Safety and Efficacy of IMCgp100 Versus Investigator Choice in Advanced Uveal Melanoma

• Sponsor: Immunocore Ltd (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03070392
• Collaborator: (none)
• Enrollment: 378
• Locations: 56
• Arms: 2
• Anticipated Duration (Months): 64.5
• Patients Per Site: 6.8
• Patients Per Site Per Month: 0.1

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Uveal Melanoma	Biological: IMCgp100; Drug: Dacarbazine; Biological: Ipilimumab; Biological: Pembrolizumab	Phase 2

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).

Study Design

• Study Type: Interventional
• Actual Enrollment: 378 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Randomized, Open-label, Multi-center Study of the Safety and Efficacy of IMCgp100 Compared With Investigator Choice in HLA-A*0201 Positive Patients With Previously Untreated Advanced Uveal Melanoma
• Actual Study Start Date: Oct 16, 2017
• Actual Primary Completion Date: Oct 13, 2020
• Anticipated Study Completion Date: Mar 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: IMCgp100 (tebentafusp, Kimmtrak) Biologic:IMCgp100 (Soluble gp 100-specific T cell receptor with anti - CD3 scFV: IMCgp100)	Biological: IMCgp100; 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
Active Comparator: Investigator's Choice 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	Drug: Dacarbazine; 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; Other Names: DTIC-Dome DTIC DIC Imidazole Carboxamide ; Biological: Ipilimumab; Ipilimumab is to be administered at 3 mg/kg IV infusion over 90 minutes every 3 weeks for a total of 4 treatments; Other Names: Yervoy ; Biological: Pembrolizumab; 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; Other Names: Keytruda

Outcome Measures

Primary Outcome Measures

1. Efficacy: Overall Survival [From randomization to the data cut off date of 13-Oct-2020; median follow-up duration was 14.1 months.]

   Overall survival is defined as the time from randomization to date of death due to any cause.

Secondary Outcome Measures

1. Safety: Number of Participants With Treatment Emergent Adverse Events [Safety was assessed from informed consent through 90 days after end of treatment, up to 36 months.]

   Safety was defined as the number of participants with treatment emergent adverse events, including laboratory abnormalities, ECG changes, and/or physical examination findings.

2. Efficacy: Progression Free Survival (PFS) [PFS was assessed every 3 months from randomization until disease progression or death, up to 36 months.]

   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.

3. Quality-of-Life: Change From Baseline in EQ-5D,5L Domain Scores [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.]

   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.

4. Quality-of-life: Change From Baseline in EQ-5D Visual Analogue Score (VAS) [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.]

   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.

5. Quality-of-Life: Change From Baseline in EORTC QLQ-C30 Global Health Status [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.]

   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.

6. Pharmacokinetics (PK): Tebentafusp Concentration [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.]

   Serum PK concentrations of tebentafusp were collected over time.

7. Efficacy: Objective Response Rate (ORR) [ORR will be assessed after every participant has had at least 3 assessments, conducted every 3 months, up to 5.5 years.]

   Objective response rate (ORR) is defined as the proportion of patients achieving an objective response (RECIST v1.1).

8. Efficacy: Duration of Response (DOR) [DOR will be assessed every 3 months from randomization until disease progression, assessed up to 5.5 years.]

   Duration of response (DOR) is defined as the time from first documented objective response (RECIST v1.1) until the date of documented disease progression.

9. Efficacy: Disease Control Rate (DCR) [DCR will be assessed every 3 months from randomization until disease progression, up to 5.5 years.]

   Disease control rate (DCR) is defined as the proportion of patients with either an objective response or stable disease (RECIST v1.1)

10. Pharmacokinetics: Frequency of Anti-IMCgp100 Antibody Formation [Approximately 5 assessments will be performed between first dose of IMCgp100 and end of treatment, assessed up to 5.5 years.]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 99 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria

1. Male or female patients 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 patients with localized disease. Patients may not be re-treated with an Investigator's Choice therapy that was administered as adjuvant or neoadjuvant treatment. Additionally, patients who have received nivolumab as prior adjuvant/neoadjuvant treatment should not receive pembrolizumab as Investigator's Choice therapy.

1. HLA A*0201 positive by central assay

2. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 at Screening

3. Patients have measurable disease or non-measurable disease according to RECIST v1.1

4. 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

5. Patients 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

6. Active infection requiring systemic antibiotic therapy. Patients requiring systemic antibiotics for infection must have completed therapy at least 1 week prior to the first dose of study drug

7. Known history of human immunodeficiency virus infection (HIV). Testing for HIV status is not necessary unless clinically indicated

8. 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

9. 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

10. Any medical condition that would, in the investigator's or Sponsor's judgment, prevent the patient's participation in the clinical study due to safety concerns, compliance with clinical study procedures or interpretation of study results

11. Patients 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

12. History of adrenal insufficiency

13. History of interstitial lung disease

14. History of pneumonitis that required corticosteroid treatment or current pneumonitis

15. History of colitis or inflammatory bowel disease

16. 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)

17. 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

18. Use of hematopoietic colony-stimulating growth factors (eg, 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

19. 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)

20. 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

21. Male patients 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

22. Patients who are in an institution due to official or judicial order.

23. Patients who are the investigator or any subinvestigator, research assistant, pharmacist, study coordinator, or other staff thereof, directly involved in the conduct of the study.

24. Contraindication for treatment with Investigator's Choice alternatives (dacarbazine, ipilimumab and pembrolizumab) as per applicable labelling. Patient 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCLA Medical Center	Los Angeles	California	United States	90024
2	The Angeles Clinic and Research Institute	Los Angeles	California	United States	90025
3	Byers Eye Institute, Stanford University	Palo Alto	California	United States	94303
4	California Pacific Medical Center	San Francisco	California	United States	94115
5	University of Colorado	Aurora	Colorado	United States	80045
6	University of Miami - Sylvester Comprehensive Cancer Center	Miami	Florida	United States	33136
7	Winship Cancer Institute of Emory University	Atlanta	Georgia	United States	30322
8	Northwestern University	Chicago	Illinois	United States	60611
9	The University of Chicago Medicine	Chicago	Illinois	United States	60637
10	University of Iowa	Iowa City	Iowa	United States	52242
11	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
12	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
13	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
14	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
15	Columbia University Medical Center	New York	New York	United States	10032
16	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
17	Duke University Health System	Durham	North Carolina	United States	27710
18	The Ohio State University	Columbus	Ohio	United States	43210
19	University of Oklahoma	Oklahoma City	Oklahoma	United States	73104
20	Portland Providence Medial Center	Portland	Oregon	United States	97213
21	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania	United States	19107
22	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15232
23	Houston Methodist Cancer Center	Houston	Texas	United States	77030
24	Saint Vincents Hospital	Darlinghurst	New South Wales	Australia	2010
25	Central Adelaide Local Health Network, Royal Adelaide Hospital Cancer Center	Adelaide	South Australia	Australia	5000
26	Peter MacCallum Cancer Center	Melbourne	Victoria	Australia	3000
27	Institut Roi Albert II Cliniques Universitaires St-Luc	Bruxelles		Belgium
28	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
29	Princess Margaret Cancer Centre	Toronto		Canada	M5G 2M9
30	Centre Atoine Lacassagne	Nice		France	6189
31	Institut Curie	Paris		France	75005
32	Universitaetsklinikum Koeln Dermatologie und Venerologie	Koeln	Nordrhein Westfalen	Germany	50937
33	Charite - Campus Benjamin Franklin	Berlin		Germany	12200/12203
34	Universitätsklinikum Carl Gustav Carus	Dresden		Germany	01307
35	University Hospital Essen	Essen		Germany
36	University of Hamburg	Hamburg		Germany	20246
37	Nationales Centrum für Tumorerkrankungen	Heidelberg		Germany	69120
38	Klinik und Poliklinik für Dermatologie und Allergologie	Munich		Germany	80337
39	Fondazione ICCRS	Milan		Italy	20133
40	Istituto Nazionale Tumori - IRCCS Fondazione "G. Pascale" - UOC Melanoma, Immunoterapia Oncologica e Terapie Innovative	Napoli		Italy	80131
41	LUMC Medical Oncology	Leiden		Netherlands	2333
42	Centrum Onkologii - Instytut im. Marii Sklodowskiej-Curie	Warsaw		Poland	02-781
43	Federal State Budgetary Institution N.N. Blokhin National Medical Research Center of Oncology	Moscow		Russian Federation	115478
44	Federal State Budget Institution National Medical Research Center of Oncology	Saint Petersburg		Russian Federation	197758
45	Institut Catala d'Oncologia (ICO) - L'Hospitalet	L'Hospitalet De Llobregat	ES-Spain	Spain	08908
46	Hospital Universitario La Paz	Madrid	ES-Spain	Spain	28046
47	Hospital Clínico Universitario de Santiago de Compostela	Santiago De Compostela	ES-Spain	Spain	15706
48	Hospital Universitario General de Valencia	Valencia	ES-Spain	Spain	46014
49	Hospital Universitario Virgen Macarena	Sevilla		Spain	41009
50	University of Zurich Hospital	Zürich		Switzerland	8091
51	Dnipropetrovsk State Medical Academy	Dnipropetrovs'k		Ukraine	49102
52	Kyiv Munitipal Hospital	Kyiv		Ukraine	02094
53	Uzhhorod Central City Clinical Hospital	Uzhhorod		Ukraine	8800
54	Mount Vernon Cancer Centre	Northwood	Middlesex	United Kingdom	HA6 2RN
55	The Clatterbridge Cancer Centre	Bebington	Wirral	United Kingdom	CH63 4JY
56	Beatson West of Scotland Cancer Centre	Glasgow		United Kingdom	G12 0YN

