
41379293	Derived	Rubio-San-Simon A, Marshall LV, Doz F, Mora J, Bielamowicz K, Corradini N, Langevin AM, Narendran A, Smith AA, Zwaan CM, Gho D, Cardenas A, Fowler S, Guizani C, Breton V, Wulff B, Bernardi R, Trippett T, Campbell-Hewson Q. Idasanutlin in Combination with Chemotherapy or Venetoclax in Pediatric and Young Adult Patients with Relapsed/Refractory Solid Tumors (iMATRIX Idasa): Results of a Phase I/II, Multicenter, Multi-arm Study. Target Oncol. 2026 Jan;21(1):87-102. doi: 10.1007/s11523-025-01186-w. Epub 2025 Dec 11.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Part 1a: Idasanutlin 2 Milligrams/Kilograms (mg/kg)	Participants with solid tumors received idasanutlin 2 mg/kg orally once daily (QD) on Days 1-5 of each 28-day cycle until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.
FG001

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Mar 19, 2021

Derived Section

Miscellaneous Info Module

Submission Tracking

Condition Browse Module

Intervention Browse Module

Masking Info

AML: Idasanutlin + Venetoclax

Dose Escalation: Solid Tumors: Idasanutlin Single Agent

Neuroblastoma: Idasanutlin + Cyclophosphamide + Topotecan

Neuroblastoma: Idasanutlin + Venetoclax

Intent-to-Treat (ITT) population included all enrolled participants in the study, regardless of whether they were dosed.

Arm/Group Information

ID	Title	Description
BG000	Part 1a: Idasanutlin 2 mg/kg	Participants with solid tumors received idasanutlin 2 mg/kg QD on Days 1-5 of each 28-day cycle until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.
BG001	Part 1a: Idasanutlin 3 mg/kg	Participants with solid tumors received idasanutlin 3 mg/kg orally QD on Days 1-5 of each 28-day cycle until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.
BG002	Part 1a: Idasanutlin 4.5 mg/kg	Participants with solid tumors received idasanutlin 4.5 mg/kg orally QD on Days 1-5 of each 28-day cycle until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.
BG003	Part 1a: Idasanutlin 6.4 mg/kg	Participants with solid tumors received idasanutlin 6.4 mg/kg orally QD on Days 1-5 of each 28-day cycle until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.
BG004	Part 1a: Idasanutlin 8 mg/kg	Participants with solid tumors received idasanutlin 8 mg/kg orally QD on Days 1-5 of each 28-day cycle until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.
BG005	Part 1b: Idasanutlin (2.8 mg/kg) +Chemotherapy	Participants with neuroblastoma received idasanutlin 2.8 mg/kg orally in combination with cyclophosphamide 200 mg/m^2 and topotecan 0.6 mg/m^2 as an IV infusion QD on Days 1-5 of each 28-day cycle. Treatment was administered until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.
BG006	Part 1b: Idasanutlin (3.6 mg/kg) +Chemotherapy	Participants with neuroblastoma received idasanutlin, 3.6 mg/kg orally, in combination with cyclophosphamide 250 mg/m^2 and topotecan 0.75 mg/m^2 as an IV infusion QD on Days 1-5 of each 28-day cycle. Treatment was administered until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.
BG007	Part 1b: Idasanutlin (3.6mg/kg) + Venetoclax	Participants with neuroblastoma (first 3) received idasanutlin, 3.6 mg/kg orally QD on Days 1-5, in combination with venetoclax 400 mg adult dose equivalent (adjusted by body weight) on Days 1-28 of each 28-day cycle. After the first three participants were treated, the schedule was modified as idasanutlin, 3.6 mg/kg orally QD on Days 1-5 and venetoclax 400 mg (adult dose equivalent) on Days 1-14 of a each 28-day cycle for the next 3 participants enrolled in this arm. Treatment was administered until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.
BG008	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG0007.6± 5.0 BG00111.3± 3.2 BG0027.3± 3.9 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0005 BG0011 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0002 BG0011 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

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

Part 1a and 1b: Number of Participants With Adverse Events (AEs) and Severity of AEs Determined According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5 (NCI CTCAE v5.0)

An AE is any untoward medical occurrence in participant administered a pharmaceutical product & regardless of causal relationship with this treatment. An AE can therefore be any unfavorable & unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with use of investigational product, whether or not considered related to investigational product. AEs were graded as per NCI CTCAE v5.0. Grade 1=Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated; Grade 2=Moderate; minimal, local or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living; Grade 3=Severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living; Grade 4=Life-threatening consequences/urgent intervention indicated; Grade 5=Death related to adverse event.

Safety evaluable (SE) population included all participants who received any amount of the study treatment, whether prematurely withdrawn from the study or not.

Posted

Count of Participants

Participants

From screening up to 30 days after study treatment discontinuation (approximately 7 months)

ID	Title	Description
OG000	Part 1a: Idasanutlin 2 mg/kg	Participants with solid tumors received idasanutlin 2 mg/kg QD on Days 1-5 of each 28-day cycle until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.
OG001	Part 1a: Idasanutlin 3 mg/kg	Participants with solid tumors received idasanutlin 3 mg/kg orally QD on Days 1-5 of each 28-day cycle until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.
OG002	Part 1a: Idasanutlin 4.5 mg/kg	Participants with solid tumors received idasanutlin 4.5 mg/kg orally QD on Days 1-5 of each 28-day cycle until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.
OG003	Part 1a: Idasanutlin 6.4 mg/kg	Participants with solid tumors received idasanutlin 6.4 mg/kg orally QD on Days 1-5 of each 28-day cycle until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.
OG004	Part 1a: Idasanutlin 8 mg/kg	Participants with solid tumors received idasanutlin 8 mg/kg orally QD on Days 1-5 of each 28-day cycle until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.
OG005	Part 1b: Idasanutlin (2.8mg/kg) +Chemotherapy	Participants with neuroblastoma received idasanutlin 2.8 mg/kg orally in combination with cyclophosphamide 200 mg/m^2 and topotecan 0.6 mg/m^2 as an IV infusion QD on Days 1-5 of each 28-day cycle. Treatment was administered until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.

Units	Counts
Participants	OG0008 OG0013 OG0026 OG003

Title

Denominators

Categories

AEs, Any Grade

Title	Measurements
	OG0008 OG0013 OG0026 OG003

Primary

Parts 1a and 1b: Number of Participants With Dose-Limiting Toxicities (DLTs)

DLTs were assessed for single-agent idasanutlin and idasanutlin in combination with chemotherapy or venetoclax. A DLT was defined as any AE that occurred during the DLT assessment window and was assessed by the investigator as related or possibly related to idasanutlin. An AE is an untoward medical occurrence in participant administered a pharmaceutical product & regardless of causal relationship with this treatment. Following events were considered to be DLTs: any treatment-related death; elevation of serum hepatic transaminase; severe liver injury, in the absence of cholestasis or other causes of hyperbilirubinemia; any non-hematologic toxicity Grade ≥3; nausea, vomiting, and/or diarrhea if Grade 3 severity lasts > than 24 hours after initiation of supportive care measures or if Grade 4 or higher; hematologic toxicity; any related event that results in a dose delay beyond Day 42.

DLT-evaluable population included all participants enrolled in Part 1 who either completed at least 80% of the prescribed dose of idasanutlin and the DLT observation window in Cycle 1 OR have experienced a DLT in Cycle 1 of the dose-escalation phase.

Posted

Count of Participants

Participants

Cycle 1 (one cycle is 28 days)

ID	Title	Description
OG000	Part 1a: Idasanutlin 2 mg/kg	Participants with solid tumors received idasanutlin 2 mg/kg QD on Days 1-5 of each 28-day cycle until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.
OG001

Primary

Part 1b: Objective Response Rate (ORR) in Participants With TP53 Wild-Type (WT) Neuroblastoma Assessed According to International Neuroblastoma Response Criteria (INRC)

ORR was defined as the percentage of participants with complete response (CR) or partial response (PR) at any time during study treatment, on 2 consecutive occasions ≥ 4 weeks apart, as determined by the investigator per INRC. Primary tumor: CR = <10 millimeters (mm) residual soft tissue at primary site and complete resolution of meta-iodobenzylguanidine (MIBG) or fluorodeoxyglucose-positron emission tomography (FDG-PET) uptake at primary site. PR = ≥ 30% decrease in longest diameter of primary site and MIBG or FDG-PET uptake at primary site stable, improved, or resolved. Soft tissue & bone metastases: CR = resolution of all disease sites; PR = ≥30% decrease in sum of non-primary target lesions, with no new lesions or ≥50% reduction in MIBG score or in number of FDG-PET-avid bone lesions; Bone marrow: CR = no tumor infiltration on reassessment.

