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

Phase 1/2 Study of IMC-F106C in Advance PRAME-Positive Cancers

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 participants who have the appropriate HLA-A2 tissue marker and whose cancer is positive for PRAME.

Study Overview

• Status: Active, not recruiting
• Conditions: Select Advanced Solid Tumors
• Intervention / Treatment: Drug: Brenetafusp; Drug: Brenetafusp and pembrolizumab; Drug: Brenetafusp and chemotherapy; Drug: Brenetafusp and tebentafusp; Drug: Brenetafusp and bevacizumab; Drug: Brenetafusp and kinase inhibitors; Drug: Brenetafusp and monoclonal antibodies and chemotherapy

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 410
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, 2031
      • Scientia Clinical Research
    • Wollstonecraft, New South Wales, Australia, 2065
      • Melanoma Institute Australia (MIA) - The Poche Centre
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Linear Clinical Research
• Austria
  • Salzburg, Austria, 5020
    • LKH - Universitätsklinikum der PMU Salzburg
• Belgium
  • Brussels, Belgium, 1070
    • Institut Jules Bordet
  • Edegem, Belgium, 2650
    • UZA
  • Ghent, Belgium, 9000
    • Universitair Ziekenhuis Gent
  • Leuven, Belgium, 3000
    • UZ Leuven
  • Brussels Capital
    • Jette, Brussels Capital, Belgium, 1090
      • Universitair Ziekenhuis Brussel
  • Luik
    • Liège, Luik, Belgium, 4000
      • CHU de Liège
• Brazil
  • Porto Alegre, Brazil, 91350-200
    • Hospital Nossa Senhora da Conceição
  • Rio de Janeiro, Brazil
    • D'OR Institute for Research and Education
  • Rio de Janeiro, Brazil
    • National Cancer Institute
  • São Paulo, Brazil
    • Hospital Israelita Albert Einstein
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • Princess Margaret Cancer Centre
  • Quebec
    • Montreal, Quebec, Canada, H2X 0A9
      • CHUM Centre de Recherche
• France
  • Paris, France
    • Institut Curie
  • Paris, France, 75010
    • Hopital Saint-Louis - Centre d'Onco-Dermatologie
  • Gironde
    • Bordeaux, Gironde, France
      • Institut Bergonie - Nouvelle-Aquitaine
  • Val De Marne
    • Villejuif, Val De Marne, France, 94805
      • Gustave Roussy (Institut de Cancerologie Gustave-Roussy)
  • Villeurbanne
    • Lyon, Villeurbanne, France, 69100
      • Universite Claude Bernard Lyon Est
• Germany
  • Heidelberg, Germany, 69120
    • Universitaetsklinikum Heidelberg
• Ireland
  • Dublin, Ireland
    • St Vincents University Hospital
• Italy
  • Napoli, Italy, 80131
    • Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale
  • Roma
    • Rome, Roma, Italy, 00168
      • Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Dipartimento di Medicina Interna e Scienze Mediche
    • Seriate, Roma, Italy, 00168
      • Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Patologia Ostetrica e Ginecologica
• Netherlands
  • CX
    • Amsterdam, CX, Netherlands, 1066
      • Netherlands Cancer Institute
  • GZ
    • Groningen, GZ, Netherlands, 9713
      • UMC Groningen Comprehensive Cancer Center
  • ZA
    • Leiden, ZA, Netherlands, 2333
      • Leiden UMC
• New Zealand
  • Auckland, New Zealand, 92697
    • New Zealand Clinical Research-Auckland
• Poland
  • Skórzewo, Poland, 60-185
    • Centrum Medyczne Pratia Poznan - Skorzewo
  • Warsaw, Poland, 02-781
    • Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy
• South Korea
  • Seoul, South Korea, 03080
    • Seoul National University Hospital
  • Seoul, South Korea, 06351
    • Samsung Medical Center
  • Seoul, South Korea, 03722
    • Yonsei University College of Medicine
  • Seoul, South Korea, 05505
    • University of Ulsan College of Medicine
• Spain
  • Barcelona, Spain, 08908
    • Hospital Duran i Reynals
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall dHebron
  • Barcelona, Spain, 08023
    • NEXT Barcelona
  • Madrid, Spain, 28040
    • Hospital Universitario Fundación Jimenez Díaz
  • Madrid, Spain, 28022
    • Universidad de Navarra - Clinica Universidad de Navarra (CUN) - Madrid
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Universidad de Navarra - Clinica Universidad de Navarra (CUN) - Pamplona
• Switzerland
  • Basel, Switzerland, 4031
    • University Hospital, Basel Switzerland
  • Lausanne, Switzerland
    • Centre Hospitalier Universitaire Vaudois Lausanne
  • Zurich, Switzerland, 8058
    • University Hospital of Zürich
• United Kingdom
  • Liverpool, United Kingdom, L69 3BX
    • University of Liverpool
  • London, United Kingdom
    • Guy's and St Thomas' NHS Foundation Trust
  • London, United Kingdom, W1T7HA
    • University College Hospital London
  • Manchester, United Kingdom
    • The Christie NHS Foundation Trust
  • Surrey Quays, United Kingdom, SM25PT
    • Royal Marsden Hospital
  • City of London
    • London, City of London, United Kingdom, W1G6AD
      • Sarah Cannon Research Institute UK
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX3 7LI
      • University of Oxford
  • Scotland
    • Glasgow, Scotland, United Kingdom, G12 0YN
      • The Beatson West of Scotland Cancer Centre
• United States
  • California
    • La Jolla, California, United States, 92093
      • University of California - San Diego
    • Los Angeles, California, United States, 90025
      • Angeles Clinic and Research Institute
    • Sacramento, California, United States, 95817
      • University of California Davis Comprehensive Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20057
      • Georgetown University Medical Center
  • Florida
    • Tampa, Florida, United States, 33612
      • Houston Lee Moffitt Cancer Center & Research Institute
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago Medical Center
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • John Theurer Cancer Center at Hackensack University Medical Center
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Peggy and Charles Stephenson Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Abramson Cancer Center of the University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Hillman Cancer Center
  • South Carolina
    • Greenville, South Carolina, United States, 92697
      • Prisma Health
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Texas
    • Houston, Texas, United States, 77030
      • Md Anderson Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah - Huntsman Cancer Institute
  • Washington
    • Seattle, Washington, United States, 98109
      • University of Washington - Fred Hutchinson Cancer Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