Sponsors and Collaborators

• Immunocore Ltd

Investigators

• Study Director: Mohammed Dar, Immunocore Ltd

Study Documents (Full-Text)

• Study Protocol - Mar 31, 2020
• Statistical Analysis Plan - Oct 28, 2020

More Information

Publications

None provided.

• Responsible Party: Immunocore Ltd
• ClinicalTrials.gov Identifier: NCT03070392
• Other Study ID Numbers: IMCgp100-202
• First Posted: Mar 3, 2017
• Last Update Posted: Mar 21, 2022
• Last Verified: Mar 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Immunocore Ltd: Melanoma; Uveal Cancer; IMCgp100; Immunotherapy; Tebentafusp; Ocular Melanoma; Eye Melanoma; Uveal Melanoma; Gp100; TCR; Dacarbazine; Ipilimumab; Pembrolizumab; Bispecific T cell receptor fusion protein; ImmTAC; Immune mobilizing monoclonal T cell receptor against cancer; Kimmtrak
• Additional relevant MeSH terms: Melanoma; Uveal Neoplasms; Pembrolizumab; Ipilimumab; Dacarbazine; Imidazole

Study Results

Participant Flow

Recruitment Details	A total of 378 patients were randomly assigned (2:1) to Tebentafusp (n=252) or Investigator's Choice (n=126) at 58 sites in 14 countries.
Pre-assignment Detail	The data cut-off date for this analysis was 13 October 2020. Combining participants into a single group as part of the Investigator's Choice arm was pre-specified as part of the study design.

Arm/Group Title	Tebentafusp	Investigator's Choice: Dacarbazine	Investigator's Choice: Ipilimumab	Investigator's Choice: Pembrolizumab
Arm/Group Description	Tebentafusp administered at 20 mcg at Cycle 1 Day 1, 30 mcg at Cycle 1 Day 8, and 68 mcg at Cycle 1 Day 15 by IV infusion and weekly thereafter.	Dacarbazine administered at 1,000 mg/m^2 of body surface area IV infusion every 3 weeks until confirmed disease progression or unacceptable toxicity.	Ipilimumab administered at 3 mg/kg IV infusion over 90 minutes every 3 weeks for a total of 4 treatments.	Pembrolizumab administered at 2 mg/kg IV infusion 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.
Period Title: Overall Study
STARTED	252	7	16	103
COMPLETED	0	0	10	0
NOT COMPLETED	252	7	6	103

Baseline Characteristics

Arm/Group Title	Tebentafusp	Investigator's Choice	Total
Arm/Group Description	Tebentafusp administered at 20 mcg at Cycle 1 Day 1, 30 mcg at Cycle 1 Day 8, and 68 mcg at Cycle 1 Day 15 by IV infusion and weekly thereafter.	1 of 3 Investigator's Choice options: Systemic Dacarbazine, Ipilimumab or Pembrolizumab. Dacarbazine: administered at 1,000 mg/m2 of body surface area IV infusion every 3 weeks until disease progression or unacceptable toxicity; Ipilimumab: administered at 3 mg/kg IV infusion over 90 minutes every 3 weeks for a total of 4 treatments; Pembrolizumab: 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.	Total of all reporting groups
Overall Participants	252	126	378
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	61.3 (11.9)	63.6 (10.7)	62.1 (11.6)
Sex: Female, Male (Count of Participants)
Female	124 49.2%	64 50.8%	188 49.7%
Male	128 50.8%	62 49.2%	190 50.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 0.8%	1 0.3%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	222 88.1%	107 84.9%	329 87%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	30 11.9%	18 14.3%	48 12.7%

Outcome Measures

1. Primary Outcome

Title	Efficacy: Overall Survival
Description	Overall survival is defined as the time from randomization to date of death due to any cause.
Time Frame	From randomization to the data cut off date of 13-Oct-2020; median follow-up duration was 14.1 months.