Participants in the SE population who had TP53 WT tumor as assessed by central testing were analyzed for this outcome measure. SE Population included all participants who received any amount of the study treatment, whether prematurely withdrawn from the study or not. Percentages have been rounded off to the nearest decimal point.

Posted

Number

95% Confidence Interval

percentage of participants

From screening (maximum 28 days) up to Cycle 6 (cycle length=28 days)

ID	Title	Description
OG000	Part 1b: Idasanutlin (2.8mg/kg) +Chemotherapy	Participants with neuroblastoma received idasanutlin 2.8 mg/kg orally in combination with cyclophosphamide 200 mg/m^2 and topotecan 0.6 mg/m^2 as an IV infusion QD on Days 1-5 of each 28-day cycle. Treatment was administered until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.

Primary

Parts 2 and 3: ORR in Participants With TP53 WT Neuroblastoma Assessed According to INRC

ORR was defined as the percentage of participants with CR or PR at any time during study treatment, on 2 consecutive occasions ≥ 4 weeks apart, as determined by the investigator per INRC. Primary tumor: CR = <10 mm residual soft tissue at primary site and complete resolution of MIBG or FDG-PET uptake at primary site. PR = ≥ 30% decrease in longest diameter of primary site and MIBG or FDG-PET uptake at primary site stable, improved, or resolved. Soft tissue & bone metastases: CR = resolution of all disease sites; PR = ≥30% decrease in sum of non-primary target lesions, with no new lesions or ≥50% reduction in MIBG score or in number of FDG-PET-avid bone lesions; Bone marrow: CR = no tumor infiltration on reassessment.

The study was terminated before initiation of Parts 2 and 3 as per sponsor's decision. Hence no data were collected, and this outcome measure was not assessed or analyzed.

Posted

Up to approximately 29 months

ID	Title	Description
OG000	Part 2 (Neuroblastoma)	Participants with neuroblastoma were planned to be enrolled in various cohorts in Part 2. Participants with neuroblastoma were to receive idasanutlin in combination with cyclophosphamide 250 mg/m^2 and topotecan 0.75 mg/m^2 on Days 1-5 of each 28-day cycle or venetoclax 400 mg.
OG001	Part 3: Expansion (Neuroblastoma)	Potential expansion of idasanutlin combination cohorts for participants with TP53 WT neuroblastoma from Parts 1b and 2 meeting the pre-defined efficacy criteria were planned to be initiated in Part 3.

Primary

Parts 2 and 3: Complete Remission Rate (CRR) in Participants With TP53 WT Leukemia

CRR was defined as the percentage of participants with morphologic complete remission (CR), complete remission with incomplete blood count recovery (CRi), or complete remission with incomplete platelet count recovery (CRp) within 2 cycles of study treatment. CR=Bone marrow blasts <5% (AML) and no evidence of circulating blasts, must be <1% (ALL); absence of blasts with Auer rods (AML); absence of extramedullary disease; absolute neutrophil count (ANC) >1.0*10^9/liter (L) [1000/microliter (µL)]; platelet count > 100*10^9/L (100,000/µL); independence of transfusions for a minimum of 1 week (AML and ALL). CRi= All CR criteria except for ANC <1.0*10^9/L[1000/µL] or insufficient recovery of platelet count <100* 10^9/L [100,000/µL] (AML and ALL). CRp=All CR criteria except for ANC >1.0*10^9/L[1000/µL]) or but with insufficient recovery of platelet (<100* 10^9/L [100,000/µL]) (ALL).

The study was terminated before initiation of Parts 2 and 3 as per sponsor's decision. Hence no data were collected, and this outcome measure was not assessed or analyzed.

Posted

Up to Cycle 2 (cycle length=28 days) (approximately 8 weeks)

ID	Title	Description
OG000	Part 2 (Leukemia)	Participants with acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) were planned to be enrolled in various cohorts in Part 2. Participants with AML were to receive idasanutlin plus fludarabine 30 mg/m^2 and high dose cytarabine 2000 mg/m^2 (FLA) on Days 1-5 of each 28-day cycle. Participants with ALL were to receive idasanutlin plus venetoclax 600 mg on Days 1-5 of each 28-day cycle.

Primary

Parts 2 and 3: Minimal Residual Disease (MRD) - Negative Rate in Participants With ALL

MRD - negative rate was defined as percentage of participants with ALL who have an MRD value < 0.01%, as measured by next-generation sequencing (NGS), within 2 cycles of study treatment.

The study was terminated before initiation of Parts 2 and 3 as per sponsor's decision. Hence no data were collected, and this outcome measure was not assessed or analyzed.

Posted

Up to Cycle 2 (cycle length=28 days) (approximately 8 weeks)

ID	Title	Description
OG000	Part 2 (ALL)	Participants with ALL were planned to be enrolled in Part 2 to receive idasanutlin plus venetoclax 600 mg on Days 1-5 of each 28-day cycle.
OG001	Part 3: Expansion (ALL)	Potential expansion of idasanutlin combination cohorts for participants with TP35 WT ALL from Parts 1b and 2 meeting the pre-defined efficacy criteria were planned to be initiated in Part 3.

Units	Counts
Participants

Secondary

Part 1a: Clinical Benefit Rate (CBR) in Participants With Solid Tumors From SE Population Assessed According to Response Evaluation Criteria Version 1.1 (RECIST v1.1) or INRC

CBR was defined as the percentage of participants achieving confirmed CR, PR, or stable disease (SD) on 2 consecutive occasions ≥4 weeks apart during the total study period. Per RECIST, CR was defined as disappearance of all target lesions. PR was defined as at least a 30% decrease in the sum of diameters (SOD) of target lesions, taking as reference the baseline SOD. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference smallest sum on study. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference smallest sum on study (nadir), including baseline. Participants who had neuroblastoma were assessed by INRC. CR and PR per INRC were defined as outlined in the description for Part 1b: ORR outcome measure (OM).

SE population included all participants who received any amount of the study treatment, whether prematurely withdrawn from the study or not. Percentages have been rounded off to the nearest decimal point.

Posted

Number

95% Confidence Interval

percentage of participants

From screening (maximum 28 days) up to Cycle 5 (cycle length=28 days)

ID	Title	Description
OG000	Part 1a: Idasanutlin 2 mg/kg	Participants with solid tumors received idasanutlin 2 mg/kg QD on Days 1-5 of each 28-day cycle until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.

Secondary

Part 1b: CBR in Participants With Neuroblastoma From SE Population Assessed According to INRC

CBR=percentage of participants with CR, PR, or SD on 2 consecutive occasions ≥ 4 weeks apart per INRC. Primary tumor: CR=residual soft tissue at primary site is <10 mm, with complete resolution of MIBG/FDG-PET uptake; PR= ≥30% decrease in longest diameter (LD) of primary site, with stable/improved MIBG/FDG-PET uptake; SD=Insufficient shrinkage for PR/increase for PD. PD= >20% increase in LD from smallest sum & minimum 5 mm increase in LD. Soft tissue & bone metastases: CR=resolution of all disease sites; PR= ≥30% decrease in sum of non-primary target lesions, with no new lesions or ≥50% reduction in MIBG score or in number of FDG-PET-avid bone lesions; PD=new soft tissue lesions per CT/MRI or MIBG/FDG-PET avid bone site; SD=no sufficient change in non-primary lesions. Bone marrow: CR=no tumor infiltration on reassessment; PD=new tumor infiltration >5% or infiltration increased >2-fold with >20% tumor infiltration; SD=persistent infiltration at >5% without meeting other criteria.

Posted

Number

95% Confidence Interval

percentage of participants

From screening (maximum 28 days) up to Cycle 6 (cycle length=28 days)

ID	Title	Description
OG000	Part 1b: Idasanutlin (2.8mg/kg) +Chemotherapy	Participants with neuroblastoma received idasanutlin 2.8 mg/kg orally in combination with cyclophosphamide 200 mg/m^2 and topotecan 0.6 mg/m^2 as an IV infusion QD on Days 1-5 of each 28-day cycle. Treatment was administered until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.

Secondary

Part 1b: CBR in Participants With TP53 WT Neuroblastoma Assessed According to INRC

CBR=percentage of participants with CR, PR, or SD on 2 consecutive occasions ≥ 4 weeks apart per INRC. Primary tumor: CR=residual soft tissue at primary site is <10 mm, with complete resolution of MIBG/FDG-PET uptake; PR= ≥30% decrease in longest diameter (LD) of primary site, with stable/improved MIBG/FDG-PET uptake; SD=Insufficient shrinkage for PR or increase for PD. PD= >20% increase in LD from smallest sum & minimum 5 mm increase in LD. Soft tissue & bone metastases: CR=resolution of all disease sites; PR= ≥30% decrease in sum of non-primary target lesions, with no new lesions or ≥50% reduction in MIBG score or in number of FDG-PET-avid bone lesions; PD=new soft tissue lesions per CT/MRI or MIBG/FDG-PET avid bone site; SD=no sufficient change in non-primary lesions. Bone marrow: CR=no tumor infiltration on reassessment; PD=new tumor infiltration >5% or infiltration increased >2-fold with >20% tumor infiltration; SD=persistent infiltration at >5% without meeting other criteria.

Posted

Number

95% Confidence Interval

percentage of participants

From screening (maximum 28 days) up to Cycle 6 (cycle length=28 days)

ID	Title	Description
OG000	Part 1b: Idasanutlin (2.8mg/kg) +Chemotherapy	Participants with neuroblastoma received idasanutlin 2.8 mg/kg orally in combination with cyclophosphamide 200 mg/m^2 and topotecan 0.6 mg/m^2 as an IV infusion QD on Days 1-5 of each 28-day cycle. Treatment was administered until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.

Secondary

Part 1a: Duration of Response (DOR) in Participants With Solid Tumors From SE Population Assessed According to RECIST v1.1 or INRC

DOR was defined as the time from the first tumor assessment that supports a participant's objective response (CR or PR) to the time of PD or death from any cause (whichever occurs first), as determined by the investigator using RECIST v1.1 or INRC. Per PRECIST, CR was defined as disappearance of all target lesions. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference smallest sum on study (nadir), including baseline. Participants who had neuroblastoma were assessed by INRC. CR/PR/PD were defined per INRC as outlined in the description for the Part 1b: CBR OM.

SE population included all participants who received any amount of the study treatment, whether prematurely withdrawn from the study or not. DOR was only evaluated in participants who achieved an objective response (CR or PR).

Posted

From screening (maximum 28 days) up to Cycle 5 (cycle length=28 days)

ID	Title	Description
OG000	Part 1a: Idasanutlin 2 mg/kg	Participants with solid tumors received idasanutlin 2 mg/kg QD on Days 1-5 of each 28-day cycle until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.
OG001	Part 1a: Idasanutlin 3 mg/kg	Participants with solid tumors received idasanutlin 3 mg/kg orally QD on Days 1-5 of each 28-day cycle until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.

Secondary

Part 1b: DOR in Participants With Neuroblastoma From SE Population Assessed According to INRC

DOR=time from the first tumor assessment that supports a participant's objective response (CR or PR) to the time of PD or death from any cause (whichever occurs first), as determined by the investigator using INRC for participants with neuroblastoma. Primary tumor: CR=residual soft tissue at primary site is <10 mm, with complete resolution of MIBG/FDG-PET uptake; PR= ≥30% decrease in LD of primary site and MIBG or FDG-PET uptake at primary site stable, improved, or resolved; PD= >20% increase in LD from smallest sum & minimum 5 mm increase in LD. Soft tissue & bone metastases: CR = resolution of all disease sites; PR = ≥30% decrease in sum of non-primary target lesions, with no new lesions or ≥50% reduction in MIBG score or in number of FDG-PET-avid bone lesions; PD=new soft tissue lesions per CT/MRI or MIBG/FDG-PET avid bone site. Bone marrow: CR=no tumor infiltration on reassessment; PD=new tumor infiltration >5% or infiltration increased >2-fold with >20% tumor infiltration.

Posted

Median

95% Confidence Interval

months

From screening (maximum 28 days) up to Cycle 6 (cycle length=28 days)

ID	Title	Description
OG000	Part 1b: Idasanutlin (2.8mg/kg) +Chemotherapy	Participants with neuroblastoma received idasanutlin 2.8 mg/kg orally in combination with cyclophosphamide 200 mg/m^2 and topotecan 0.6 mg/m^2 as an IV infusion QD on Days 1-5 of each 28-day cycle. Treatment was administered until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.

Secondary

Part 1b: DOR in in Participants With TP53 WT Neuroblastoma Assessed According to INRC

Participants in the SE population who had TP53 WT tumor as assessed by central testing were analyzed for this outcome measure. SE Population included all participants who received any amount of the study treatment, whether prematurely withdrawn from the study or not. DOR was only evaluated in participants who achieved an objective response (CR or PR).

Posted

Median

95% Confidence Interval

months

From screening (maximum 28 days) up to Cycle 6 (cycle length=28 days)

ID	Title	Description
OG000	Part 1b: Idasanutlin (2.8mg/kg) +Chemotherapy	Participants with neuroblastoma received idasanutlin 2.8 mg/kg orally in combination with cyclophosphamide 200 mg/m^2 and topotecan 0.6 mg/m^2 as an IV infusion QD on Days 1-5 of each 28-day cycle. Treatment was administered until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.

Secondary

Part 1a: Progression Free Survival (PFS) in Participants With Solid Tumors From SE Population Assessed According to RECIST v1.1 or INRC

PFS was defined as the time from initiation of study drug to the first documented occurrence of PD or death from any cause (whichever occurs first), as determined by the investigator using RECIST or INRC. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference smallest sum on study (nadir), including baseline. Participants who had neuroblastoma were assessed by INRC. PD per INRC: Primary tumor = >20% increase in LD from smallest sum & minimum 5 mm increase in LD; Soft tissue & bone metastases = new soft tissue lesions per CT/MRI or MIBG/FDG-PET avid bone site; Bone marrow = new tumor infiltration >5% or infiltration increased >2-fold with >20% tumor infiltration.

SE population included all participants who received any amount of the study treatment, whether prematurely withdrawn from the study or not.

Posted

Median

95% Confidence Interval

months

From screening (maximum 28 days) up to Cycle 5 (cycle length=28 days)

ID	Title	Description
OG000	Part 1a: Idasanutlin 2 mg/kg	Participants with solid tumors received idasanutlin 2 mg/kg QD on Days 1-5 of each 28-day cycle until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.
OG001	Part 1a: Idasanutlin 3 mg/kg	Participants with solid tumors received idasanutlin 3 mg/kg orally QD on Days 1-5 of each 28-day cycle until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.

Secondary

Part 1b: PFS in Participants With Neuroblastoma From SE Population Assessed According to INRC

PFS was defined as the time from initiation of study drug to the first documented occurrence of PD or death from any cause (whichever occurs first), as determined by the investigator using INRC for participants with neuroblastoma. Primary tumor: PD= >20% increase in LD from smallest sum & minimum 5 mm increase in LD. Soft tissue & bone metastases: PD=new soft tissue lesions per CT/MRI or MIBG/FDG-PET avid bone site. Bone marrow: PD=new tumor infiltration >5% or infiltration increased >2-fold with >20% tumor infiltration.

SE population included all participants who received any amount of the study treatment, whether prematurely withdrawn from the study or not.

Posted

Median

95% Confidence Interval

months

From screening (maximum 28 days) up to Cycle 6 (cycle length=28 days)

ID	Title	Description
OG000	Part 1b: Idasanutlin (2.8mg/kg) +Chemotherapy	Participants with neuroblastoma received idasanutlin 2.8 mg/kg orally in combination with cyclophosphamide 200 mg/m^2 and topotecan 0.6 mg/m^2 as an IV infusion QD on Days 1-5 of each 28-day cycle. Treatment was administered until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.
OG001	Part 1b: Idasanutlin (3.6mg/kg) +Chemotherapy	Participants with neuroblastoma received idasanutlin, 3.6 mg/kg orally, in combination with cyclophosphamide 250 mg/m^2 and topotecan 0.75 mg/m^2 as an IV infusion QD on Days 1-5 of each 28-day cycle. Treatment was administered until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.

Secondary

Part 1b: PFS in Participants With TP53 WT Neuroblastoma Assessed According to INRC

PFS was defined as the time from initiation of study drug to the first documented occurrence of PD or death from any cause (whichever occurs first), as determined by the investigator using INRC for participants with neuroblastoma. Primary tumor: PD= >20% increase in LD from smallest sum & minimum 5 mm increase in LD. Soft tissue & bone metastases: PD=new soft tissue lesions per CT/MRI or MIBG/FDG-PET avid bone site. Bone marrow: PD=new tumor infiltration >5% or infiltration increased >2-fold with >20% tumor infiltration.

Posted

Median

95% Confidence Interval

months

From screening (maximum 28 days) up to Cycle 6 (cycle length=28 days)

ID	Title	Description
OG000	Part 1b: Idasanutlin (2.8mg/kg) +Chemotherapy	Participants with neuroblastoma received idasanutlin 2.8 mg/kg orally in combination with cyclophosphamide 200 mg/m^2 and topotecan 0.6 mg/m^2 as an IV infusion QD on Days 1-5 of each 28-day cycle. Treatment was administered until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.
OG001	Part 1b: Idasanutlin (3.6mg/kg) +Chemotherapy

Secondary

Parts 1a and 1b: Overall Survival (OS) in SE Population

OS was defined as the time from initiation of the study drug to death from any cause. Estimates for median OS were computed using Kaplan-Meier methodology

SE population included all participants who received any amount of the study treatment, whether prematurely withdrawn from the study or not.

Posted

Median

95% Confidence Interval

months

Up to approximately 29 months

ID	Title	Description
OG000	Part 1a: Idasanutlin 2 mg/kg	Participants with solid tumors received idasanutlin 2 mg/kg QD on Days 1-5 of each 28-day cycle until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.
OG001	Part 1a: Idasanutlin 3 mg/kg	Participants with solid tumors received idasanutlin 3 mg/kg orally QD on Days 1-5 of each 28-day cycle until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.
OG002	Part 1a: Idasanutlin 4.5 mg/kg	Participants with solid tumors received idasanutlin 4.5 mg/kg orally QD on Days 1-5 of each 28-day cycle until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.

Secondary

Part 1b: OS in Participants With TP53 WT Neuroblastoma

OS was defined as the time from initiation of the study drug to death from any cause. Estimates for median OS were computed using Kaplan-Meier methodology

Posted

Median

95% Confidence Interval

months

Up to approximately 29 months

ID	Title	Description
OG000	Part 1b: Idasanutlin (2.8mg/kg) +Chemotherapy	Participants with neuroblastoma received idasanutlin 2.8 mg/kg orally in combination with cyclophosphamide 200 mg/m^2 and topotecan 0.6 mg/m^2 as an IV infusion QD on Days 1-5 of each 28-day cycle. Treatment was administered until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.
OG001	Part 1b: Idasanutlin (3.6mg/kg) +Chemotherapy	Participants with neuroblastoma received idasanutlin, 3.6 mg/kg orally, in combination with cyclophosphamide 250 mg/m^2 and topotecan 0.75 mg/m^2 as an IV infusion QD on Days 1-5 of each 28-day cycle. Treatment was administered until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.

Secondary

Part 1a: ORR Irrespective of TP53 Status in Participants With Solid Tumor From SE Population According to RECIST v1.1 or INRC

ORR was defined as the percentage of participants with CR or PR at any time during study treatment, on two consecutive occasions >= 4 weeks apart, as determined by the investigator according to RECIST v1.1 or INRC. Per RECIST, CR was defined as disappearance of all target lesions. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD. Participants who had neuroblastoma were assessed by INRC. Per INRC, CR= <10 mm residual soft tissue at primary site and complete resolution of MIBG or FDG-PET uptake at primary site. PR= ≥ 30% decrease in longest diameter of primary site and MIBG or FDG-PET uptake at primary site stable, improved, or resolved. Soft tissue & bone metastases: CR= resolution of all disease sites; PR= ≥30% decrease in sum of non-primary target lesions, with no new lesions or ≥50% reduction in MIBG score or in number of FDG-PET-avid bone lesions; Bone marrow: CR= no tumor infiltration on reassessment.

SE population included all participants who received any amount of the study treatment, whether prematurely withdrawn from the study or not.

Posted

Number

95% Confidence Interval

percentage of participants

From screening (maximum 28 days) up to Cycle 5 (cycle length=28 days)

ID	Title	Description
OG000	Part 1a: Idasanutlin 2 mg/kg	Participants with solid tumors received idasanutlin 2 mg/kg QD on Days 1-5 of each 28-day cycle until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.

Secondary

Part 1b: ORR Irrespective of TP53 Status in Participants With Neuroblastoma From SE Population According to INRC

ORR was defined as the percentage of participants with CR or PR at any time during study treatment, on 2 consecutive occasions ≥ 4 weeks apart, as determined by the investigator per INRC. Primary tumor: CR= <10 mm residual soft tissue at primary site and complete resolution of MIBG or FDG-PET uptake at primary site. PR= ≥ 30% decrease in longest diameter of primary site and MIBG or FDG-PET uptake at primary site stable, improved, or resolved. Soft tissue & bone metastases: CR= resolution of all disease sites; PR= ≥30% decrease in sum of non-primary target lesions, with no new lesions or ≥50% reduction in MIBG score or in number of FDG-PET-avid bone lesions; Bone marrow: CR= no tumor infiltration on reassessment. Percentages have been rounded off to nearest decimal point.

SE population included all participants who received any amount of the study treatment, whether prematurely withdrawn from the study or not.

Posted

Number

95% Confidence Interval

percentage of participants

From screening (maximum 28 days) up to Cycle 6 (cycle length=28 days)

ID	Title	Description
OG000	Part 1b: Idasanutlin (2.8mg/kg) +Chemotherapy	Participants with neuroblastoma received idasanutlin 2.8 mg/kg orally in combination with cyclophosphamide 200 mg/m^2 and topotecan 0.6 mg/m^2 as an IV infusion QD on Days 1-5 of each 28-day cycle. Treatment was administered until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.
OG001

Secondary

Part 1a: Maximum Plasma Concentration (Cmax) of Idasanutlin as a Monotherapy

Pharmacokinetic (PK)-evaluable population included all participants who received at least one dose of study treatment and who have data from at least one post dose sample. One participant assigned to the 6.4 mg/kg dose level received a dose of 3.8 mg/kg due to the maximum absolute dose cap of 300 mg/day in protocol v3 and earlier. Hence this participant has been reported in a separate arm for PK analysis.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL(nanograms/millilitres)

Days 1 and 5 of Cycle 1 (cycle length = 28 days)

ID	Title	Description
OG000	Part 1a: Idasanutlin 2 mg/kg	Participants with solid tumors received idasanutlin 2 mg/kg QD on Days 1-5 of each 28-day cycle until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.
OG001	Part 1a: Idasanutlin 3 mg/kg	Participants with solid tumors received idasanutlin 3 mg/kg orally QD on Days 1-5 of each 28-day cycle until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.
OG002	Part 1a: Idasanutlin 3.8 mg/kg	Participants with solid tumors received idasanutlin 3.8 mg/kg orally QD on Days 1-5 of each 28-day cycle until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.

Secondary

Part 1b: Cmax of Idasanutlin in Combination With Chemotherapy or Venetoclax

PK-evaluable population included all participants who received at least one dose of study treatment and who have data from at least one post dose sample.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Days 1 and 5 of Cycle 1 (cycle length = 28 days)

ID	Title	Description
OG000	Part 1b: Idasanutlin (2.8mg/kg) +Chemotherapy	Participants with neuroblastoma received idasanutlin 2.8 mg/kg orally in combination with cyclophosphamide 200 mg/m^2 and topotecan 0.6 mg/m^2 as an IV infusion QD on Days 1-5 of each 28-day cycle. Treatment was administered until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.
OG001	Part 1b: Idasanutlin (3.6mg/kg) +Chemotherapy	Participants with neuroblastoma received idasanutlin 3.6 mg/kg orally in combination with cyclophosphamide 250 mg/m^2 and topotecan 0.75 mg/m^2 as an IV infusion QD on Days 1-5 of each 28-day cycle. Treatment was administered until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.
OG002	Part 1b: Idasanutlin (3.6mg/kg) + Venetoclax	Participants with neuroblastoma (first 3) received idasanutlin, 3.6 mg/kg orally QD on Days 1-5, in combination with venetoclax 400 mg adult dose equivalent (adjusted by body weight) on Days 1-28 of each 28-day cycle. After the first three participants were treated, the schedule was modified as idasanutlin, 3.6 mg/kg orally QD on Days 1-5 and venetoclax 400 mg (adult dose equivalent) on Days 1-14 of a each 28-day cycle for the next 3 participants enrolled in this arm. Treatment was administered until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.

