TriangleNCT03070392 · CITED IN SOURCE DOCUMENTS
Safety and Efficacy of IMCgp100 Versus Investigator Choice in Advanced Uveal Melanoma
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE2
- Status at capture
- COMPLETED
- Registry last update
- 2026-03-17
To evaluate the overall survival of HLA-A\*0201 positive adult patients with previously untreated advanced UM receiving IMCgp100 compared to Investigator's Choice of dacarbazine, ipilimumab, or pembrolizumab.
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What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Efficacy: Overall Survival
Safety: Number of Participants With Treatment Emergent Adverse Events
Efficacy: Progression Free Survival (PFS)
Quality-of-Life: Change From Baseline in EQ-5D,5L Domain Scores
Quality-of-life: Change From Baseline in EQ-5D Visual Analogue Score (VAS)
Quality-of-Life: Change From Baseline in EORTC QLQ-C30 Global Health Status
Pharmacokinetics (PK): Tebentafusp Concentration
Efficacy: Objective Response Rate (ORR)
Efficacy: Duration of Response (DOR)
Efficacy: Disease Control Rate (DCR)
Pharmacokinetics: Frequency of Anti-IMCgp100 Antibody Formation
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- Inclusion Criteria 1. Male or female participants age ≥ 18 years of age at the time of informed consent 2. Ability to provide and understand written informed consent prior to any study procedures 3. Histologically or cytologically confirmed metastatic UM 4. Must meet the following criteria related to prior treatment: * No prior systemic therapy in the metastatic or advanced setting including chemotherapy, immunotherapy, or targeted therapy * No prior regional, liver-directed therapy including chemotherapy, radiotherapy, or embolization * Prior surgical resection of oligometastatic disease is allowed * Prior neoadjuvant or adjuvant therapy is allowed provided administered in the curative setting in participants with localized disease. Participants may not be re-treated with an Investigator's Choice therapy that was administered as adjuvant or neoadjuvant treatment. Additionally, participants who have received nivolumab as prior adjuvant/neoadjuvant treatment should not receive pembrolizumab as Investigator's Choice therapy. 5. HLA A\*0201 positive by central assay 6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 at Screening 7. Participants have measurable disease or non-measurable disease according to RECIST v1.1 8. All other relevant medical conditions must be well-managed and stable, in the opinion of the investigator, for at least 28 days prior to first administration of study drug Exclusion Criteria 1. Out-of-range laboratory values 2. History of severe hypersensitivity reactions (eg, anaphylaxis) to other biologic drugs or monoclonal antibodies 3. Clinically significant cardiac disease or impaired cardiac function, 4. Presence of symptomatic or untreated central nervous system (CNS) metastases, or CNS metastases that require doses of corticosteroids within the prior 3 weeks to study Day 1. Participants with brain metastases are eligible if lesions have been treated with localized therapy and there is no evidence of PD for at least 4 weeks by magnetic resonance imaging (MRI) prior to the first dose of study drug 5. Active infection requiring systemic antibiotic therapy. Participants requiring systemic antibiotics for infection must have completed therapy at least 1 week prior to the first dose of study drug 6. Known history of human immunodeficiency virus infection (HIV). Testing for HIV status is not necessary unless clinically indicated 7. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection per institutional protocol. Testing for HBV or HCV status is not necessary unless clinically indicated or the patient has a history of HBV or HCV infection 8. Malignant disease, other than that being treated in this study. Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 2 years prior to study treatment; completely resected basal cell and squamous cell skin cancers; any malignancy considered to be indolent and that has never required therapy; and completely resected carcinoma in situ of any type 9. Any medical condition that would, in the investigator's or Sponsor's judgment, prevent the participants participation in the clinical study due to safety concerns, compliance with clinical study procedures or interpretation of study results 10. Participants receiving systemic steroid therapy or any other systemic immunosuppressive medication at any dose level, as these may interfere with the mechanism of action of study treatment. Local steroid therapies (eg, otic, ophthalmic, intra-articular, or inhaled medications) are acceptable 11. History of adrenal insufficiency 12. History of interstitial lung disease 13. History of pneumonitis that required corticosteroid treatment or current pneumonitis 14. History of colitis or inflammatory bowel disease 15. Major surgery within 2 weeks of the first dose of study drug (minimally invasive procedures such as bronchoscopy, tumor biopsy, insertion of a central venous access device, and insertion of a feeding tube are not considered major surgery and are not exclusionary) 16. Radiotherapy within 2 weeks of the first dose of study drug, with the exception of palliative radiotherapy to a limited field, such as for the treatment of bone pain or a focally painful tumor mass 17. Use of hematopoietic colony-stimulating growth factors (e.g., G-CSF, GM-CSF, M-CSF) ≤ 2 weeks prior to start of study drug. An erythroid-stimulating agent is allowed as long as it was initiated at least 2 weeks prior to the first dose of study treatment and the patient is not red blood cell transfusion dependent 18. Pregnant, likely to become pregnant, or lactating women (where pregnancy is defined as the state of a female after conception and until the termination of gestation) 19. Women of childbearing potential who are sexually active with a non-sterilized male partner, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective contraception during study treatment (defined in Section 6.7), and must agree to continue using such precautions for 6 months after the final dose of investigational product; cessation of birth control after this point should be discussed with a responsible physician. Highly effective methods of contraception are described in Section 6.7 20. Male participants must be surgically sterile or use double barrier contraception methods from enrollment through treatment and for 6 months following administration of the last dose of study drug 21. Participant who are in an institution due to official or judicial order. 22. Participant who are the investigator or any subinvestigator, research assistant, pharmacist, study coordinator, or other staff thereof, directly involved in the conduct of the study. 23. Contraindication for treatment with Investigator's Choice alternatives (dacarbazine, ipilimumab and pembrolizumab) as per applicable labelling. Participant may have a contraindication to 1 or 2 of the choices if he/she is a candidate for dosing with at least 1 Investigator's Choice and meets all other study eligibility criteria.
- healthy Volunteers
- false
- maximum Age
- 99 Years
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Biologic:IMCgp100 (Soluble gp 100-specific T cell receptor with anti - CD3 scFV: IMCgp100)
- intervention Names
- Biological: IMCgp100
- label
- IMCgp100 (tebentafusp, Kimmtrak)
- type
- EXPERIMENTAL
- description
- 1 of 3 Investigator's Choice options: Systemic Dacarbazine 1 of 3 Investigator's Choice options: Systemic Ipilimumab 1 of 3 Investigator's Choice options: Systemic Pembrolizumab
- intervention Names
- Drug: Dacarbazine
- Biological: Ipilimumab
- Biological: Pembrolizumab
- label
- Investigator's Choice
- type
- ACTIVE_COMPARATOR
- interventions
- arm Group Labels
- IMCgp100 (tebentafusp, Kimmtrak)
- description
- IMCgp100 is to be administered at 20 mcg cycle 1 day1, then 30 mcg cycle 1 day 8, then 68 mcg cycle 1 day 15 and weekly thereafter by IV infusion over 15 minutes until confirmed disease progression or unacceptable toxicity
- name
- IMCgp100
- type
- BIOLOGICAL
- arm Group Labels
- Investigator's Choice
- description
- Dacarbazine is to be administered at 1,000 mg/m2 of body surface area IV infusion every 3 weeks until disease progression or unacceptable toxicity
- name
- Dacarbazine
- other Names
- DTIC-Dome
- DTIC
- DIC
- Imidazole Carboxamide
- type
- DRUG
- arm Group Labels
- Investigator's Choice
- description
- Ipilimumab is to be administered at 3 mg/kg IV infusion over 90 minutes every 3 weeks for a total of 4 treatments
- name
- Ipilimumab
- other Names
- Yervoy
- type
- BIOLOGICAL
- arm Group Labels
- Investigator's Choice
- description
- Pembrolizumab is to be administered at 2 mg/kg IV infusion up to a maximum of 200 mg administered Intravenously over 30 minutes every 3 weeks or 200 mg fixed dose administered intravenously every 3 weeks where approved locally until confirmed disease progression or unacceptable toxicity
- name
- Pembrolizumab
- other Names
- Keytruda
- type
- BIOLOGICAL
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 378
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- Overall survival is defined as the time from randomization to date of death due to any cause.
- measure
- Efficacy: Overall Survival
- time Frame
- From randomization to the data cut off date of 13-Oct-2020; median follow-up duration was 14.1 months.
- secondary Outcomes
- description
- Safety was defined as the number of participants with treatment emergent adverse events, including laboratory abnormalities, ECG changes, and/or physical examination findings.
- measure
- Safety: Number of Participants With Treatment Emergent Adverse Events
- time Frame
- Safety was assessed from informed consent through 90 days after end of treatment, up to 36 months.
- description
- Progression free survival (PFS) is defined as the time from randomization to the date of progression (RECIST v1.1) or death due to any cause.
- measure
- Efficacy: Progression Free Survival (PFS)
- time Frame
- PFS was assessed every 3 months from randomization until disease progression or death, up to 36 months.
- description
- General health status was assessed using the EQ-5D,5L questionnaire, which includes five dimensions (5D): mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 3 scoring levels, where 1 indicates a better health state (no problems) and 3 indicates a worse health state. A positive change indicates improvement.
- measure
- Quality-of-Life: Change From Baseline in EQ-5D,5L Domain Scores
- time Frame
- EQ-5D,5L was assessed at baseline (Cycle 1 Day 1) and on Day 1 of every other cycle to Cycle 5 Day 1, every fourth cycle thereafter, beginning with Cycle 9 Day 1 and End of Treatment (EOT), up to 36 months. Each cycle is 21 days.
- description
- The EQ-5D VAS score records the participant's self-rated health on a vertical visual analogue scale, with 0 being the worst imaginable health state and 100 being the best imaginable health state. A positive change indicates improvement.
- measure
- Quality-of-life: Change From Baseline in EQ-5D Visual Analogue Score (VAS)
- time Frame
- EQ-5D,5L VAS was assessed at baseline (Cycle 1 Day 1) and on Day 1 of every other cycle to Cycle 5 Day 1, every fourth cycle thereafter, beginning with Cycle 9 Day 1 and End of Treatment (EOT), up to 36 months. Each cycle is 21 days.
- description
- Global health status and quality of life was assessed using the EORTC QLQ-C30 questionnaire. The score range for the EORTC QLQ-C30 is from 0 to 100, with higher scores indicating better functioning and better global health status and health-related quality of life. A positive change indicates improvement.
- measure
- Quality-of-Life: Change From Baseline in EORTC QLQ-C30 Global Health Status
- time Frame
- EORTC QLQ-C30 was assessed at baseline (Cycle 1 Day 1) and on Day 1 of every other cycle to Cycle 5 Day 1, every fourth cycle thereafter, beginning with Cycle 9 Day 1 and End of Treatment (EOT), up to 36 months. Each cycle is 21 days.
- description
- Serum PK concentrations of tebentafusp were collected over time.
- measure
- Pharmacokinetics (PK): Tebentafusp Concentration
- time Frame
- PK concentrations were assessed at pre-dose, end of infusion and anytime in the 12 to 24 hour window after completion of the infusion in Cycle 1 on Days 1, 8 and 15.
- description
- Objective response rate (ORR) is defined as the proportion of patients achieving an objective response (RECIST v1.1).
- measure
- Efficacy: Objective Response Rate (ORR)
- time Frame
- ORR will be assessed after every participant has had at least 3 assessments, conducted every 3 months, up to 5.5 years.
- description
- Duration of response (DOR) is defined as the time from first documented objective response (RECIST v1.1) until the date of documented disease progression.
- measure
- Efficacy: Duration of Response (DOR)
- time Frame
- DOR will be assessed every 3 months from randomization until disease progression, assessed up to 5.5 years.
- description
- Disease control rate (DCR) is defined as the proportion of patients with either an objective response or stable disease (RECIST v1.1)
- measure
- Efficacy: Disease Control Rate (DCR)
- time Frame
- DCR will be assessed every 3 months from randomization until disease progression, up to 5.5 years.