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

Description

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 (Participants 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 participants
16. Any other contraindication for applicable combination partner based on local prescribing information

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

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Brenetafusp Monotherapy; Participants receive brenetafusp.	Drug: Brenetafusp; Brenetafusp IV infusions
Experimental: Brenetafusp and Anti-PD(L)1 Agent; Participants receive brenetafusp and pembrolizumab.	Drug: Brenetafusp and pembrolizumab; Brenetafusp and pembrolizumab IV infusions
Experimental: Brenetafusp and Chemotherapy; Participants receive brenetafusp and chemotherapy. Choice of chemotherapy is dependent on cohort.	Drug: Brenetafusp and chemotherapy; Brenetafusp and chemotherapy IV infusions
Experimental: Brenetafusp and Targeted Therapy; Participants receive brenetafusp and a selected targeted therapy. Receipt of kinase inhibitor is dependent on histology.	Drug: Brenetafusp and tebentafusp; Brenetafusp and tebentafusp IV infusions; Drug: Brenetafusp and bevacizumab; Brenetafusp and bevacizumab IV infusions; Drug: Brenetafusp and kinase inhibitors; Brenetafusp and oral kinase inhibitors
Experimental: Brenetafusp and Multimodal Therapy; Participants receive brenetafusp, biologics (eg, pembrolizumab, bevacizumab) IV infusions and chemotherapy IV infusions based on histology.	Drug: Brenetafusp and monoclonal antibodies and chemotherapy; Brenetafusp and a monoclonal antibody therapy and chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Phase 1: Incidence of dose-limiting toxicity (DLT)s	Up to ~28 days after each dose
Phase 1: Incidence of adverse events (AE) and serious adverse events (SAE)	Up to 30 days after the last dose of study therapy
Phase 1: Number of participants with abnormal laboratory test results (hematology)	Up to 30 days after the last dose of study therapy
Phase 1: Mean change from baseline in QTcF interval	Up to 30 days after the last dose of study therapy
Phase 1: Number of participants with dose interruptions, dose reductions, or dose discontinuations	Up to ~12 months
Phase 1: Number of participants with abnormal laboratory test results (chemistry)	Up to 30 days after the last dose of study therapy
Phase 1: Number of participants with abnormal laboratory test results (coagulation)	Up to 30 days after the last dose of study therapy
Phase 1: Number of participants with abnormal urinalysis	Up to 30 days after the last dose of study therapy
Phase 1: Number of participants with abnormal vital signs	Up to 30 days after the last dose of study therapy
Phase 2: Best overall response (BOR)	Up to ~2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Phase I: Best Overall Response (BOR)	Up to ~2 years
Progression-free survival (PFS)	Up to ~2 years
Duration of response (DOR)	Up to ~2 years
Overall survival	Up to ~2 years
Area under the plasma concentration-time curve (AUC) of brenetafusp	At designated time points up to ~3 weeks
Maximum plasma drug concentration (Cmax) of brenetafusp	At designated time points up to ~3 weeks
Time to reach maximum plasma concentration (Tmax) of brenetafusp	At designated time points up to ~3 weeks
Plasma elimination half-life (t½) of brenetafusp	At designated time points up to ~3 weeks
Incidence of anti-brenetafusp antibody formation	Up to ~ 2 years
Changes in lymphocyte counts over time	Up to ~3 weeks
Changes in serum cytokines over time	Up to ~3 weeks
Local tumor response based on Gynecological Cancer Intergroup (GCIG) Cancer Antigen 25 (CA-125) response criteria	Up to ~2 years

Collaborators and Investigators

• Sponsor: Immunocore Ltd
• Investigators: Study Director: Shaad Abdullah, MD, Immunocore Ltd

Study record dates

Study Major Dates

• Study Start (Actual): February 25, 2020
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: January 30, 2020
• First Submitted That Met QC Criteria: February 7, 2020
• First Posted (Actual): February 10, 2020

Study Record Updates

• Last Update Posted (Actual): March 6, 2026
• Last Update Submitted That Met QC Criteria: March 4, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Lung Cancer; NSCLC; Checkpoint inhibitor; Immunotherapy; Melanoma; Ovarian Cancer; ImmTAC; Bispecific T cell receptor fusion protein; Immune mobilizing monoclonal T cell receptor against cancer; PD1 / PD-1; PD-L1 / PDL1; Endometrial Cancer; Triple Negative Breast Cancer
• Additional Relevant MeSH Terms: Amino Acids, Peptides, and Proteins; Proteins; Therapeutics; Antibodies, Monoclonal, Humanized; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Bevacizumab; Antibodies, Monoclonal; pembrolizumab; Drug Therapy; tebentafusp
• Other Study ID Numbers: IMC-F106C-101

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.: No