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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Malignant Solid Tumor
• Intervention / Treatment: Drug: Carboplatin; Drug: Cisplatin; Drug: Pembrolizumab; Biological: GEN1042; Drug: 5-Fluorouracil

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Genmab Trial Information; Phone Number: +4570202728; Email: clinicaltrials@genmab.com

Study Locations

• Japan
  • Kashiwa, Japan
    • Recruiting
    • Genmab Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Must have measurable disease according to RECIST v1.1.
2. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.
3. Acceptable organ and bone marrow function.
4. Participant must have a life expectancy of at least 3 months.

Key Exclusion Criteria:

1. Has clinically significant toxicities from previous anticancer therapies.
2. Has rapidly progressing disease.
3. Has a history of noninfectious pneumonitis/interstitial lung disease.
4. Has a history of liver disease.
5. 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.
6. Has any history of intracerebral arteriovenous malformation, cerebral aneurysm, or progressive brain metastases or stroke.
7. Has had major surgery within 4 weeks before Screening.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Genmab
• Collaborators: BioNTech SE
• Investigators: Study Director: Study Official, Genmab

Study record dates

Study Major Dates

• Study Start (Actual): November 24, 2023
• Primary Completion (Estimated): May 29, 2026
• Study Completion (Estimated): October 7, 2027

Study Registration Dates

• First Submitted: September 21, 2023
• First Submitted That Met QC Criteria: September 21, 2023
• First Posted (Actual): September 28, 2023

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Carboplatin; Fluorouracil; Pembrolizumab
• Other Study ID Numbers: GCT1042-03; jRCT2031230438 (Registry Identifier: Japan Registry of Clinical Trials (JRCT))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes