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

Phase 1

Recruiting

• Conditions: Select Advanced Solid Tumors
• Interventions: Drug: Brenetafusp and pembrolizumab; Drug: Brenetafusp and chemotherapy; Drug: Brenetafusp and tebentafusp; Drug: Brenetafusp and monoclonal antibodies and chemotherapy; Drug: Brenetafusp; Drug: Brenetafusp and bevacizumab; Drug: Brenetafusp and kinase inhibitors

• Registration Number: NCT04262466
• Lead Sponsor: Immunocore Ltd

Brief Summary

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.

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 Timeline

• Study First Submitted: 2020-01-30
• Study First Submitted QC: 2020-02-07
• Study First Posted: 2020-02-10
• Study Start: 2020-02-25
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-23
• Last Update Posted: 2024-10-26
• Primary Completion: 2026-02
• Study Completion: 2026-08

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 727

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
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 dose interruptions, dose reductions, or dose discontinuations	Up to ~12 months
Phase 1: Number of participants with abnormal laboratory test results (hematology)	Up to 30 days after the last dose of study therapy
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 1: Mean change from baseline in QTcF interval	Up to 30 days after the last dose of study therapy
Phase 2: Best overall response (BOR)	Up to ~2 years

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (76)

D'Or Institute for Research and Education; 🇧🇷 Rio de Janeiro, Brazil

National Cancer Institute; 🇧🇷 Rio De Janeiro, Brazil

Hospital Israelita Albert Einstein; 🇧🇷 São Paulo, Brazil

Institut Bergonie - Nouvelle-Aquitaine; 🇫🇷 Bordeaux, Gironde, France

Institut Curie; 🇫🇷 Paris, France

St Vincents University Hospital; 🇮🇪 Dublin, Ireland

Centre Hospitalier Universitaire Vaudois Lausanne; 🇨🇭 Lausanne, Switzerland

Guy's and St Thomas' NHS Foundation Trust; 🇬🇧 London, United Kingdom

University of California - San Diego; 🇺🇸 La Jolla, California, United States

Angeles Clinic and Research Institute; 🇺🇸 Los Angeles, California, United States

University of California Davis Comprehensive Center; 🇺🇸 Sacramento, California, United States

University of Colorado; 🇺🇸 Aurora, Colorado, United States

Georgetown University Medical Center; 🇺🇸 Washington, District of Columbia, United States

Houston Lee Moffitt Cancer Center & Research Institute; 🇺🇸 Tampa, Florida, United States

The University of Chicago Medical Center; 🇺🇸 Chicago, Illinois, United States

University of Iowa; 🇺🇸 Iowa City, Iowa, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

John Theurer Cancer Center at Hackensack University Medical Center; 🇺🇸 Hackensack, New Jersey, United States

Columbia University Medical Center; 🇺🇸 New York, New York, United States

Memorial Sloan Kettering; 🇺🇸 New York, New York, United States

University of Oklahoma Peggy and Charles Stephenson Cancer Center; 🇺🇸 Oklahoma City, Oklahoma, United States

Abramson Cancer Center of the University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

Thomas Jefferson University Hospital; 🇺🇸 Philadelphia, Pennsylvania, United States

UPMC Hillman Cancer Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

Prisma Health; 🇺🇸 Greenville, South Carolina, United States

Sarah Cannon Research Institute; 🇺🇸 Nashville, Tennessee, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

University of Utah - Huntsman Cancer Institute; 🇺🇸 Salt Lake City, Utah, United States

University of Washington - Fred Hutchinson Cancer Center; 🇺🇸 Seattle, Washington, United States

University of Wisconsin; 🇺🇸 Madison, Wisconsin, United States

Scientia Clinical Research; 🇦🇺 Randwick, New South Wales, Australia

Melanoma Institute Australia (MIA) - The Poche Centre; 🇦🇺 Wollstonecraft, New South Wales, Australia