Secondary

Part 1a: Cmax of Idasanutilin Metabolite M4 Following Idasanutilin as a Monotherapy

PK-evaluable population included all participants who received at least one dose of study treatment and who have data from at least one post dose sample. One participant assigned to the 6.4 mg/kg dose level received a dose of 3.8 mg/kg due to the maximum absolute dose cap of 300 mg/day in protocol v3 and earlier. Hence this participant has been reported in a separate arm for PK analysis.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Days 1 and 5 of Cycle 1 (cycle length = 28 days)

ID	Title	Description
OG000	Part 1a: Idasanutlin 2 mg/kg	Participants with solid tumors received idasanutlin 2 mg/kg QD on Days 1-5 of each 28-day cycle until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.
OG001	Part 1a: Idasanutlin 3 mg/kg	Participants with solid tumors received idasanutlin 3 mg/kg orally QD on Days 1-5 of each 28-day cycle until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.
OG002	Part 1a: Idasanutlin 3.8 mg/kg	Participants with solid tumors received idasanutlin 3.8 mg/kg orally QD on Days 1-5 of each 28-day cycle until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.

Secondary

Part 1b: Cmax of Idasanutlin Metabolite M4 (Idasanutilin in Combination With Chemotherapy or Venetoclax)

PK-evaluable population included all participants who received at least one dose of study treatment and who have data from at least one post dose sample.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Days 1 and 5 of Cycle 1 (cycle length = 28 days)

ID	Title	Description
OG000	Part 1b: Idasanutlin (2.8mg/kg) +Chemotherapy	Participants with neuroblastoma received idasanutlin 2.8 mg/kg orally in combination with cyclophosphamide 200 mg/m^2 and topotecan 0.6 mg/m^2 as an IV infusion QD on Days 1-5 of each 28-day cycle. Treatment was administered until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.
OG001	Part 1b: Idasanutlin (3.6mg/kg) +Chemotherapy	Participants with neuroblastoma received idasanutlin 3.6 mg/kg orally in combination with cyclophosphamide 250 mg/m^2 and topotecan 0.75 mg/m^2 as an IV infusion QD on Days 1-5 of each 28-day cycle. Treatment was administered until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.
OG002	Part 1b: Idasanutlin (3.6mg/kg) + Venetoclax	Participants with neuroblastoma (first 3) received idasanutlin, 3.6 mg/kg orally QD on Days 1-5, in combination with venetoclax 400 mg adult dose equivalent (adjusted by body weight) on Days 1-28 of each 28-day cycle. After the first three participants were treated, the schedule was modified as idasanutlin, 3.6 mg/kg orally QD on Days 1-5 and venetoclax 400 mg (adult dose equivalent) on Days 1-14 of a each 28-day cycle for the next 3 participants enrolled in this arm. Treatment was administered until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.

Secondary

Part 1b: Plasma Concentration of Venetoclax in Combination With Idasanutlin

PK-evaluable population included all participants who received at least one dose of study treatment and who have data from at least one post dose sample. Number analyzed is the number of participants with data available for analyses at the specified timepoints.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Cycle 1: Predose on Days 2 and 5, 4 and 6 hours post dose on Days 1 and 5 (1 cycle = 28 days)

ID	Title	Description
OG000	Part 1b: Idasanutlin (3.6mg/kg) + Venetoclax	Participants with neuroblastoma (first 3) received idasanutlin, 3.6 mg/kg orally QD on Days 1-5, in combination with venetoclax 400 mg adult dose equivalent (adjusted by body weight) on Days 1-28 of each 28-day cycle. After the first three participants were treated, the schedule was modified as idasanutlin, 3.6 mg/kg orally QD on Days 1-5 and venetoclax 400 mg (adult dose equivalent) on Days 1-14 of a each 28-day cycle for the next 3 participants enrolled in this arm. Treatment was administered until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.

Units	Counts
Participants	OG000

Secondary

Parts 1, 2 and 3: Number of Participants With Leukemia Receiving Transplant After Study Treatment

The study was terminated before initiation of Parts 2 and 3 as per sponsor's decision. No participants with leukemia were enrolled in Part 1. Hence no data were collected, and this outcome measure was not assessed or analyzed.

Posted

Up to approximately 29 months

ID	Title	Description
OG000	Part 1 (Leukemia)	Participants with AML and ALL were planned to be enrolled in various cohorts in Part 1. Participants with AML and ALL were to receive idasanutlin in combination venetoclax 400 mg. Participants with AML were to receive idasanutlin plus fludarabine 30 mg/m^2 and high dose cytarabine 2000 mg/m^2 (FLA) on Days 1-5 of each 28-day cycle.
OG001	Part 2 (Leukemia)	Participants with AML or ALL were planned to be enrolled in various cohorts in Part 2. Participants with AML were to receive idasanutlin plus fludarabine 30 mg/m^2 and high dose cytarabine 2000 mg/m^2 (FLA) on Days 1-5 of each 28-day cycle. Participants with ALL were to receive idasanutlin plus venetoclax 600 mg on Days 1-5 of each 28-day cycle.
OG002	Part 3: Expansion (Leukemia)	Potential expansion of idasanutlin combination cohorts for participants with TP35 WT AML or ALL from Part 1b and 2 meeting the pre-defined efficacy criteria were planned to be initiated in Part 3.

Secondary

Parts 1, 2 and 3: Duration of Objective Response in Participants With Leukemia

DOR, defined as the time from the first tumor assessment that supports the participant's objective response (CR, CRp, CRi) to the time of relapse, or death from any cause, whichever occurs first. CR=Bone marrow blasts <5% (AML) and no evidence of circulating blasts, must be <1% (ALL); absence of blasts with Auer rods (AML); absence of extramedullary disease; absolute neutrophil count (ANC) >1.0*10^9/L [1000µL]; platelet count > 100*10^9/L (100,000/µL); independence of transfusions for a minimum of 1 week (AML and ALL). CRi= All CR criteria except for ANC <1.0*10^9/L[1000/µL] or insufficient recovery of platelet count <100* 10^9/L [100,000/µL] (AML and ALL). CRp=All CR criteria except for ANC >1.0*10^9/L[1000/µL]) or but with insufficient recovery of platelet (<100* 10^9/L [100,000/µL]) (ALL). Relapse=participants who achieved a CR/CRp/CRi & subsequently developed: Bone marrow blasts ≥5%; reappearance of blasts in the blood ≥1%; or development of extra-medullary disease.

Posted

Up to approximately 29 months

ID	Title	Description
OG000	Part 1 (Leukemia)	Participants with AML or ALL were planned to be enrolled in various cohorts in Part 1. Participants with AML or ALL were to receive idasanutlin in combination venetoclax 400 mg. Participants with AML were to receive idasanutlin plus fludarabine 30 mg/m^2 and high dose cytarabine 2000 mg/m^2 (FLA) on Days 1-5 of each 28-day cycle.

Secondary

Parts 1, 2 and 3: Event-Free Survival (EFS) in Participants With Leukemia

EFS=time from initiation of study drug to first documented occurrence of M3 marrow after Cycle 1, failure to achieve CR/CRp/CRi after Cycle 2, disease progression, relapse after achieving CR/CRp/CRi, or death from any cause, whichever occurs first. CR=Bone marrow blasts <5% (AML) & no evidence of circulating blasts, must be <1% (ALL); absence of blasts with Auer rods (AML); absence of extramedullary disease; ANC >1.0*10^9/L [1000µL]; platelet count > 100*10^9/L (100,000/µL); no transfusions for a minimum of 1 week (AML & ALL). CRi= All CR criteria except for ANC <1.0*10^9/L[1000/µL] or insufficient recovery of platelet count <100* 10^9/L [100,000/µL] (AML & ALL). CRp=All CR criteria except for ANC >1.0*10^9/L[1000/µL]) or but with insufficient recovery of platelet (<100* 10^9/L [100,000/µL]) (ALL). Relapse=participants who achieved a CR/CRp/CRi & subsequently developed: Bone marrow blasts ≥5%; reappearance of blasts in blood ≥1%; or development of extra-medullary disease.

Posted

Up to approximately 29 months

ID	Title	Description
OG000	Part 1 (Leukemia)	Participants with AML or ALL were planned to be enrolled in various cohorts in Part 1. Participants with AML or ALL were to receive idasanutlin in combination venetoclax 400 mg. Participants with AML were to receive idasanutlin plus fludarabine 30 mg/m^2 and high dose cytarabine 2000 mg/m^2 (FLA) on Days 1-5 of each 28-day cycle.

Secondary

Parts 1, 2 and 3: OS in Participants With Leukemia

OS was defined as the time from initiation of study drug to death from any cause.

The study was terminated before initiation of Part 2 and 3 as per sponsor's decision. No participants with leukemia were enrolled in Part 1. Hence no data were collected, and this outcome measure was not assessed or analyzed.

Posted

Up to approximately 29 months

ID	Title	Description
OG000	Part 1 (Leukemia)	Participants with AML or ALL were planned to be enrolled in various cohorts in Part 1. Participants with AML or ALL were to receive idasanutlin in combination venetoclax 400 mg. Participants with AML were to receive idasanutlin plus fludarabine 30 mg/m^2 and high dose cytarabine 2000 mg/m^2 (FLA) on Days 1-5 of each 28-day cycle.
OG001	Part 2 (Leukemia)	Participants with AML or ALL were planned to be enrolled in various cohorts in Part 2. Participants with AML were to receive idasanutlin plus fludarabine 30 mg/m^2 and high dose cytarabine 2000 mg/m^2 (FLA) on Days 1-5 of each 28-day cycle. Participants with ALL were to receive idasanutlin plus venetoclax 600 mg on Days 1-5 of each 28-day cycle.
OG002	Part 3: Expansion (Leukemia)	Potential expansion of idasanutlin combination cohorts for participants with TP35 WT AML or ALL from Part 1b and 2 meeting the pre-defined efficacy criteria were planned to be initiated in Part 3.

Secondary

Parts 1, 2 and 3: CRR of Efficacy-evaluable Population Irrespective of TP53 Status in Participants With Leukemia

CRR was defined as the percentage of participants with CR, CRi, or CRp within 2 cycles of study treatment. CR=Bone marrow blasts <5% (AML) and no evidence of circulating blasts, must be <1% (ALL); absence of blasts with Auer rods (AML); absence of extramedullary disease; absolute neutrophil count (ANC) >1.0*10^9/L [1000/µL]; platelet count > 100*10^9/L (100,000/µL); independence of transfusions for a minimum of 1 week (AML and ALL). CRi= All CR criteria except for ANC <1.0*10^9/L[1000/µL] or insufficient recovery of platelet count <100* 10^9/L [100,000/µL] (AML and ALL). CRp=All CR criteria except for ANC >1.0*10^9/L[1000/µL]) or but with insufficient recovery of platelet (<100* 10^9/L [100,000/µL]) (ALL).

Posted

Up to approximately 29 months

ID	Title	Description
OG000	Part 1 (Leukemia)	Participants with AML or ALL were planned to be enrolled in various cohorts in Part 1. Participants with AML or ALL were to receive idasanutlin in combination venetoclax 400 mg. Participants with AML were to receive idasanutlin plus fludarabine 30 mg/m^2 and high dose cytarabine 2000 mg/m^2 (FLA) on Days 1-5 of each 28-day cycle.
OG001	Part 2 (Leukemia)

Secondary

Parts 1, 2 and 3: MRD - Negative Rate in Participants With ALL

MRD - negative rate was defined as defined as the percentage of participants with AML who are MRD negative within 2 cycles of study treatment.

Posted

Up to approximately 29 months

ID	Title	Description
OG000	Part 1 (ALL)	Participants with ALL were planned to be enrolled in various cohorts in Part 1 and receive idasanutlin in combination venetoclax 400 mg.
OG001	Part 2 (ALL)	Participants with ALL were planned to be enrolled in Part 2 and receive idasanutlin plus venetoclax 600 mg on Days 1-5 of each 28-day cycle.
OG002	Part 3: Expansion (ALL)	Potential expansion of idasanutlin combination cohorts for participants with TP35 WT ALL from Part 1b and 2 meeting the pre-defined efficacy criteria were planned to be initiated in Part 3.

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	Part 1a: Idasanutlin 2 mg/kg	Participants with solid tumors received idasanutlin 2 mg/kg QD on Days 1-5 of each 28-day cycle until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.	8	8	6	8	8	8
EG001	Part 1a: Idasanutlin 3 mg/kg	Participants with solid tumors received idasanutlin 3 mg/kg orally QD on Days 1-5 of each 28-day cycle until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.	3	3	3	3	3	3
EG002	Part 1a: Idasanutlin 4.5 mg/kg	Participants with solid tumors received idasanutlin 4.5 mg/kg orally QD on Days 1-5 of each 28-day cycle until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.	6	6	4	6	6	6
EG003	Part 1a: Idasanutlin 6.4 mg/kg	Participants with solid tumors received idasanutlin 6.4 mg/kg orally QD on Days 1-5 of each 28-day cycle until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.	2	3	2	3	3	3
EG004	Part 1a: Idasanutlin 8 mg/kg	Participants with solid tumors received idasanutlin 8 mg/kg orally QD on Days 1-5 of each 28-day cycle until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.	5	6	6	6	6	6
EG005	Part 1b: Idasanutlin (2.8mg/kg) +Chemotherapy	Participants with neuroblastoma received idasanutlin 2.8 mg/kg orally in combination with cyclophosphamide 200 mg/m^2 and topotecan 0.6 mg/m^2 as an IV infusion QD on Days 1-5 of each 28-day cycle. Treatment was administered until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.	0	3	2	3	3	3
EG006	Part 1b: Idasanutlin (3.6 mg/kg) +Chemotherapy	Participants with neuroblastoma received idasanutlin, 3.6 mg/kg orally, in combination with cyclophosphamide 250 mg/m^2 and topotecan 0.75 mg/m^2 as an IV infusion QD on Days 1-5 of each 28-day cycle. Treatment was administered until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.	2	3	3	3	3	3
EG007	Part 1b: Idasanutlin (3.6mg/kg) + Venetoclax	Participants with neuroblastoma (first 3) received idasanutlin, 3.6 mg/kg orally QD on Days 1-5, in combination with venetoclax 400 mg adult dose equivalent (adjusted by body weight) on Days 1-28 of each 28-day cycle. After the first three participants were treated, the schedule was modified as idasanutlin, 3.6 mg/kg orally QD on Days 1-5 and venetoclax 400 mg (adult dose equivalent) on Days 1-14 of a each 28-day cycle for the next 3 participants enrolled in this arm. Treatment was administered until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.	3	6	4	6	6	6

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anemia	Blood and lymphatic system disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG0031 events1 affected3 at risk EG0040 events0 affected6 at risk EG0050 events0 affected3 at risk EG0060 events0 affected3 at risk EG0070 events0 affected6 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA version 25.0	Systematic Assessment	EG0006 events3 affected8 at risk EG0013 events2 affected3 at risk EG0023 events2 affected6 at risk EG003
Hematotoxicity	Blood and lymphatic system disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Leukopenia	Blood and lymphatic system disorders	MedDRA version 25.0	Systematic Assessment	EG0004 events2 affected8 at risk EG0011 events1 affected3 at risk EG0020 events0 affected6 at risk EG003
Lymphopenia	Blood and lymphatic system disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA version 25.0	Systematic Assessment	EG0007 events3 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Pancytopenia	Blood and lymphatic system disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0021 events1 affected6 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA version 25.0	Systematic Assessment	EG0007 events4 affected8 at risk EG0011 events1 affected3 at risk EG0020 events0 affected6 at risk EG003
Sinus tachycardia	Cardiac disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Hypoacusis	Ear and labyrinth disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected3 at risk EG0021 events1 affected6 at risk EG003
Pyrexia	General disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Appendicitis	Infections and infestations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected3 at risk EG0020 events0 affected6 at risk EG003
Bacteraemia	Infections and infestations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Cellulitis	Infections and infestations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0021 events1 affected6 at risk EG003
Central nervous system infection	Infections and infestations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Sepsis	Infections and infestations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0021 events1 affected6 at risk EG003
Sinusitis	Infections and infestations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected3 at risk EG0020 events0 affected6 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Eschar	Injury, poisoning and procedural complications	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0021 events1 affected6 at risk EG003
Femoral neck fracture	Injury, poisoning and procedural complications	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0021 events1 affected6 at risk EG003
Lymphocyte count decreased	Investigations	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Platelet count decreased	Investigations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected3 at risk EG0020 events0 affected6 at risk EG003
Weight decreased	Investigations	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected3 at risk EG0020 events0 affected6 at risk EG003
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Hemorrhage intracranial	Nervous system disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Headache	Nervous system disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Partial seizures	Nervous system disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Seizure	Nervous system disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0021 events1 affected6 at risk EG003
Dyspnea	Respiratory, thoracic and mediastinal disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Hemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anemia	Blood and lymphatic system disorders	MedDRA version 25.0	Systematic Assessment	EG0005 events4 affected8 at risk EG0012 events2 affected3 at risk EG0024 events3 affected6 at risk EG0031 events1 affected3 at risk EG0046 events6 affected6 at risk EG0054 events3 affected3 at risk EG0069 events3 affected3 at risk EG0071 events1 affected6 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0021 events1 affected6 at risk EG003
Leukopenia	Blood and lymphatic system disorders	MedDRA version 25.0	Systematic Assessment	EG0003 events3 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Lymphopenia	Blood and lymphatic system disorders	MedDRA version 25.0	Systematic Assessment	EG0002 events2 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA version 25.0	Systematic Assessment	EG0002 events2 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA version 25.0	Systematic Assessment	EG0002 events2 affected8 at risk EG0011 events1 affected3 at risk EG0022 events2 affected6 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA version 25.0	Systematic Assessment	EG0005 events3 affected8 at risk EG0012 events1 affected3 at risk EG0020 events0 affected6 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0014 events2 affected3 at risk EG0022 events2 affected6 at risk EG003
Diarrhea	Gastrointestinal disorders	MedDRA version 25.0	Systematic Assessment	EG0004 events3 affected8 at risk EG0013 events1 affected3 at risk EG0027 events5 affected6 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0021 events1 affected6 at risk EG003
Lip swelling	Gastrointestinal disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA version 25.0	Systematic Assessment	EG0004 events3 affected8 at risk EG0016 events2 affected3 at risk EG0026 events4 affected6 at risk EG003
Oral pain	Gastrointestinal disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0013 events2 affected3 at risk EG0020 events0 affected6 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected3 at risk EG0020 events0 affected6 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA version 25.0	Systematic Assessment	EG0007 events4 affected8 at risk EG0018 events2 affected3 at risk EG0029 events4 affected6 at risk EG003
Asthenia	General disorders	MedDRA version 25.0	Systematic Assessment	EG0003 events2 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Fatigue	General disorders	MedDRA version 25.0	Systematic Assessment	EG0005 events3 affected8 at risk EG0011 events1 affected3 at risk EG0023 events2 affected6 at risk EG003
Mucosal inflammation	General disorders	MedDRA version 25.0	Systematic Assessment	EG0002 events2 affected8 at risk EG0011 events1 affected3 at risk EG0020 events0 affected6 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0015 events1 affected3 at risk EG0021 events1 affected6 at risk EG003
Pain	General disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0011 events1 affected3 at risk EG0024 events3 affected6 at risk EG003
Pyrexia	General disorders	MedDRA version 25.0	Systematic Assessment	EG0003 events3 affected8 at risk EG0013 events3 affected3 at risk EG0023 events2 affected6 at risk EG003
Bacteraemia	Infections and infestations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Mucosal infection	Infections and infestations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Oral candidiasis	Infections and infestations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Skin infection	Infections and infestations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0021 events1 affected6 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0022 events1 affected6 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA version 25.0	Systematic Assessment	EG0002 events2 affected8 at risk EG0010 events0 affected3 at risk EG0021 events1 affected6 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA version 25.0	Systematic Assessment	EG0004 events4 affected8 at risk EG0010 events0 affected3 at risk EG0021 events1 affected6 at risk EG003
Blood alkaline phosphatase increased	Investigations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Blood bicarbonate increased	Investigations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Blood bilirubin increased	Investigations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Blood chloride decreased	Investigations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Blood creatinine increased	Investigations	MedDRA version 25.0	Systematic Assessment	EG0002 events1 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Blood uric acid increased	Investigations	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Gamma-glutamyltransferase increased	Investigations	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Lymphocyte count decreased	Investigations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Neutrophil count decreased	Investigations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Platelet count decreased	Investigations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Weight decreased	Investigations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
White blood cell count decreased	Investigations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0012 events1 affected3 at risk EG0023 events2 affected6 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected3 at risk EG0021 events1 affected6 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA version 25.0	Systematic Assessment	EG0002 events1 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA version 25.0	Systematic Assessment	EG0002 events1 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0021 events1 affected6 at risk EG003
Groin pain	Musculoskeletal and connective tissue disorders	MedDRA version 25.0	Systematic Assessment	EG0002 events2 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA version 25.0	Systematic Assessment	EG0004 events2 affected8 at risk EG0010 events0 affected3 at risk EG0022 events2 affected6 at risk EG003
Headache	Nervous system disorders	MedDRA version 25.0	Systematic Assessment	EG0005 events2 affected8 at risk EG0010 events0 affected3 at risk EG0022 events2 affected6 at risk EG003
Lethargy	Nervous system disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0022 events2 affected6 at risk EG003
Seizure	Nervous system disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Tremor	Nervous system disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0021 events1 affected6 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0013 events1 affected3 at risk EG0020 events0 affected6 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected3 at risk EG0021 events1 affected6 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0021 events1 affected6 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Skin exfoliation	Skin and subcutaneous tissue disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Skin hyperpigmentation	Skin and subcutaneous tissue disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0021 events1 affected6 at risk EG003
Ear pain	Ear and labyrinth disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected3 at risk EG0020 events0 affected6 at risk EG003
Eye pain	Eye disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0021 events1 affected6 at risk EG003
Periorbital edema	Eye disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Anal fissure	Gastrointestinal disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected3 at risk EG0020 events0 affected6 at risk EG003
Hematochezia	Gastrointestinal disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Mouth swelling	Gastrointestinal disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0021 events1 affected6 at risk EG003
Swelling	General disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Vascular device occlusion	General disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0021 events1 affected6 at risk EG003
COVID-19	Infections and infestations	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Device related infection	Infections and infestations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected3 at risk EG0020 events0 affected6 at risk EG003
Fungal skin infection	Infections and infestations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected3 at risk EG0020 events0 affected6 at risk EG003
Lower respiratory tract infection	Infections and infestations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0021 events1 affected6 at risk EG003
Lymphangitis	Infections and infestations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0021 events1 affected6 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0021 events1 affected6 at risk EG003
Parainfluenzae virus infection	Infections and infestations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0021 events1 affected6 at risk EG003
Paronychia	Infections and infestations	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Respiratory tract infection	Infections and infestations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0021 events1 affected6 at risk EG003
Accidental overdose	Injury, poisoning and procedural complications	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Pelvic fracture	Injury, poisoning and procedural complications	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected3 at risk EG0020 events0 affected6 at risk EG003
Blood lactate dehydrogenase increased	Investigations	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Blood phosphorus decreased	Investigations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
SARS-CoV-2 test positive	Investigations	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected3 at risk EG0020 events0 affected6 at risk EG003
Dizziness	Nervous system disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected3 at risk EG0020 events0 affected6 at risk EG003
Agitation	Psychiatric disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Anxiety	Psychiatric disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Confusional state	Psychiatric disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Insomnia	Psychiatric disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Irritability	Psychiatric disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0021 events1 affected6 at risk EG003
Dysuria	Renal and urinary disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Pollakiuria	Renal and urinary disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0023 events1 affected6 at risk EG003
Dyspnea	Respiratory, thoracic and mediastinal disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0012 events1 affected3 at risk EG0020 events0 affected6 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0021 events1 affected6 at risk EG003
Tachypnoea	Respiratory, thoracic and mediastinal disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0022 events1 affected6 at risk EG003
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0021 events1 affected6 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA version 25.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected3 at risk EG0020 events0 affected6 at risk EG003
Livedo reticularis	Skin and subcutaneous tissue disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0021 events1 affected6 at risk EG003
Pain of skin	Skin and subcutaneous tissue disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected3 at risk EG0021 events1 affected6 at risk EG003
Purpura	Skin and subcutaneous tissue disorders	MedDRA version 25.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0012 events1 affected3 at risk EG0020 events0 affected6 at risk EG003

