Safety and Efficacy of IMC-F106C as a Single Agent and in Combination With Checkpoint Inhibitors

Immunocore

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Select Advanced Solid Tumors

Treatments: Drug: Brenetafusp and kinase inhibitors; Drug: Brenetafusp and monoclonal antibodies and chemotherapy; Drug: Brenetafusp and chemotherapy; Drug: Brenetafusp and tebentafusp; Drug: Brenetafusp and bevacizumab; Drug: Brenetafusp; Drug: Brenetafusp and pembrolizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT04262466

IMC-F106C-101

Details and patient eligibility

About

Brenetafusp (IMC-F106C) is an immune-mobilizing monoclonal T cell receptor against cancer (ImmTAC ®) designed for the treatment of cancers positive for the tumor-associated antigen PRAME. This is a first-in-human trial designed to evaluate the safety and efficacy of brenetafusp in adult patients who have the appropriate HLA-A2 tissue marker and whose cancer is positive for PRAME.

Full description

The IMC-F106C-101 Phase 1/2 study will be evaluated in patients with metastatic/unresectable tumors which include select Advanced Solid Tumors and will be conducted in two phases.

1. Phase 1: To identify the Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 dose (RP2D) of brenetafusp as a single agent and administered in combination with chemotherapies, targeted therapies, and monoclonal antibodies.
2. Phase 2: To assess the efficacy of brenetafusp in selected advanced solid tumors.

Enrollment: 727 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. ECOG PS 0 or 1
2. HLA-A*02:01 positive
3. PRAME positive tumor
4. Relapsed from, refractory to, or intolerant of standard therapies; or, in combination with standard therapies
5. If applicable, must agree to use highly effective contraception

Exclusion criteria

1. Symptomatic or untreated central nervous system metastasis
2. Recent bowel obstruction
3. Ongoing ascites or effusion requiring recent drainages
4. Significant immune-mediated adverse event with prior immunotherapy (patients in checkpoint inhibitor combination treatment)
5. Inadequate washout from prior anticancer therapy
6. Significant ongoing toxicity from prior anticancer treatment
7. Out-of-range laboratory values
8. Clinically significant lung, heart, or autoimmune disease
9. Ongoing requirement for immunosuppressive treatment
10. Prior solid organ or bone marrow transplant
11. Active hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection
12. Significant secondary malignancy
13. Hypersensitivity to study drug or excipients
14. Antibiotics, vaccines or surgery within 2-4 weeks prior to the first dose of study intervention
15. Pregnant or lactating
16. Any other contraindication for applicable combination partner based on local prescribing information

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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727 participants in 5 patient groups

Brenetafusp Monotherapy

Experimental group

Description:

Participants receive brenetafusp.

Treatment:

Drug: Brenetafusp

Brenetafusp and Anti-PD(L)1 Agent

Experimental group

Description:

Participants receive brenetafusp and pembrolizumab.

Treatment:

Drug: Brenetafusp and pembrolizumab

Brenetafusp and Chemotherapy

Experimental group

Description:

Participants receive brenetafusp and chemotherapy. Choice of chemotherapy is dependent on cohort.

Treatment:

Drug: Brenetafusp and chemotherapy

Brenetafusp and Targeted Therapy

Experimental group

Description:

Participants receive brenetafusp and a selected targeted therapy. Receipt of kinase inhibitor is dependent on histology.

Treatment:

Drug: Brenetafusp and bevacizumab

Drug: Brenetafusp and kinase inhibitors

Drug: Brenetafusp and tebentafusp

Brenetafusp and Multimodal Therapy

Experimental group

Description:

Participants receive brenetafusp, biologics (eg, pembrolizumab, bevacizumab) IV infusions and chemotherapy IV infusions based on histology.

Treatment:

Drug: Brenetafusp and monoclonal antibodies and chemotherapy