Clinical trial NCT04262466: Safety and Efficacy of IMC-F106C as a Single Agent and in Combination With Checkpoint Inhibitors
Official title: Phase 1/2 Study of IMC-F106C in Advance PRAME-Positive Cancers
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Select Advanced Solid Tumors
Lead sponsor: Immunocore Ltd
Sponsor class: INDUSTRY
First posted: 2020-02-10
Enrollment: 727
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Phase 1: Incidence of dose-limiting toxicity (DLT)s
timeFrame: Up to ~28 days after each dose
measure: Phase 1: Incidence of adverse events (AE) and serious adverse events (SAE)
timeFrame: Up to 30 days after the last dose of study therapy
measure: Phase 1: Number of participants with dose interruptions, dose reductions, or dose discontinuations
timeFrame: Up to ~12 months
measure: Phase 1: Number of participants with abnormal laboratory test results (hematology)
timeFrame: Up to 30 days after the last dose of study therapy
measure: Phase 1: Number of participants with abnormal laboratory test results (chemistry)
timeFrame: Up to 30 days after the last dose of study therapy
measure: Phase 1: Number of participants with abnormal laboratory test results (coagulation)
timeFrame: Up to 30 days after the last dose of study therapy
measure: Phase 1: Number of participants with abnormal urinalysis
timeFrame: Up to 30 days after the last dose of study therapy
measure: Phase 1: Number of participants with abnormal vital signs
timeFrame: Up to 30 days after the last dose of study therapy
measure: Phase 1: Mean change from baseline in QTcF interval
timeFrame: Up to 30 days after the last dose of study therapy
measure: Phase 2: Best overall response (BOR)
timeFrame: Up to ~2 years
Secondary outcomes:
measure: Phase I: Best Overall Response (BOR)
timeFrame: Up to ~2 years
measure: Progression-free survival (PFS)
timeFrame: Up to ~2 years
measure: Duration of response (DOR)
timeFrame: Up to ~2 years
measure: Overall survival
timeFrame: Up to ~2 years
measure: Area under the plasma concentration-time curve (AUC) of brenetafusp
timeFrame: At designated time points up to ~3 weeks
measure: Maximum plasma drug concentration (Cmax) of brenetafusp
timeFrame: At designated time points up to ~3 weeks
measure: Time to reach maximum plasma concentration (Tmax) of brenetafusp
timeFrame: At designated time points up to ~3 weeks
measure: Plasma elimination half-life (t½) of brenetafusp
timeFrame: At designated time points up to ~3 weeks
measure: Incidence of anti-brenetafusp antibody formation
timeFrame: Up to ~ 2 years
measure: Changes in lymphocyte counts over time
timeFrame: Up to ~3 weeks
measure: Changes in serum cytokines over time
timeFrame: Up to ~3 weeks
measure: Local tumor response based on Gynecological Cancer Intergroup (GCIG) Cancer Antigen 25 (CA-125) response criteria
timeFrame: Up to ~2 years
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California - San Diego
state: California
city: Los Angeles
country: United States
facility: Angeles Clinic and Research Institute
state: California
city: Sacramento
country: United States
facility: University of California Davis Comprehensive Center
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Tampa
country: United States
facility: Houston Lee Moffitt Cancer Center & Research Institute
state: Florida
city: Chicago
country: United States
facility: The University of Chicago Medical Center
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering
state: New York
city: Oklahoma City
country: United States
facility: University of Oklahoma Peggy and Charles Stephenson Cancer Center
state: Oklahoma
city: Philadelphia
country: United States
facility: Abramson Cancer Center of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
city: Greenville
country: United States
facility: Prisma Health
state: South Carolina
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah - Huntsman Cancer Institute
state: Utah
city: Seattle
country: United States
facility: University of Washington - Fred Hutchinson Cancer Center
state: Washington
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Randwick
country: Australia
facility: Scientia Clinical Research
state: New South Wales
city: Wollstonecraft
country: Australia
facility: Melanoma Institute Australia (MIA) - The Poche Centre
state: New South Wales
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Nedlands
country: Australia
facility: Linear Clinical Research
state: Western Australia
city: Salzburg
country: Austria
facility: LKH - Universitätsklinikum der PMU Salzburg
city: Jette
country: Belgium
facility: Universitair Ziekenhuis Brussel
state: Brussel
city: Liège
country: Belgium
facility: CHU de Liege
state: Luik
city: Bruxelles
country: Belgium
facility: Institut Jules Bordet
city: Edegem
country: Belgium
facility: UZA
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Leuven
country: Belgium
facility: UZ Leuven
city: Porto Alegre
country: Brazil
facility: Hospital Nossa Senhora da Conceicao
city: Rio de Janeiro
country: Brazil
facility: D'Or Institute for Research and Education
city: Rio De Janeiro
country: Brazil
facility: National Cancer Institute
city: São Paulo
country: Brazil
facility: Hospital Israelita Albert Einstein
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Montréal
country: Canada
facility: CHUM Centre de Recherche
state: Quebec
city: Bordeaux
country: France
facility: Institut Bergonie - Nouvelle-Aquitaine
state: Gironde
city: Villejuif
country: France
facility: Gustave Roussy (Institut de Cancerologie Gustave-Roussy)
state: Val De Marne
city: Lyon
country: France
facility: Universite Claude Bernard Lyon Est
state: Villeurbanne
city: Paris
country: France
facility: Hopital Saint-Louis - Centre d'Onco-Dermatologie
city: Paris
country: France
facility: Institut Curie
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg
city: Dublin
country: Ireland
facility: St Vincents University Hospital
city: Rome
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Dipartimento di Medicina Interna e Scienze Mediche
state: Roma
city: Seriate
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Patologia Ostetrica e Ginecologica
state: Roma
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Yonsei University College of Medicine
city: Seoul
country: Korea, Republic of
facility: University of Ulsan College of Medicine
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Amsterdam
country: Netherlands
facility: Netherlands Cancer Institute
state: CX
city: Groningen
country: Netherlands
facility: UMC Groningen Comprehensive Cancer Center
state: GZ
city: Leiden
country: Netherlands
facility: Leiden UMC
state: ZA
city: Auckland
country: New Zealand
facility: New Zealand Clinical Research-Auckland
city: Skórzewo
country: Poland
facility: Centrum Medyczne Pratia Poznan - Skorzewo
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy
city: Pamplona
country: Spain
facility: Universidad de Navarra - Clinica Universidad de Navarra (CUN) - Pamplona
state: Navarra
city: Barcelona
country: Spain
facility: NEXT Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitario Vall dHebron
city: Barcelona
country: Spain
facility: Hospital Duran i Reynals
city: Madrid
country: Spain
facility: Universidad de Navarra - Clinica Universidad de Navarra (CUN) - Madrid
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Basel
country: Switzerland
facility: University Hospital, Basel Switzerland
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois Lausanne
city: Zürich
country: Switzerland
facility: University Hospital of Zurich
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute UK
state: City Of London
city: Oxford
country: United Kingdom
facility: University of Oxford
state: Oxfordshire
city: Glasgow
country: United Kingdom
facility: The Beatson West of Scotland Cancer Centre
state: Scotland
city: Liverpool
country: United Kingdom
facility: University of Liverpool
city: London
country: United Kingdom
facility: University College Hospital London
city: London
country: United Kingdom
facility: Guy's and St Thomas' NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Surrey Quays
country: United Kingdom
facility: Royal Marsden Hospital
Study officials:
References: