Clinical trial NCT05491317: A Safety and Antitumor Activity Trial of Immunoradiotherapy Combinations as a Treatment Option for Subjects With Metastatic Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Non-CNS Tumor
Lead sponsor: Genmab
Sponsor class: INDUSTRY
Collaborators: name: BioNTech SE
First posted: 2022-08-08
Enrollment: 88
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Part 1 is sequential, Part 2 is parallel (randomized)
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Part 1: Number of Participants with Dose Limiting Toxicities (DLTs)
timeFrame: During the first cycle (Cycle length = 21 days)
measure: Part 2: Number of Participants with Abscopal Response in Non-irradiated Target Lesions
timeFrame: Up to 12 months after the last radiation treatment
Secondary outcomes:
measure: Parts 1 and 2: Objective Response Rate (ORR)
timeFrame: Up to 2 years
measure: Parts 1 and 2: Duration of Response (DOR)
timeFrame: Up to 2 years
measure: Parts 1 and 2: Disease Control Rate (DCR)
timeFrame: Up to 2 years
measure: Parts 1 and 2: Progression Free Survival (PFS)
timeFrame: Up to 2 years
measure: Parts 1 and 2: One- year Overall Survival (OS)
timeFrame: Up to 2 years
measure: Part 1: Number of Participants With Abscopal Response in Non-irradiated Target Lesions
timeFrame: Up to 12 months after the last radiation treatment
measure: Parts 1 and 2: Number of Participants with Adverse Events (AEs)
timeFrame: From screening until the end of the safety follow-up period (30 days or 90 days after last dose)
measure: Parts 1 and 2: Area Under the Concentration-time Curve (AUC) of GEN1042
timeFrame: Predose and postdose at multiple timepoints up to 30 days after last dose
measure: Parts 1 and 2: Maximum (Peak) Plasma Concentration (Cmax)
timeFrame: Predose and postdose at multiple timepoints up to 30 days after last dose
measure: Parts 1 and 2: Elimination Half-life (T1/2) of GEN1042
timeFrame: Predose and postdose at multiple timepoints up to 30 days after last dose
measure: Parts 1 and 2: Number of Participants with Anti-drug Antibodies (ADAs)
timeFrame: Predose at multiple timepoints up to 30 days after last dose
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Institut Bergonie
city: Lyon
country: France
facility: Centre Leon Berard
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: Genmab
name: Study Official
role: STUDY_DIRECTOR
References: