NCT02570308

A Study of the Intra-Patient Escalation Dosing Regimen With IMCgp100 in Patients With Advanced Uveal Melanoma

Completed Phase 1, PHASE2 Results posted Last updated 21 March 2023

What this trial tests

Phase 1, PHASE2 trial testing IMCgp100 in Uveal Melanoma in 146 participants. Completed in 17 October 2022.

Timeline

29 February 2016

Primary endpoint
20 March 2020

17 October 2022

Quick facts

Lead sponsor	Immunocore Ltd
Phase	Phase 1, PHASE2
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	146
Start date	29 February 2016
Primary completion	20 March 2020
Estimated completion	17 October 2022
Sites	26 locations across United Kingdom, Germany, Canada, United States, Spain

Drugs / interventions tested

• IMCgp100

Conditions studied

• Uveal Melanoma — all drugs for Uveal Melanoma →

Sponsor

Immunocore Ltd — full company profile →

Who can join

18 and older, any sex, with Uveal Melanoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With a Dose Limiting Toxicity (DLT) in Phase 1 Primary · Up to 49 months

Number of participants with a dose limiting toxicity, defined as an adverse event (AE) or abnormal laboratory value assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle of treatment and meets any of the pre-specified criteria.

Group	Value	95% CI
Phase 1 Dose Escalation Cohort 1: 54 mcg Tebentafusp	0
Phase 1 Dose Escalation Cohort 2: 64 mcg Tebentafusp	1
Phase 1 Dose Escalation Cohort 3: 73 mcg Tebentafusp	2
Phase 1 Dose Escalation Cohort 4: 68 mcg Tebentafusp	0

Objective Response Rate in Phase 2 Primary · Up to 38 months

Objective response rate (ORR) is defined as the percentage of participants with measurable disease with at least 1 visit response of complete response (CR) or partial response (PR) that is confirmed at least 4 weeks later, as defined in RECIST v.1.1 and assessed by an independent central review (ICR). The denominator in the calculation of the ORR is the number of participants in the full analysis set with measurable disease at baseline.

Group	Value	95% CI
Phase 2 Dose Expansion: 68 mcg Tebentafusp	4.7	1.8 – 10.0

Objective Response Rate in Phase 1 Secondary · Up to 49 months

ORR is defined as the percentage of participants with measurable disease with at least 1 visit response of CR or PR that is confirmed at least 4 weeks later, as defined in RECIST v.1.1 and assessed by an investigator. The denominator in the calculation of the ORR is the number of participants in the full analysis set with measurable disease at baseline.

Group	Value	95% CI
Phase 1 Dose Escalation	15.8	3.4 – 39.6

Progression-free Survival Secondary · Up to 49 months

Progression-free survival is defined as the time in months from first dose of study drug until the date of disease progression or death (by any cause in the absence of disease progression) as assessed by RECIST v1.1 by the investigator for Phase 1 and ICR for Phase 2.

Group	Value	95% CI
Phase 1 Dose Escalation	7.4	1.2 – 14.8
Phase 2 Dose Expansion	2.8	2.0 – 3.7

Disease Control Rate Secondary · 24 weeks

Disease control rate (DCR) is defined as the percentage of participants with a best overall response of CR or PR or stable disease (SD) recorded at least 24 weeks (± 1 week) after commencement of study drug and prior to any progressive disease (PD) event, as assessed by RECIST v1.1 by the investigator for Phase 1 and ICR for Phase 2.

Group	Value	95% CI
Phase 1 Dose Escalation	47.4	24.4 – 71.1
Phase 2 Dose Expansion	22.8	15.9 – 31.1

Duration of Response Secondary · Up to 49 months

Duration of response (DOR) is defined as the time in months from the date of first documented objective response (CR or PR) until the date of documented disease progression or death by any cause in the absence of disease progression as assessed by RECIST v1.1 by the investigator for Phase 1 and ICR for Phase 2.

Group	Value	95% CI
Phase 1 Dose Escalation	7.425	3.713 – NA
Phase 2 Dose Expansion	8.706	5.552 – 24.542

Time to Response Secondary · Up to 49 months

Time to response (TTR) is defined as the time in months from the date of first dose of study drug until the date of first documented objective response as assessed by RECIST v1.1 by the investigator for Phase 1 and ICR for Phase 2.

Group	Value	95% CI
Phase 1 Dose Escalation	5.5	± 1.8
Phase 2 Dose Expansion	7.0	± 6.9

Overall Survival Secondary · Up to 49 months

Overall survival (OS) is defined as the time in months from the date of first dose of study drug until death due to any cause in general.

Group	Value	95% CI
Phase 1 Dose Escalation	29.6	10.9 – 42.2
Phase 2 Dose Expansion	16.8	12.9 – 21.3

Minor Response Rate Secondary · Up to 49 months

Rate of minor response (or better) is defined as the proportion of participants with a confirmed CR, PR, or minor response (MinR) as assessed by RECIST v1.1 by the investigator for Phase 1 or ICR for Phase 2, where MinR is a reduction from baseline in sum of diameters between 10%-29%. The sum of diameters is defined as per RECIST v1.1 as the sum of longest diameters or short axis of target lesions (mm).

Group	Value	95% CI
Phase 1 Dose Escalation	26.3	9.1 – 51.2
Phase 2 Dose Expansion	11.0	6.2 – 17.8

Number of Participants With Treatment Dose Interruptions or Reductions Secondary · Up to 49 months

Tolerability of study treatment was assessed by summarizing the number of participants with dose interruptions or reductions that occurred during the treatment period.

Group	Value	95% CI
Phase 1 Dose Escalation Cohort 1: 54 mcg Tebentafusp	2
Phase 1 Dose Escalation Cohort 2: 64 mcg Tebentafusp	4
Phase 1 Dose Escalation Cohort 2: 73 mcg Tebentafusp	3
Phase 1 Dose Escalation Cohort 2: 68 mcg Tebentafusp	4
Phase 2 Dose Expansion	49

Area Under the Plasma Concentration-Time Curve (AUC) of Tebentafusp Secondary · Cycle 1 Day 1 and Cycle 1 Day 15: predose, end of infusion, and 4 and 8 hours postdose

The AUC was determined in in dose escalation cohorts.

Cycle 1 Day 1

Group	Value	95% CI
Phase 1 Dose Escalation Cohort 1: 54 mcg Tebentafusp	28550	± 27.0
Phase 1 Dose Escalation Cohort 2: 64 mcg Tebentafusp	36530	± 23.3
Phase 1 Dose Escalation Cohort 3: 73 mcg Tebentafusp	32920	± 18.2
Phase 1 Dose Escalation Cohort 4: 68 mcg Tebentafusp	33030	± 16.5

Cycle 1 Day 15

Group	Value	95% CI
Phase 1 Dose Escalation Cohort 1: 54 mcg Tebentafusp	81310	± 33.7
Phase 1 Dose Escalation Cohort 2: 64 mcg Tebentafusp	98660	± 34.8
Phase 1 Dose Escalation Cohort 3: 73 mcg Tebentafusp	106800	± 11.6
Phase 1 Dose Escalation Cohort 4: 68 mcg Tebentafusp	109800	± 23.3

Maximum Plasma Concentration (Cmax) of Tebentafusp Secondary · Cycle 1 Day 1 and Cycle 1 Day 15: predose, end of infusion, and 4 and 8 hours postdose

The Cmax is determined in dose escalation cohorts.

Cycle 1 Day 1

Group	Value	95% CI
Phase 1 Dose Escalation Cohort 1: 54 mcg Tebentafusp	3050	± 15.1
Phase 1 Dose Escalation Cohort 2: 64 mcg Tebentafusp	3294	± 22.7
Phase 1 Dose Escalation Cohort 3: 73 mcg Tebentafusp	3041	± 21.7
Phase 1 Dose Escalation Cohort 4: 68 mcg Tebentafusp	3640	± 23.3

Cycle 1 Day 15

Group	Value	95% CI
Phase 1 Dose Escalation Cohort 1: 54 mcg Tebentafusp	8885	± 17.2
Phase 1 Dose Escalation Cohort 2: 64 mcg Tebentafusp	9523	± 23.0
Phase 1 Dose Escalation Cohort 3: 73 mcg Tebentafusp	11300	± 11.7
Phase 1 Dose Escalation Cohort 4: 68 mcg Tebentafusp	11520	± 25.8

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 49 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Phase 1 Dose Escalation Cohort 1: 54 mcg Tebentafusp

Serious: 2/3 (67%)

Deaths: 1/3

Phase 1 Dose Escalation Cohort 2: 64 mcg Tebentafusp

Serious: 2/6 (33%)

Deaths: 5/6

Phase 1 Dose Escalation Cohort 3: 73 mcg Tebentafusp

Serious: 3/4 (75%)

Deaths: 4/4

Phase 1 Dose Escalation Cohort 4: 68 mcg Tebentafusp

Serious: 3/6 (50%)

Deaths: 4/6

Phase 2 Dose Expansion: 68 mcg Tebentafusp

Serious: 42/127 (33%)

Deaths: 69/127

Serious adverse events (54 terms)

Reaction	System	Phase 1 Dose Escalation Co…	Phase 1 Dose Escalation Co…	Phase 1 Dose Escalation Co…	Phase 1 Dose Escalation Co…	Phase 2 Dose Expansion: 68…
Pyrexia	General disorders	—	—	—	—	—
Cytokine release syndrome	Immune system disorders	—	—	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—	—	—
Sepsis	Infections and infestations	—	—	—	—	—
Rash maculo-papular	Skin and subcutaneous tissue disorders	—	—	—	—	—
Hypotension	Vascular disorders	—	—	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—
Atrial flutter	Cardiac disorders	—	—	—	—	—
Diarrhea	Gastrointestinal disorders	—	—	—	—	—
Sinus tachycardia	Cardiac disorders	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—
Gamma-glutamyltransferase increased	Investigations	—	—	—	—	—
Hypophosphatemia	Metabolism and nutrition disorders	—	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Tumor pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—
Spinal cord compression	Nervous system disorders	—	—	—	—	—
Pleural effusion	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Hyperbilirubinemia	Hepatobiliary disorders	—	—	—	—	—
Infusion-related reaction	Injury, poisoning and procedural complications	—	—	—	—	—
Bone pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Hypoxia	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Hypotension	Vascular disorders	—	—	—	—	—
Atrial fibrillation	Cardiac disorders	—	—	—	—	—
Cardiac failure	Cardiac disorders	—	—	—	—	—

