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

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

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.

Study Overview

• Status: Terminated
• Conditions: Non-CNS Tumor
• Intervention / Treatment: Radiation: Radiotherapy; Drug: Pembrolizumab; Biological: GEN1042

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 Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• France
  • Lyon, France, 69008
    • Centre Leon Berard
  • Villejuif, France, 94805
    • Institut Gustave Roussy

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Radiotherapy + GEN1042	Radiation: Radiotherapy; Radiotherapy; Biological: GEN1042; Intravenous
Experimental: Radiotherapy + GEN1042 + Pembrolizumab	Radiation: Radiotherapy; Radiotherapy; Drug: Pembrolizumab; Intravenous; Biological: GEN1042; Intravenous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Dose Limiting Toxicities (DLTs)	A DLT was defined as any grade 5 toxicity, treatment-related toxicity that caused the participant to discontinue treatment during Cycle 1, febrile neutropenia grade 3 or grade 4, grade 3 thrombocytopenia associated with clinically significant bleeding, grade 4 thrombocytopenia of any duration, grade 4 anemia, any grade ≥3 non-hematologic clinical (non-laboratory) toxicity with exceptions per protocol, any grade 3 or grade 4 non-hematologic laboratory value if clinically significant medical intervention was required to treat the participant or the abnormality led to hospitalization, or the abnormality persisted for >7 days, and the abnormality resulted in a drug-induced liver injury (DILI) as defined by Hy's Law. Toxicities were graded for severity according to the National Cancer Institute-Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v5.0).	21 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	ORR was defined as the 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. CR was defined as all of the following: disappearance of all target and non-target tumor lesions, and reduction in short axis to <10 millimeters (mm) in all pathological target and non-target lesions. PR was defined as ≥30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	Up to approximately 2 years 5 months
Duration of Response (DOR)	DOR was 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.	Up to approximately 2 years 5 months
Disease Control Rate (DCR)	DCR was defined as the percentage of participants with BOR of CR, PR, and stable disease (SD) according to RECIST v1.1 as assessed by investigator. CR was defined as all of the following: disappearance of all target and non-target tumor lesions, and reduction in short axis to <10 millimeters (mm) in all pathological target and non-target lesions. PR was defined as ≥30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD).	Up to approximately 2 years 5 months
Progression Free Survival (PFS)	PFS was 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.	Up to approximately 2 years 5 months
Overall Survival (OS)	OS was 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.	Up to approximately 2 years 5 months
Number of Participants With Abscopal Response in Non-irradiated Target Lesions As Assessed by the Investigator	An abscopal response described radiotherapy (RT)-induced immune-mediated tumor regression at sites distant to the irradiated field. For the purpose of this trial, an abscopal response was defined as a reduction of at least 30% in diameter of the best responding unirradiated target lesion. Data are reported for the number of participants with abscopal response in non-irradiated target lesions as assessed by the investigator.	Up to approximately 2 years 5 months
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	An adverse event (AE) was 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 was therefore 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. A TEAE was any AE that occurred or worsened after the first dose of trial treatment. A summary of all Serious Adverse Events and Other Adverse Events (non-serious) regardless of causality is located in the 'Reported Adverse Events' Section.	Up to approximately 2 years 5 months
Blood Concentration of GEN1042 Over Time	Blood samples were collected for measurement of serum concentrations of GEN1042. Data are reported for Cycle (C)1 Day (D)1 pre-dose and end of infusion (EOI), C1D8, C1D15, C2D1 pre-dose and end of infusion, C2D8, C2D15, C3D1 pre-dose and end of infusion,C4D1 pre-dose and end of infusion,C4D8, C5D1 pre-dose and end of infusion, C7D1 pre-dose and end of infusion,C11D1 end of infusion,C12D1 end of infusion+2 hours,C15D1 end of infusion,C19D1 end of infusion,C23D1 end of infusion, End of Treatment (~D487) and Safety Follow Up (~D517). Cycles were 21 days in length.	At multiple timepoints (as described in the "Outcome Measure Description" field between Cycle 1 Day 1 up to Safety Follow Up [up to approximately Day 517]). Cycles were 21 days in length.
Number of Participants With Anti-drug Antibodies (ADAs)	Venous blood samples were drawn for analysis of ADAs. Data are reported for the number of participants with an on-treatment ADA status of positive. For on-treatment results, a participant was considered ADA positive if either 1) ADA was negative at baseline and at least one on-treatment result was positive 2) positive at baseline and at least one positive on-treatment result with at least one titer higher than baseline.	Up to approximately 2 years 5 months

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• Results Summary in Plain Language

Study record dates

Study Major Dates

• Study Start (Actual): March 8, 2023
• Primary Completion (Actual): August 11, 2025
• Study Completion (Actual): August 11, 2025

Study Registration Dates

• First Submitted: August 4, 2022
• First Submitted That Met QC Criteria: August 4, 2022
• First Posted (Actual): August 8, 2022

Study Record Updates

• Last Update Posted (Actual): August 12, 2026
• Last Update Submitted That Met QC Criteria: August 10, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: anti-CD40; DuoBody®
• Additional Relevant MeSH Terms: Therapeutics; Radiotherapy; pembrolizumab
• Other Study ID Numbers: GCT1042-02; 2022-000509-29 (EudraCT Number); 2023-508529-29-00 (Ctis); RECF-005058 (Registry Identifier: National Institute of Cancer France)

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