A Safety and Antitumor Activity Trial of Immunoradiotherapy Combinations as a Treatment Option for Subjects With Metastatic Solid Tumors

• ClinicalTrials.gov Identifier: NCT05491317
• Recruitment Status: Recruiting
• First Posted: August 8, 2022
• Last Update Posted: February 6, 2024
• Sponsor: Genmab
• Collaborator: BioNTech SE
• Information provided by (Responsible Party): Genmab

Study Description

Brief Summary:

The main purpose is to assess the safety and clinical activity of GEN1042 in combination with radiotherapy or GEN1042 in combination with radiotherapy and pembrolizumab as a treatment option for participants with metastatic solid tumors.

Condition or disease	Intervention/treatment	Phase
Non-CNS Tumor	Biological: GEN1042; Drug: Pembrolizumab; Radiation: Radiotherapy	Phase 1; Phase 2

Detailed Description:

The study will be conducted in two parts: Part 1 (dose-finding) and Part 2 (randomization).

Part 1 will evaluate the safety of immunoradiotherapy combinations and establish the dose(s) to be evaluated in Part 2.

Part 2 will evaluate the anti-tumor activity of immunoradiotherapy combinations at the established dose(s) from Part 1.

Participants in both parts are treated with one of the following combinations:

• Radiotherapy + GEN1042
• Radiotherapy + GEN1042 + Pembrolizumab

While participants in Part 1 are assigned sequentially (GEN1042 without pembrolizumab is investigated first), participants in Part 2 are randomized 1:1 in the two treatment arms.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 88 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: Part 1 is sequential, Part 2 is parallel (randomized)
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1 Dose Finding and Phase 2, Randomized, Open-Label Trial to Evaluate the Safety and Clinical Activity of Immunoradiotherapy Combinations as a Treatment Option in Subjects With Metastatic Solid Tumors
• Actual Study Start Date: March 8, 2023
• Estimated Primary Completion Date: July 2026
• Estimated Study Completion Date: July 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: Radiotherapy + GEN1042	Biological: GEN1042; Intravenous; Radiation: Radiotherapy; Radiotherapy
Experimental: Radiotherapy + GEN1042 + Pembrolizumab	Biological: GEN1042; Intravenous; Drug: Pembrolizumab; Intravenous; Radiation: Radiotherapy; Radiotherapy

Outcome Measures

Primary Outcome Measures :

1. Part 1: Number of Participants with Dose Limiting Toxicities (DLTs) [ Time Frame: During the first cycle (Cycle length = 21 days) ]
   Toxicities will be graded for severity according to the National Cancer Institute-Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v5.0).
2. Part 2: Number of Participants with Abscopal Response in Non-irradiated Target Lesions [ Time Frame: Up to 12 months after the last radiation treatment ]
   Assessed by investigator.

Secondary Outcome Measures :

1. Parts 1 and 2: Objective Response Rate (ORR) [ Time Frame: Up to 3 years ]
   ORR is defined as percentage of participants with a confirmed best overall response (BOR) of complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST) v1.1 as assessed by investigator.
2. Parts 1 and 2: Duration of Response (DOR) [ Time Frame: Up to 3 years ]
   DOR is defined as the time from the onset date of response to the date of the first documented progression or death due to any cause based on RECIST v1.1 as assessed by investigator.
3. Parts 1 and 2: Disease Control Rate (DCR) [ Time Frame: Up to 3 years ]
   The disease control rate (DCR) is defined as the percentage of participants with BOR of CR, PR, and stable disease (SD) according to RECIST v1.1.
4. Parts 1 and 2: Progression Free Survival (PFS) [ Time Frame: Up to 3 years ]
   PFS is defined as the time from the date of randomization (or date of first administration of GEN1042 ± pembrolizumab treatment for participants in Part 1) to the date of the first documented progression or death due to any cause based on RECIST v1.1 as assessed by investigator.
5. Parts 1 and 2: Overall Survival (OS) [ Time Frame: Up to 3 years ]
   OS is defined as the time from date of randomization (or date of first administration of GEN1042 ± pembrolizumab treatment for participants in Part 1) to date of death due to any cause.
6. Part 1: Number of Participants With Abscopal Response in Non-irradiated Target Lesions [ Time Frame: Up to 12 months after the last radiation treatment ]
   Assessed by investigator.
7. Parts 1 and 2: Number of Participants with Adverse Events (AEs) [ Time Frame: From screening until the end of the safety follow-up period (30 days or 90 days after last dose) ]
8. Parts 1 and 2: Area Under the Concentration-time Curve (AUC) of GEN1042 [ Time Frame: Predose and postdose at multiple timepoints up to 30 days after last dose ]
9. Parts 1 and 2: Maximum (Peak) Plasma Concentration (Cmax) [ Time Frame: Predose and postdose at multiple timepoints up to 30 days after last dose ]
10. Parts 1 and 2: Elimination Half-life (T1/2) of GEN1042 [ Time Frame: Predose and postdose at multiple timepoints up to 30 days after last dose ]
11. Parts 1 and 2: Number of Participants with Anti-drug Antibodies (ADAs) [ Time Frame: Predose at multiple timepoints up to 30 days after last dose ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Key Inclusion Criteria:

• Participants with histologically confirmed non-central nervous system (CNS) solid tumor that is metastatic and for whom there is no available standard therapy.
• At least 18 years of age.
• Signed informed consent prior to any screening procedures.
• Measurable disease according to RECIST v1.1.
• Life expectancy of >3 months.
• Qualify for palliative radiotherapy as an available option for disease management.
• Eastern Cooperative Oncology Group (ECOG) 0-1.
• Normal or adequate liver, renal, cardiac and bone marrow function.

Key Exclusion Criteria:

• Prior malignancy except for non-melanoma skin cancers and in situ cancers.
• Condition contraindicating radiotherapy.
• Rapidly progressing disease.
• Active, known or suspected autoimmune disease.
• History of non-infectious pneumonitis that required steroids or currently has pneumonitis.
• Contraindications to the use of pembrolizumab.
• Condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of first treatment.
• Received an allogeneic tissue/solid organ transplant.
• Active infection requiring systemic therapy.

Note: Other protocol defined inclusion and exclusion criteria may apply.

Contacts and Locations

Contacts

Contact: Genmab Trial Information; +4570202728; clinicaltrials@genmab.com

Locations

France

Institut Bergonie; Recruiting

Bordeaux, France, 33076

Oscar Lambret Center; Recruiting

Lille, France, 59000

Centre Leon Berard; Recruiting

Lyon, France, 69008

Institut Gustave Roussy; Recruiting

Villejuif, France, 94805

Sponsors and Collaborators

Genmab

BioNTech SE

Investigators

• Study Director: Study Official; Genmab

More Information

• Responsible Party: Genmab
• ClinicalTrials.gov Identifier: NCT05491317
• Other Study ID Numbers: GCT1042-02; 2022-000509-29 ( EudraCT Number )
• First Posted: August 8, 2022
• Last Update Posted: February 6, 2024
• Last Verified: February 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Additional relevant MeSH terms:

Pembrolizumab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immune Checkpoint Inhibitors; Molecular Mechanisms of Pharmacological Action