- measure
- Pharmacokinetics: Frequency of Anti-IMCgp100 Antibody Formation
- time Frame
- Approximately 5 assessments will be performed between first dose of IMCgp100 and end of treatment, assessed up to 5.5 years.
Full study description
- brief Summary
- To evaluate the overall survival of HLA-A\*0201 positive adult patients with previously untreated advanced UM receiving IMCgp100 compared to Investigator's Choice of dacarbazine, ipilimumab, or pembrolizumab.
- detailed Description
- This Phase II study is designed to evaluate the safety and efficacy of IMCgp100 compared with Investigator's Choice (dacarbazine, ipilimumab or pembrolizumab) in HLA-A\*0201 positive adult patients with advanced UM treated in the first line setting with no prior systemic or liver-directed chemo-, radio- or immune-therapy administered in the advanced setting (prior surgical resection of liver metastases and adjuvant systemic therapy are acceptable). Comparison of the IMCgp100 efficacy results in this Phase II study will be made with the concurrently randomized arm (Investigator's Choice) with a primary endpoint of overall survival (OS) and secondary efficacy endpoints of progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), and disease control rate (DCR).
Source references
- references
- citation
- Piperno-Neumann S, Rutkowski P, Hassel JC, Butler MO, Schlaak M, Sullivan RJ, Dummer R, Kirkwood JM, Sacco JJ, Shoushtari AN, Piulats JM, Salama AKS, Orloff MM, Joshua AM, Ochsenreither S, Gastaud L, Curti BD, Demidov LV, Milhem MM, Chmielowski B, Kendra KL, Ascierto PA, Bernicker EH, Carvajal RD, Collins L, Lockwood S, Patel JM, Hamid OA, Baurain JF, Nathan PD. Five-year survival with tebentafusp in metastatic uveal melanoma. Ann Oncol. 2026 May 19:S0923-7534(26)00879-3. doi: 10.1016/j.annonc.2026.05.695. Online ahead of print.
- pmid
- 42162665
- type
- DERIVED
- citation
- Hassel JC, Piperno-Neumann S, Rutkowski P, Baurain JF, Schlaak M, Butler MO, Sullivan RJ, Dummer R, Kirkwood JM, Orloff M, Sacco JJ, Ochsenreither S, Joshua AM, Gastaud L, Curti B, Piulats JM, Salama AKS, Shoushtari AN, Demidov L, Milhem M, Chmielowski B, Kim KB, Carvajal RD, Hamid O, Collins L, Ranade K, Holland C, Pfeiffer C, Nathan P. Three-Year Overall Survival with Tebentafusp in Metastatic Uveal Melanoma. N Engl J Med. 2023 Dec 14;389(24):2256-2266. doi: 10.1056/NEJMoa2304753. Epub 2023 Oct 21.
- pmid
- 37870955
- type
- DERIVED
- citation
- Nathan P, Hassel JC, Rutkowski P, Baurain JF, Butler MO, Schlaak M, Sullivan RJ, Ochsenreither S, Dummer R, Kirkwood JM, Joshua AM, Sacco JJ, Shoushtari AN, Orloff M, Piulats JM, Milhem M, Salama AKS, Curti B, Demidov L, Gastaud L, Mauch C, Yushak M, Carvajal RD, Hamid O, Abdullah SE, Holland C, Goodall H, Piperno-Neumann S; IMCgp100-202 Investigators. Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma. N Engl J Med. 2021 Sep 23;385(13):1196-1206. doi: 10.1056/NEJMoa2103485.
- pmid
- 34551229
- type
- DERIVED
Source notices and limitations
Discovery and provenance
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- CLINICAL STUDIES Study IMCgp100-202: First line metastatic uveal melanoma KIMMTRAK was evaluated in IMCgp100-202, a randomized, open-label, multicenter trial (NCT03070392) that enrolled patients with metastatic uveal melanoma (N=378). Patients were required to be HLA-A*02:01 genotype positive identified by a central assay. Patie
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Preserved source evidence · Not medical advice