A Safety Trial of GEN1042 in Japanese Subjects With Malignant Solid Tumors

Study Overview
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Brief Summary
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This study evaluating GEN1042 will include multiple parts. In this study, GEN1042 alone (phase 1a) or GEN1042 in combination with other anticancer drug(s) (phase 1b) will be evaluated in Japanese participants. The main purpose is to assess the safety and tolerability of GEN1042 monotherapy or GEN1042 in combination in Japanese study participants with cancer.

Detailed Description
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This is an open-label, trial to evaluate the safety and tolerability, pharmacokinetics (PK), pharmacodynamics, and antitumor activity of GEN1042 in Japanese participants with malignant solid tumors. The trial consists of 2 parts: a GEN1042 Monotherapy Dose Escalation Part (phase 1a); and a Combination Therapy Part (phase 1b). The purpose of Dose Escalation Part (phase 1a) is to evaluate GEN1042 as monotherapy. The Combination Therapy Part (phase 1b) will evaluate GEN1042 in combination with pembrolizumab (pembro) or pembro along with the standard of care (SOC) chemotherapy.

Official Title
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A Phase 1 Study to Evaluate the Safety and Tolerability, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of GEN1042 Monotherapy and in Combination With Pembrolizumab ± Chemotherapy in Japanese Subjects With Malignant Solid Tumors

Conditions
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Malignant Solid Tumor

Intervention / Treatment
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* Biological: GEN1042
* Drug: Pembrolizumab
* Drug: Cisplatin
* Drug: Carboplatin
* Drug: 5-Fluorouracil


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Must have measurable disease according to RECIST v1.1. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1. Acceptable organ and bone marrow function. Participant must have a life expectancy of at least 3 months. Key Exclusion Criteria: Has clinically significant toxicities from previous anticancer therapies. Has rapidly progressing disease. Has a history of noninfectious pneumonitis/interstitial lung disease. Has a history of liver disease. Has had an allogeneic tissue/solid organ transplant or autologous or allogeneic bone marrow transplant, or stem cell rescue within 3 months prior to the first dose of GEN1042. Has any history of intracerebral arteriovenous malformation, cerebral aneurysm, or progressive brain metastases or stroke. Has had major surgery within 4 weeks before Screening. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Monotherapy (Non-central Nervous System (non-CNS) Malignant Solid Tumors): GEN1042<br> | Biological: GEN1042<br>* Intravenous<br>* Other names: GEN1042 (DuoBody®-CD40x4-1BB);|
| Experimental: Combination Therapy Cohort1[Head & Neck Squamous Cell Carcinoma (HNSCC)]:GEN1042+Pembro+Chemotherapy<br> | Biological: GEN1042<br>* Intravenous<br>* Other names: GEN1042 (DuoBody®-CD40x4-1BB);Drug: Pembrolizumab<br>* Intravenous<br>Drug: Cisplatin<br>* Intravenous<br>Drug: Carboplatin<br>* Intravenous<br>Drug: 5-Fluorouracil<br>* Intravenous<br>|
| Experimental: Combination Therapy Cohort 2 [HNSCC and Non-small-cell Lung Cancer (NSCLC)]: GEN1042 + Pembro<br> | Biological: GEN1042<br>* Intravenous<br>* Other names: GEN1042 (DuoBody®-CD40x4-1BB);Drug: Pembrolizumab<br>* Intravenous<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Dose Limiting Toxicities (DLTs) | Toxicities will be graded for severity according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE), version (v) 5.0. | During the first cycle (Cycle length = 21 days) | 
| Percentage of Participants with Adverse Events (AEs) | An AE is any untoward medical occurrence in a participant or clinical trial participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. | From first dose until the end of the safety follow-up period (90 days after last dose) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum (Peak) Plasma Concentration (Cmax) of GEN1042 |  | Predose and postdose at multiple timepoints up to 90 days after last dose | 
| Area Under the Concentration-time Curve (AUC) From Time Zero to Last Quantifiable Sample (AUClast) of GEN1042 |  | Predose and postdose at multiple timepoints up to 90 days after last dose | 
| Time to Reach Cmax (Tmax) of GEN1042 |  | Predose and postdose at multiple timepoints up to 90 days after last dose | 
| Number of Participants with Anti-drug Antibodies (ADA) to GEN1042 | Serum samples will be screened for ADAs binding to GEN1042 and the titer of confirmed positive samples will be reported. | up to 90 days after the last dose | 
| Objective Response Rate (ORR) | ORR is defined as percentage of participants with a best overall response (BOR) (Complete Response (CR) or Partial Response (PR)) confirmed by a subsequent BOR of CR or PR at least 4 weeks later per response evaluation criteria in solid tumors (RECIST) v1.1 based on investigator assessment. | Up to 3 years | 
| Duration of Response (DOR) | DOR only applies to participants whose confirmed BOR is CR or PR and is defined as time from the first documentation of objective tumor response (CR or PR) to the date of first disease progression (PD) or death per RECIST criteria v1.1 based on investigator assessment. | Up to 3 years | 
| Disease Control Rate (DCR) | The DCR is defined as the percentage of participants with BOR of confirmed CR, confirmed PR, or Stable Disease (SD) per RECIST criteria v1.1 based on investigator assessment. | Up to 3 years | 
| Progression Free Survival (PFS) | PFS is defined as the time from Day 1 in Cycle 1 to the first documented progression or death due to any cause per RECIST criteria v1.1 based on investigator assessment. | Up to 3 years |