The Alfred Hospital; 🇦🇺 Melbourne, Victoria, Australia

Linear Clinical Research; 🇦🇺 Nedlands, Western Australia, Australia

LKH - Universitätsklinikum der PMU Salzburg; 🇦🇹 Salzburg, Austria

Universitair Ziekenhuis Brussel; 🇧🇪 Jette, Brussel, Belgium

CHU de Liege; 🇧🇪 Liège, Luik, Belgium

Institut Jules Bordet; 🇧🇪 Bruxelles, Belgium

UZA; 🇧🇪 Edegem, Belgium

Universitair Ziekenhuis Gent; 🇧🇪 Gent, Belgium

UZ Leuven; 🇧🇪 Leuven, Belgium

Hospital Nossa Senhora da Conceicao; 🇧🇷 Porto Alegre, Brazil

Princess Margaret Cancer Centre; 🇨🇦 Toronto, Ontario, Canada

CHUM Centre de Recherche; 🇨🇦 Montréal, Quebec, Canada

Gustave Roussy (Institut de Cancerologie Gustave-Roussy); 🇫🇷 Villejuif, Val De Marne, France

Universite Claude Bernard Lyon Est; 🇫🇷 Lyon, Villeurbanne, France

Hopital Saint-Louis - Centre d'Onco-Dermatologie; 🇫🇷 Paris, France

Universitaetsklinikum Heidelberg; 🇩🇪 Heidelberg, Germany

Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Dipartimento di Medicina Interna e Scienze Mediche; 🇮🇹 Rome, Roma, Italy

Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Patologia Ostetrica e Ginecologica; 🇮🇹 Seriate, Roma, Italy

Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale; 🇮🇹 Napoli, Italy

Seoul National University Hospital; 🇰🇷 Seoul, Korea, Republic of

Yonsei University College of Medicine; 🇰🇷 Seoul, Korea, Republic of

University of Ulsan College of Medicine; 🇰🇷 Seoul, Korea, Republic of

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of

Netherlands Cancer Institute; 🇳🇱 Amsterdam, CX, Netherlands

UMC Groningen Comprehensive Cancer Center; 🇳🇱 Groningen, GZ, Netherlands

Leiden UMC; 🇳🇱 Leiden, ZA, Netherlands

New Zealand Clinical Research-Auckland; 🇳🇿 Auckland, New Zealand

Centrum Medyczne Pratia Poznan - Skorzewo; 🇵🇱 Skórzewo, Poland

Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy; 🇵🇱 Warszawa, Poland

Universidad de Navarra - Clinica Universidad de Navarra (CUN) - Pamplona; 🇪🇸 Pamplona, Navarra, Spain

NEXT Barcelona; 🇪🇸 Barcelona, Spain

Hospital Universitario Vall dHebron; 🇪🇸 Barcelona, Spain

Hospital Duran i Reynals; 🇪🇸 Barcelona, Spain

Universidad de Navarra - Clinica Universidad de Navarra (CUN) - Madrid; 🇪🇸 Madrid, Spain

Hospital Universitario Fundacion Jimenez Diaz; 🇪🇸 Madrid, Spain

University Hospital, Basel Switzerland; 🇨🇭 Basel, Switzerland

University Hospital of Zurich; 🇨🇭 Zürich, Switzerland

Sarah Cannon Research Institute UK; 🇬🇧 London, City Of London, United Kingdom

University of Oxford; 🇬🇧 Oxford, Oxfordshire, United Kingdom

The Beatson West of Scotland Cancer Centre; 🇬🇧 Glasgow, Scotland, United Kingdom

University of Liverpool; 🇬🇧 Liverpool, United Kingdom

University College Hospital London; 🇬🇧 London, United Kingdom

The Christie NHS Foundation Trust; 🇬🇧 Manchester, United Kingdom

Royal Marsden Hospital; 🇬🇧 Surrey Quays, United Kingdom