IMC-F106C Regimen Versus Nivolumab Regimens in Previously Untreated Advanced Melanoma (PRISM-MEL-301)

Sponsor

Immunocore Ltd (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT06112314

Collaborator

(none)

680

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a phase 3, randomized, controlled study of IMC-F106C plus nivolumab compared to standard nivolumab regimens in HLA-A*02:01-positive participants with previously untreated advanced melanoma.

Condition or Disease	Intervention/Treatment	Phase
Advanced Melanoma	Biological: IMC-F106C Biological: Nivolumab Biological: Nivolumab + Relatlimab	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

680 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 3 Randomized, Controlled Study of IMC-F106C Plus Nivolumab Versus Nivolumab Regimens in HLA-A*02:01-Positive Participants With Previously Untreated Advanced Melanoma (PRISM-MEL-301

Anticipated Study Start Date :

Dec 1, 2023

Anticipated Primary Completion Date :

Dec 1, 2026

Anticipated Study Completion Date :

Dec 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A: IMC-F106C Low Dose + Nivolumab Participants receive IMC-F106C Low Dose once weekly (QW) for the first 12 weeks, then every 2 weeks (Q2W) through Week 51, and then every 4 weeks (Q4W) until Week 101. Nivolumab is given Q4W until Week 101.	Biological: IMC-F106C Soluble PRAME-specific T cell receptor with anti-CD3 scFV concentrate for solution for intravenous (IV) infusion at a unit dose of 0.2 mg/mL. Biological: Nivolumab Concentrate for solution for infusion at a unit dose of 10 mg/mL. Other Names: OPDIVO
Experimental: Arm B: IMC-F106C High Dose + Nivolumab Participants receive IMC-F106C High Dose QW for the first 12 weeks, then Q2W through Week 51, and then Q4W until Week 101. Nivolumab is given Q4W until Week 101.	Biological: IMC-F106C Soluble PRAME-specific T cell receptor with anti-CD3 scFV concentrate for solution for intravenous (IV) infusion at a unit dose of 0.2 mg/mL. Biological: Nivolumab Concentrate for solution for infusion at a unit dose of 10 mg/mL. Other Names: OPDIVO
Active Comparator: Arm C: Nivolumab OR Nivolumab + Relatlimab Participants receive nivolumab 480 mg monotherapy, or nivolumab 480 mg + relatlimab 160 mg, Q4W until Week 101.	Biological: Nivolumab Concentrate for solution for infusion at a unit dose of 10 mg/mL. Other Names: OPDIVO Biological: Nivolumab + Relatlimab Concentrate for solution for infusion at a unit dose of 10 mg/mL. Other Names: OPDUALAG

Arm

Intervention/Treatment

Experimental: Arm A: IMC-F106C Low Dose + Nivolumab

Participants receive IMC-F106C Low Dose once weekly (QW) for the first 12 weeks, then every 2 weeks (Q2W) through Week 51, and then every 4 weeks (Q4W) until Week 101. Nivolumab is given Q4W until Week 101.

Biological: IMC-F106C

Soluble PRAME-specific T cell receptor with anti-CD3 scFV concentrate for solution for intravenous (IV) infusion at a unit dose of 0.2 mg/mL.

Biological: Nivolumab

Concentrate for solution for infusion at a unit dose of 10 mg/mL.

Other Names:

OPDIVO

Experimental: Arm B: IMC-F106C High Dose + Nivolumab

Participants receive IMC-F106C High Dose QW for the first 12 weeks, then Q2W through Week 51, and then Q4W until Week 101. Nivolumab is given Q4W until Week 101.

Biological: IMC-F106C

Soluble PRAME-specific T cell receptor with anti-CD3 scFV concentrate for solution for intravenous (IV) infusion at a unit dose of 0.2 mg/mL.

Biological: Nivolumab

Concentrate for solution for infusion at a unit dose of 10 mg/mL.

Other Names:

OPDIVO

Active Comparator: Arm C: Nivolumab OR Nivolumab + Relatlimab

Participants receive nivolumab 480 mg monotherapy, or nivolumab 480 mg + relatlimab 160 mg, Q4W until Week 101.

Biological: Nivolumab

Concentrate for solution for infusion at a unit dose of 10 mg/mL.

Other Names:

OPDIVO

Biological: Nivolumab + Relatlimab

Concentrate for solution for infusion at a unit dose of 10 mg/mL.

Other Names:

OPDUALAG

Outcome Measures

Primary Outcome Measures

Progression-Free Survival (PFS) [Up to ~24 months]
PFS as assessed by blinded independent central review (BICR) according to Response Evaluation Criteria in Solid Tumours (RECIST 1.1).

Secondary Outcome Measures

Overall Survival (OS) [Up to ~24 months]
OS is the time from randomization to time of death from any cause.
Overall Response Rate (ORR) [Up to ~24 months]
ORR as assessed by BICR according to RECIST 1.1.
Number of Participants Experiencing ≥1 Adverse Event (AE) [Up to ~36 months]
An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign, symptom, or medical condition that occur in the study.
Number of Participants Experiencing ≥1 Serious Adverse Event (SAE) [Up to ~36 months]
An SAE is any untoward medical consequence that results in death; requires inpatient hospitalization or prolongs existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or any other important medical event in the opinion of the Investigator.
Number of Participants Experiencing a Dose Interruption, Reduction, or Discontinuation [Up to ~24 months]
The number of participants with a dose interruption, reduction, or discontinuation due to AE will be reported.
Maximum Plasma Concentration (Cmax) of IMC-F106C [Day 1 of Weeks 1, 2, and 3: Predose and 0.5 and 4 hours postdose]
The Cmax of IMC-F106C will be reported.
Incidence of anti-IMC-F106C Antibodies [Up to ~24 months]
The incidence of anti-IMC-F106C antibodies, including neutralizing antibodies, will be reported.
Association between PFS and Intra-Tumor Immune Cells [Up to ~24 months]
The potential association between the effect of IMC-F106C on efficacy and intra-tumor environment will be explored. Intra-tumor environment is estimated as the ratio of CD3+ to CD163+ cells and the correlation with PFS will be estimated by the hazard ratio (+/- 95% CI) from a Cox model. This analysis will be restricted to subjects randomized to receive IMC-F106C.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Participants must be HLA-A*02:01-positive
Participants must have histologically confirmed Stage IV or unresectable Stage III melanoma
Archived or fresh tumor tissue sample that must be confirmed as adequate
Participants must have measurable disease per RECIST 1.1
Participant must have BRAF V600 mutation status determined
Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
Male and female participants of childbearing potential who are sexually active with a non-sterilized partner must agree to use highly effective methods of birth control from the study screening date until 5 months after the final dose of study intervention

Exclusion Criteria:

Participants with a history of a malignant disease other than those being treated in this study
Participants with untreated, active, or symptomatic central nervous system (CNS) metastases or carcinomatous meningitis
Hypersensitivity to IMC-F106C, nivolumab, relatlimab, or any associated excipients
Participants with clinically significant pulmonary disease or impaired lung function
Participants with clinically significant cardiac disease or impaired cardiac function
Participants with active autoimmune disease requiring immunosuppressive treatment
Participants with any medical condition that is poorly controlled or that would, in the Investigator's or Sponsor's judgment, adversely impact the participant's participation in the clinical study due to safety concerns, compliance with clinical study procedures, or interpretation of study results
Participants who received prior systemic anticancer therapy for unresectable or metastatic melanoma
Participants with a history of a life-threatening AE related to prior anti-PD-(L)1 or anti-LAG-3

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California San Diego (UCSD) - Moores Cancer Center	La Jolla	California	United States	92093
2	The Angeles Clinic and Research Institute - West Los Angeles - The Melanoma Center	Los Angeles	California	United States	90025
3	UCSF Medical Center - Helen Diller Family Comprehensive Cancer Center	San Francisco	California	United States	94143
4	UCLA Department of Medicine- Hematology/Oncology	Westwood	California	United States	90024
5	University of Colorado Hospital (UCH) - Medical Campus	Aurora	Colorado	United States	80045
6	Georgetown University Medical Center (GUMC)	Washington	District of Columbia	United States	20007-2113
7	Moffitt Cancer Center - Magnolia Campus	Tampa	Florida	United States	33612
8	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
9	Columbia University - Herbert Irving Comprehensive Cancer Center	New York	New York	United States	10032
10	Providence Portland Medical Center	Portland	Oregon	United States	97213-2933
11	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
12	Tennessee Oncology	Nashville	Tennessee	United States	37203
13	Instituto Alexander Fleming	Buenos Aires		Argentina
14	University of Sydney - Melanoma Institute Australia (MIA) - The Poche Centre	Wollstonecraft		Australia
15	The University of Queensland (UQ) - Princess Alexandra Hospital (PAH)	Woolloongabba		Australia
16	Universitätsklinikum St. Pölten	St. Poelten		Austria
17	Cliniques Universitaires Saint-Luc, Medical Oncology	Brussels		Belgium
18	Universitair Ziekenhuis Brussel	Brussels		Belgium
19	Universitaire Ziekenhuizen (UZ) Leuven - General Medical Oncology	Leuven		Belgium
20	Oncosite	Ijuí		Brazil
21	Instituto Américas - Instituto de Educação Pesquisa e Gestão em Saúde Oncosite	Rio de Janeiro		Brazil
22	Instituto Nacional de Cancer (INCA) (Brazilian National Cancer Institute)	Rio De Janeiro		Brazil
23	University of Alberta - Cross Cancer Institute	Edmonton		Canada
24	UHN - Princess Margaret Cancer Centre, University Health Network	Toronto		Canada
25	Centre Hospitalier Universitaire (CHU) de Bordeaux - Hospitalier Saint-Andre	Bordeaux		France
26	Assistance Publique-Hôpitaux de Paris (AP-HP)	Boulogne-Billancourt		France
27	Assistance Publique Hôpitaux de Marseille - Hôpital de la Timone	Marseille		France
28	Assistance Publique - Hôpitaux de Paris - Hôpital Saint-Louis - Centre d'Onco-Dermatologie	Paris		France
29	Institut Claudius Regaud - Institut Universitaire du Cancer de Toulouse-Oncopole (IUCT-Oncopole)	Toulouse		France
30	Institut de Cancerologie Gustave-Roussy	Villejuif		France
31	Charite-Universitaetsmedizin Berlin - Campus Charite Mitte (CCM) - Klinik fuer Dermatologie Venerologie und Allergologie - Hauttumorcentrum Charite (HTCC)	Berlin		Germany
32	Technische Universitaet Dresden - Universitaetsklinikum Carl Gustav Carus	Dresden		Germany
33	Universitaetsklinikum Essen - Klinik und Poliklinik fuer Dermatologie, Venerologie und Allergologie	Essen		Germany
34	University Medical Center Hamburg-Eppendorf (UKE)	Hamburg		Germany
35	Universitaetsklinikum Heidelberg (UKHD) - Hautklinik	Heidelberg		Germany
36	Universitaetsklinikum Leipzig	Leipzig		Germany
37	Johannes Wesling Medical Center	Minden		Germany
38	Fondazione IRCCS - Istituto Nazionale dei Tumori - Milano	Milano		Italy
39	Istituto Nazionale Tumori IRCCS Fondazione "G. Pascale"	Napoli		Italy
40	Azienda Ospedaliera Universitaria Senese - Istituto Toscano Tumori (ITT) - Siena	Siena		Italy
41	Hospital Hispano Investigacion Clinica	Guadalajara		Mexico
42	Klinika Nowotworów Tkanek Miękkich, Kości i Czerniaków Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy	Warszawa		Poland
43	Institutul Oncologic " Prof. Dr. Ion Chiricuta" Str. (IOCN)	Cluj-Napoca		Romania
44	Sf Nectarie Oncology Center, Oncology Department	Craiova		Romania
45	Hospital Clinic de Barcelona	Barcelona		Spain
46	Hospital Universitari Vall d'Hebron	Barcelona		Spain
47	Institut Català d'Oncologia (ICO) - Hospital Duran i Reynals	Barcelona		Spain
48	Instituto Oncologico Dr. Rosell (IOR) Hospital Universitario Dexeus	Barcelona		Spain
49	Hospital General Universitario Gregorio Marañon (HGUGM)	Madrid		Spain
50	Hospital Universitario La Paz (HULP)	Madrid		Spain
51	Hospital Universitario Ramon y Cajal	Madrid		Spain
52	Hospital Civil (Hospital Regional Universitario de Malaga)	Malaga		Spain
53	Hospital Universitario Virgen Macarena	Sevilla		Spain
54	Hospital Clinico Universitario de Valencia	Valencia		Spain
55	UniversitaetsSpital Zuerich - Dermatologische Klinik	Zürich		Switzerland
56	Cambridge University Hospitals NHS Foundation Trust - Addenbrooke's Hospital (AH) - Oncology Centre	Cambridge		United Kingdom
57	Beatson West of Scotland Cancer Centre	Glasgow		United Kingdom
58	The Clatterbridge Cancer Centre (CCC) NHS Foundation Trust (Clatterbridge Centre for Oncology NHS Foundation Trust) - Clatterbridge Cancer Centre - Aintree	Liverpool		United Kingdom
59	The Royal Marsden NHS Foundation Trust - Royal Marsden Hospital (RMH) - London	London		United Kingdom
60	The Christie NHS Foundation Trust - The Christie Clinic	Manchester		United Kingdom
61	East and North Hertfordshire NHS Trust - Mount Vernon Hospital - Mount Vernon Cancer Centre (MVCC)	Northwood		United Kingdom
62	Oxford University Hospitals NHS Trust - Churchill Hospital	Oxford		United Kingdom

Sponsors and Collaborators

Immunocore Ltd

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Immunocore Ltd

ClinicalTrials.gov Identifier:

NCT06112314

Other Study ID Numbers:

IMC-F106C-301
2023-505306-42-00

First Posted:

Nov 1, 2023

Last Update Posted:

Nov 1, 2023

Last Verified:

Oct 1, 2023

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Additional relevant MeSH terms:

Melanoma

Nivolumab

Relatlimab

Study Results

No Results Posted as of Nov 1, 2023