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

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 IMC-F106C in adult patients who have the appropriate HLA-A2 tissue marker and whose cancer is positive for PRAME.

Study Overview

• Status: Recruiting
• Conditions: Select Advanced Solid Tumors
• Intervention / Treatment: Drug: IMC-F106C; Drug: IMC-F106C and pembrolizumab; Drug: IMC-F106C and chemotherapy; Drug: IMC-F106C and tebentafusp; Drug: IMC-F106C and bevacizumab; Drug: IMC-F106C and kinase inhibitors; Drug: IMC-F106C 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 IMC-F106C as a single agent and administered in combination with chemotherapies, targeted therapies, and monoclonal antibodies.
2. Phase 2: To assess the efficacy of IMC-F106C in selected advanced solid tumors.

• Study Type: Interventional
• Enrollment (Estimated): 727
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Immunocore Medical Information; Phone Number: 844-466-8661; Email: medical.information@immunocore.com
• Study Contact Backup: Name: Immunocore Medical Information EU; Phone Number: +00 800-744-51111; Email: medinfo.eu@immunocore.com

Study Locations

• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, 2031
      • Recruiting
      • Scientia Clinical Research
    • Wollstonecraft, New South Wales, Australia, 2065
      • Recruiting
      • Melanoma Institute Australia (MIA) - The Poche Centre
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Recruiting
      • The Alfred Hospital
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Recruiting
      • Linear Clinical Research
• Austria
  • Salzburg, Austria, 5020
    • Recruiting
    • LKH - Universitätsklinikum der PMU Salzburg
• Belgium
  • Bruxelles, Belgium, 1070
    • Recruiting
    • Institut Jules Bordet
  • Edegem, Belgium, 2650
    • Recruiting
    • UZA
  • Gent, Belgium, 9000
    • Recruiting
    • Universitair Ziekenhuis Gent
  • Leuven, Belgium, 3000
    • Recruiting
    • UZ Leuven
  • Brussel
    • Jette, Brussel, Belgium, 1090
      • Recruiting
      • Universitair Ziekenhuis Brussel
  • Luik
    • Liège, Luik, Belgium, 4000
      • Recruiting
      • CHU de Liège
• Brazil
  • Porto Alegre, Brazil, 91350-200
    • Recruiting
    • Hospital Nossa Senhora Da Conceicao
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • Recruiting
      • Princess Margaret Cancer Centre
  • Quebec
    • Montréal, Quebec, Canada, H2X 0A9
      • Recruiting
      • CHUM Centre de Recherche
• France
  • Paris, France, 75010
    • Recruiting
    • Hopital Saint-Louis - Centre d'Onco-Dermatologie
  • Val De Marne
    • Villejuif, Val De Marne, France, 94805
      • Recruiting
      • Gustave Roussy (Institut de Cancerologie Gustave-Roussy)
  • Villeurbanne
    • Lyon, Villeurbanne, France, 69100
      • Recruiting
      • Universite Claude Bernard Lyon Est
• Germany
  • Heidelberg, Germany, 69120
    • Recruiting
    • Universitaetsklinikum Heidelberg
• Italy
  • Napoli, Italy, 80131
    • Recruiting
    • Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale
  • Roma
    • Rome, Roma, Italy, 00168
      • Recruiting
      • Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Dipartimento di Medicina Interna e Scienze Mediche
    • Seriate, Roma, Italy, 00168
      • Recruiting
      • Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Patologia Ostetrica e Ginecologica
• Korea, Republic of
  • Seoul, Korea, Republic of, 03722
    • Recruiting
    • Yonsei University College of Medicine
  • Seoul, Korea, Republic of, 03080
    • Recruiting
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 06351
    • Recruiting
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 05505
    • Recruiting
    • University of Ulsan College of Medicine
• Netherlands
  • CX
    • Amsterdam, CX, Netherlands, 1066
      • Recruiting
      • Netherlands Cancer Institute
  • GZ
    • Groningen, GZ, Netherlands, 9713
      • Recruiting
      • UMC Groningen Comprehensive Cancer Center
  • ZA
    • Leiden, ZA, Netherlands, 2333
      • Recruiting
      • Leiden UMC
• New Zealand
  • Auckland, New Zealand, 92697
    • Recruiting
    • New Zealand Clinical Research-Auckland
• Poland
  • Skórzewo, Poland, 60-185
    • Recruiting
    • Centrum Medyczne Pratia Poznan - Skorzewo
  • Warszawa, Poland, 02-781
    • Recruiting
    • Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitario Vall Dhebron
  • Barcelona, Spain, 08908
    • Recruiting
    • Hospital Duran I Reynals
  • Barcelona, Spain, 08023
    • Recruiting
    • NEXT Barcelona
  • Madrid, Spain, 28040
    • Recruiting
    • Hospital Universitario Fundacion Jimenez Diaz
  • Madrid, Spain, 28022
    • Recruiting
    • Universidad de Navarra - Clinica Universidad de Navarra (CUN) - Madrid
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Recruiting
      • Universidad de Navarra - Clinica Universidad de Navarra (CUN) - Pamplona
• Switzerland
  • Basel, Switzerland, 4031
    • Recruiting
    • University Hospital, Basel Switzerland
  • Zürich, Switzerland, 8058
    • Recruiting
    • University Hospital of Zürich
• United Kingdom
  • Liverpool, United Kingdom, L69 3BX
    • Recruiting
    • University of Liverpool
  • London, United Kingdom, W1T7HA
    • Recruiting
    • University College Hospital London
    • Contact: Shazia Begum
  • Manchester, United Kingdom
    • Recruiting
    • The Christie NHS Foundation Trust
    • Contact: Jessica Ritchie
    • Contact: Schweta Vyas
    • Principal Investigator: Fiona Thistlethwaite
  • Surrey Quays, United Kingdom, SM25PT
    • Recruiting
    • Royal Marsden Hospital
    • Contact: Dan Bar
    • Contact: Mahesha Ganegoda
    • Principal Investigator: Juanita Lopez, MD
  • City Of London
    • London, City Of London, United Kingdom, W1G6AD
      • Recruiting
      • Sarah Cannon Research Institute UK
      • Contact: Maria Victoria Borja Beral
      • Contact: Juan Pedro Navarro Garcia
      • Principal Investigator: Anja Williams, MD
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX3 7LI
      • Recruiting
      • University of Oxford
  • Scotland
    • Glasgow, Scotland, United Kingdom, G12 0YN
      • Recruiting
      • The Beatson West of Scotland Cancer Centre
• United States
  • California
    • La Jolla, California, United States, 92093
      • Recruiting
      • University of California - San Diego
    • Los Angeles, California, United States, 90025
      • Recruiting
      • Angeles Clinic and Research Institute
      • Contact: Roland Menendez
    • Sacramento, California, United States, 95817
      • Recruiting
      • University of California Davis Comprehensive Center
      • Contact: Laura Molnar
      • Contact: Frances Lara
      • Principal Investigator: Hui Amy Chen, MD
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado
  • District of Columbia
    • Washington, District of Columbia, United States, 20057
      • Recruiting
      • Georgetown University Medical Center
  • Florida
    • Tampa, Florida, United States, 33612
      • Recruiting
      • Houston Lee Moffitt Cancer Center & Research Institute
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • The University of Chicago Medical Center
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Michael Cournoyer; Email: MCOURNOYER@mgh.harvard.edu
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Recruiting
      • John Theurer Cancer Center at Hackensack University Medical Center
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Medical Center
      • Contact: Suzanne Mistretta
      • Contact: Elizabeth Vann
      • Principal Investigator: Benjamin Izar, MD
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering
      • Contact: Samantha Smith
      • Principal Investigator: Margaret Callahan, MD
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Recruiting
      • University of Oklahoma Peggy and Charles Stephenson Cancer Center
      • Contact: Sarah Homan
      • Contact: Kiersten During
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Abramson Cancer Center of the University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Thomas Jefferson University Hospital
      • Contact: Kathrine Senter
      • Contact: Taylor Holton
      • Principal Investigator: Takami Sato, MD
    • Pittsburgh, Pennsylvania, United States, 15232
      • Recruiting
      • UPMC Hillman Cancer Center
      • Contact: Sarah Brodeur
      • Principal Investigator: Diwakar Davar, MD
  • South Carolina
    • Greenville, South Carolina, United States, 92697
      • Recruiting
      • Prisma Health
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Sarah Cannon Research Institute
      • Contact: Whitney Burroughs
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center
      • Contact: Jeane Painter
      • Contact: Jessica Catrett
      • Principal Investigator: Ectaerina Dumbrava, MD
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Recruiting
      • University of Utah - Huntsman Cancer Institute
  • Washington
    • Seattle, Washington, United States, 98109
      • Recruiting
      • University of Washington - Fred Hutchinson Cancer Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • Recruiting
      • 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 (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

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: IMC-F106C Monotherapy; Participants receive IMC-F106C.	Drug: IMC-F106C; IMC-F106C IV infusions
Experimental: IMC-F106C and Anti-PD(L)1 Agent; Participants receive IMC-F106C and pembrolizumab.	Drug: IMC-F106C and pembrolizumab; IMC-F106C and pembrolizumab IV infusions
Experimental: IMC-F106C and Chemotherapy; Participants receive IMC-F106C and chemotherapy. Choice of chemotherapy is dependent on cohort.	Drug: IMC-F106C and chemotherapy; IMC-F106C and chemotherapy IV infusions
Experimental: IMC-F106C and Targeted Therapy; Participants receive IMC-F106C and a selected targeted therapy. Receipt of kinase inhibitor is dependent on histology.	Drug: IMC-F106C and tebentafusp; IMC-F106C and tebentafusp IV infusions; Drug: IMC-F106C and bevacizumab; IMC-F106C and bevacizumab IV infusions; Drug: IMC-F106C and kinase inhibitors; IMC-F106C and oral kinase inhibitors
Experimental: IMC-F106C and Multimodal Therapy; Participants receive IMC-F106C, biologics (eg, pembrolizumab, bevacizumab) IV infusions and chemotherapy IV infusions based on histology.	Drug: IMC-F106C and monoclonal antibodies and chemotherapy; IMC-F106C and a monoclonal antibody therapy and chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Phase 2: Best overall response (BOR)	from first dose to approximately 2 years
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	from first dose through last dose (anticipated for 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)	from first dose to 30 days after the last dose
Phase 1: Number of participants with abnormal laboratory test results (coagulation)	from first dose to 30 days after the last dose
Phase 1: Number of participants with abnormal urinalysis	from first dose to 30 days after the last dose
Phase 1: Number of participants with abnormal vital signs	from first dose to 30 days after the last dose
Phase 1: Mean change from baseline in QTcF interval	Up to 30 days after the last dose of study therapy

Secondary Outcome Measures

Outcome Measure	Time Frame
Phase I: Best Overall Response (BOR)	from first dose to approximately 2 years
Progression-free survival (PFS)	from first dose to approximately 2 years
Duration of response (DOR)	from first dose to approximately 2 years
Overall survival	from first dose to approximately 2 years
Pharmacokinetics Area under the plasma concentration-time curve (AUC)	approximately 3 weeks (IMC-F106C AUC will be assessed for ~3 weeks)
Pharmacokinetics The maximum observed plasma drug concentration (Cmax)	approximately 3 weeks (IMC-F106C Cmax will be assessed for ~3 weeks)
Pharmacokinetics The time to reach maximum plasma concentration (Tmax)	approximately 3 weeks (IMC-F106C Tmax will be assessed for ~3 weeks)
Pharmacokinetics The elimination half-life (t1/2)	approximately 3 weeks (IMC-F106C t1/2 will be assessed for ~ 3 weeks)
Incidence of anti-IMC-F106C antibody formation	approximately 2 years
Changes in lymphocyte counts over time	approximately 3 weeks
Changes in serum cytokines over time	approximately 3 weeks
Local tumor response based on Gynecological Cancer Intergroup (GCIG) Cancer Antigen 25 (CA-125) response criteria	approximately 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): June 1, 2026
• Study Completion (Estimated): June 1, 2026

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): April 2, 2024
• Last Update Submitted That Met QC Criteria: March 28, 2024
• Last Verified: March 1, 2024

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: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Immune Checkpoint Inhibitors; Antibodies; Bevacizumab; Pembrolizumab; Antibodies, Monoclonal
• 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