First MCP Posted Date

ID	Term
D015470	Leukemia, Myeloid, Acute
D054198	Precursor Cell Lymphoblastic Leukemia-Lymphoma
D009447	Neuroblastoma

Ancestor Terms

ID	Term
D007951	Leukemia, Myeloid
D007938	Leukemia
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D007945	Leukemia, Lymphoid
D008232	Lymphoproliferative Disorders
D008206	Lymphatic Diseases
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases
D018241	Neuroectodermal Tumors, Primitive, Peripheral
D018242	Neuroectodermal Tumors, Primitive
D018302	Neoplasms, Neuroepithelial
D017599	Neuroectodermal Tumors
D009373	Neoplasms, Germ Cell and Embryonal
D009375	Neoplasms, Glandular and Epithelial
D009380	Neoplasms, Nerve Tissue

ID	Term
C586849	RG7388
C579720	venetoclax
D003520	Cyclophosphamide
D019772	Topotecan
C024352	fludarabine
D003561	Cytarabine

Ancestor Terms

ID	Term
D010752	Phosphoramide Mustards
D009588	Nitrogen Mustard Compounds
D009150	Mustard Compounds
D006846	Hydrocarbons, Halogenated
D006838	Hydrocarbons
D009930	Organic Chemicals
D063088	Phosphoramides
D009943	Organophosphorus Compounds
D002166	Camptothecin
D000470	Alkaloids
D006571	Heterocyclic Compounds
D003562	Cytidine
D011741	Pyrimidine Nucleosides
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring
D001087	Arabinonucleosides
D009705	Nucleosides
D009706	Nucleic Acids, Nucleotides, and Nucleosides

Participants with neuroblastoma received idasanutlin, 3.6 mg/kg orally, in combination with cyclophosphamide 250 mg/m^2 and topotecan 0.75 mg/m^2 as an IV infusion QD on Days 1-5 of each 28-day cycle. Treatment was administered until disease progression, death, unacceptable toxicity, or decision to discontinue, whichever occurred first.

EG0045 events3 affected6 at risk

EG0051 events1 affected3 at risk

EG0063 events2 affected3 at risk

EG0070 events0 affected6 at risk

EG0041 events1 affected6 at risk

EG0050 events0 affected3 at risk

EG0060 events0 affected3 at risk

EG0070 events0 affected6 at risk

EG0041 events1 affected6 at risk

EG0050 events0 affected3 at risk

EG0060 events0 affected3 at risk

EG0070 events0 affected6 at risk

EG0040 events0 affected6 at risk

EG0050 events0 affected3 at risk

EG0060 events0 affected3 at risk

EG0070 events0 affected6 at risk

EG0042 events2 affected6 at risk

EG0050 events0 affected3 at risk

EG0060 events0 affected3 at risk

EG0070 events0 affected6 at risk

EG0040 events0 affected6 at risk

EG0050 events0 affected3 at risk

EG0060 events0 affected3 at risk

EG0071 events1 affected6 at risk

EG0042 events2 affected6 at risk

EG0050 events0 affected3 at risk

EG0060 events0 affected3 at risk

EG0071 events1 affected6 at risk

EG0040 events0 affected6 at risk

EG0050 events0 affected3 at risk

EG0060 events0 affected3 at risk

EG0070 events0 affected6 at risk

EG0040 events0 affected6 at risk

EG0050 events0 affected3 at risk

EG0061 events1 affected3 at risk

EG0070 events0 affected6 at risk

EG0040 events0 affected6 at risk

EG0050 events0 affected3 at risk

EG0060 events0 affected3 at risk

EG0072 events1 affected6 at risk

EG0040 events0 affected6 at risk

EG0050 events0 affected3 at risk

EG0061 events1 affected3 at risk

EG0070 events0 affected6 at risk

EG0040 events0 affected6 at risk

EG0050 events0 affected3 at risk

EG0060 events0 affected3 at risk

EG0074 events2 affected6 at risk

EG0040 events0 affected6 at risk

EG0051 events1 affected3 at risk

EG0061 events1 affected3 at risk

EG0071 events1 affected6 at risk

EG0040 events0 affected6 at risk

EG0050 events0 affected3 at risk

EG0060 events0 affected3 at risk

EG0070 events0 affected6 at risk

EG0040 events0 affected6 at risk

EG0050 events0 affected3 at risk

EG0061 events1 affected3 at risk

EG0070 events0 affected6 at risk

EG0040 events0 affected6 at risk

EG0050 events0 affected3 at risk

EG0060 events0 affected3 at risk

EG0070 events0 affected6 at risk

EG0040 events0 affected6 at risk

EG0050 events0 affected3 at risk

EG0060 events0 affected3 at risk

EG0070 events0 affected6 at risk

EG0040 events0 affected6 at risk

EG0050 events0 affected3 at risk

EG0060 events0 affected3 at risk

EG0070 events0 affected6 at risk

EG0040 events0 affected6 at risk

EG0050 events0 affected3 at risk

EG0060 events0 affected3 at risk

EG0070 events0 affected6 at risk

EG0040 events0 affected6 at risk

EG0050 events0 affected3 at risk

EG0060 events0 affected3 at risk

EG0070 events0 affected6 at risk

EG0040 events0 affected6 at risk

EG0050 events0 affected3 at risk

EG0060 events0 affected3 at risk

EG0070 events0 affected6 at risk

EG0040 events0 affected6 at risk

EG0050 events0 affected3 at risk

EG0060 events0 affected3 at risk

EG0070 events0 affected6 at risk

EG0041 events1 affected6 at risk

EG0050 events0 affected3 at risk

EG0060 events0 affected3 at risk

EG0070 events0 affected6 at risk

EG0040 events0 affected6 at risk

EG0050 events0 affected3 at risk

EG0061 events1 affected3 at risk

EG0070 events0 affected6 at risk

EG0040 events0 affected6 at risk

EG0050 events0 affected3 at risk

EG0060 events0 affected3 at risk

EG0070 events0 affected6 at risk

EG0040 events0 affected6 at risk

EG0050 events0 affected3 at risk

EG0060 events0 affected3 at risk

EG0071 events1 affected6 at risk

EG0040 events0 affected6 at risk

EG0050 events0 affected3 at risk

EG0060 events0 affected3 at risk

EG0070 events0 affected6 at risk

EG0040 events0 affected6 at risk

EG0050 events0 affected3 at risk

EG0060 events0 affected3 at risk

EG0071 events1 affected6 at risk

EG0040 events0 affected6 at risk

EG0050 events0 affected3 at risk

EG0060 events0 affected3 at risk

EG0071 events1 affected6 at risk

EG0040 events0 affected6 at risk

EG0050 events0 affected3 at risk

EG0060 events0 affected3 at risk

EG0070 events0 affected6 at risk

EG0041 events1 affected6 at risk

EG0050 events0 affected3 at risk

EG0060 events0 affected3 at risk

EG0070 events0 affected6 at risk

EG0041 events1 affected6 at risk

EG0050 events0 affected3 at risk

EG0060 events0 affected3 at risk

EG0070 events0 affected6 at risk

EG0040 events0 affected6 at risk

EG0050 events0 affected3 at risk

EG0061 events1 affected3 at risk

EG0070 events0 affected6 at risk

EG0040 events0 affected6 at risk

EG0050 events0 affected3 at risk

EG0060 events0 affected3 at risk

EG0070 events0 affected6 at risk

EG0040 events0 affected6 at risk

EG0050 events0 affected3 at risk

EG0060 events0 affected3 at risk

EG0070 events0 affected6 at risk

EG0041 events1 affected6 at risk

EG0050 events0 affected3 at risk