Other adverse events (215 terms — click to expand)

Reaction	System	Phase 1 Dose Escalation Co…	Phase 1 Dose Escalation Co…	Phase 1 Dose Escalation Co…	Phase 1 Dose Escalation Co…	Phase 2 Dose Expansion: 68…
Pyrexia	General disorders	—	—	—	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—
Chills	General disorders	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—
Hypotension	Vascular disorders	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—
Dry skin	Skin and subcutaneous tissue disorders	—	—	—	—	—
Rash maculo-papular	Skin and subcutaneous tissue disorders	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—
Edema peripheral	General disorders	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Periorbital edema	Eye disorders	—	—	—	—	—
Hair color changes	Skin and subcutaneous tissue disorders	—	—	—	—	—
Diarrhea	Gastrointestinal disorders	—	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—
Rash generalized	Skin and subcutaneous tissue disorders	—	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Skin exfoliation	Skin and subcutaneous tissue disorders	—	—	—	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—	—	—	—
Skin hypopigmentation	Skin and subcutaneous tissue disorders	—	—	—	—	—
Dyspnea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Influenza like illness	General disorders	—	—	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Erythema	Skin and subcutaneous tissue disorders	—	—	—	—	—
Pruritus generalized	Skin and subcutaneous tissue disorders	—	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—	—
Skin hyperpigmentation	Skin and subcutaneous tissue disorders	—	—	—	—	—
Weight decreased	Investigations	—	—	—	—	—
Insomnia	Psychiatric disorders	—	—	—	—	—
Generalized erythema	Skin and subcutaneous tissue disorders	—	—	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Hypertension	Vascular disorders	—	—	—	—	—
Anemia	Blood and lymphatic system disorders	—	—	—	—	—

Most-reported serious reactions: Pyrexia, Cytokine release syndrome, Alanine aminotransferase increased, Sepsis, Rash maculo-papular, Hypotension, Aspartate aminotransferase increased, Abdominal pain.

Data from ClinicalTrials.gov NCT02570308 adverse events section.

Sponsor's own description

IMCgp100-102 is a Phase I/II study of the weekly intra-patient escalation dose regimen with IMCgp100 as a single agent in participants with metastatic uveal melanoma (mUM). According to this regimen, all participants in the trial received 2 weekly doses of IMCgp100 at a dose level below the identified weekly recommended Phase II dose (RP2D-QW) and then a dose escalation commenced at the third weekly dose at C1D15. The Phase I testing of the intra-patient escalation dosing regimen is designed to achieve a higher exposure and maximal plasma concentration of IMCgp100 after doses at Cycle 1 Day 15 (C1D15) and thereafter.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Uveal melanoma: epidemiology, etiology, and treatment of primary disease.
   Krantz BA, Dave N, Komatsubara KM, Marr BP, et al · · 2017 · cited 270× · PMID 28203054 · DOI 10.2147/opth.s89591
2. Treatment of uveal melanoma: where are we now?
   Yang J, Manson DK, Marr BP, Carvajal RD. · · 2018 · cited 229× · PMID 29497459 · DOI 10.1177/1758834018757175
3. Bispecific antibodies and their applications.
   Fan G, Wang Z, Hao M, Li J. · · 2015 · cited 200× · PMID 26692321 · DOI 10.1186/s13045-015-0227-0
4. Clinical and molecular response to tebentafusp in previously treated patients with metastatic uveal melanoma: a phase 2 trial.
   Carvajal RD, Butler MO, Shoushtari AN, Hassel JC, et al · · 2022 · cited 123× · PMID 36229663 · DOI 10.1038/s41591-022-02015-7
5. Overcoming Challenges for CD3-Bispecific Antibody Therapy in Solid Tumors.
   Middelburg J, Kemper K, Engelberts P, Labrijn AF, et al · · 2021 · cited 122× · PMID 33466732 · DOI 10.3390/cancers13020287
6. Overcoming the challenges associated with CD3+ T-cell redirection in cancer.
   Singh A, Dees S, Grewal IS. · · 2021 · cited 82× · PMID 33469153 · DOI 10.1038/s41416-020-01225-5
7. Biology drives the discovery of bispecific antibodies as innovative therapeutics.
   Nie S, Wang Z, Moscoso-Castro M, D'Souza P, et al · · 2020 · cited 79× · PMID 33928225 · DOI 10.1093/abt/tbaa003
8. Circulating tumor DNA to monitor treatment response in solid tumors and advance precision oncology.
   Bartolomucci A, Nobrega M, Ferrier T, Dickinson K, et al · · 2025 · cited 72× · PMID 40122951 · DOI 10.1038/s41698-025-00876-y