Outcome Measure Data

Analysis Population Description

The Intent-to-treat (ITT) Analysis Set comprises all participants assigned to treatment analyzed by the treatment assignment whether or not the participant received the assigned treatment. Combining participants into a single group as part of the Investigator's Choice arm was pre-specified as part of the study design; therefore, data per different treatments were not analyzed.

Arm/Group Title	Tebentafusp	Investigator's Choice
Arm/Group Description	Tebentafusp administered at 20 mcg at Cycle 1 Day 1, 30 mcg at Cycle 1 Day 8, and 68 mcg at Cycle 1 Day 15 by IV infusion and weekly thereafter.	1 of 3 Investigator's Choice options: Systemic Dacarbazine, Ipilimumab or Pembrolizumab. Dacarbazine: administered at 1,000 mg/m2 of body surface area IV infusion every 3 weeks until disease progression or unacceptable toxicity; Ipilimumab: administered at 3 mg/kg IV infusion over 90 minutes every 3 weeks for a total of 4 treatments; Pembrolizumab: 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.
Measure Participants	252	126
Median (95% Confidence Interval) [Months]	21.7	16.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tebentafusp, Investigator's Choice
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.51
	Confidence Interval	(2-Sided) 95%; 0.37 to 0.71
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Safety: Number of Participants With Treatment Emergent Adverse Events
Description	Safety was defined as the number of participants with treatment emergent adverse events, including laboratory abnormalities, ECG changes, and/or physical examination findings.
Time Frame	Safety was assessed from informed consent through 90 days after end of treatment, up to 36 months.

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set includes all randomized participants who received at least 1 full or partial dose of tebentafusp or investigator's choice. Combining participants into a single group as part of the Investigator's Choice arm was pre-specified as part of the study design; therefore, data per different treatments were not analyzed.

Arm/Group Title	Tebentafusp	Investigator's Choice
Arm/Group Description	Tebentafusp administered at 20 mcg at Cycle 1 Day 1, 30 mcg at Cycle 1 Day 8, and 68 mcg at Cycle 1 Day 15 by IV infusion and weekly thereafter.	1 of 3 Investigator's Choice options: Systemic Dacarbazine, Ipilimumab or Pembrolizumab. Dacarbazine: administered at 1,000 mg/m2 of body surface area IV infusion every 3 weeks until disease progression or unacceptable toxicity; Ipilimumab: administered at 3 mg/kg IV infusion over 90 minutes every 3 weeks for a total of 4 treatments; Pembrolizumab: 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.
Measure Participants	245	111
Count of Participants [Participants]	245 97.2%	105 83.3%

3. Secondary Outcome

Title	Efficacy: Progression Free Survival (PFS)
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.
Time Frame	PFS was assessed every 3 months from randomization until disease progression or death, up to 36 months.

Outcome Measure Data

Analysis Population Description

The Intent-to-treat (ITT) Analysis Set comprises all participants assigned to treatment analyzed by the treatment assignment whether or not the participant received the assigned treatment. Combining participants into a single group as part of the Investigator's Choice arm was pre-specified as part of the study design; therefore, data per different treatments were not analyzed.

Arm/Group Title	Tebentafusp	Investigator's Choice
Arm/Group Description	Tebentafusp administered at 20 mcg at Cycle 1 Day 1, 30 mcg at Cycle 1 Day 8, and 68 mcg at Cycle 1 Day 15 by IV infusion and weekly thereafter.	1 of 3 Investigator's Choice options: Systemic Dacarbazine, Ipilimumab or Pembrolizumab. Dacarbazine: administered at 1,000 mg/m2 of body surface area IV infusion every 3 weeks until disease progression or unacceptable toxicity; Ipilimumab: administered at 3 mg/kg IV infusion over 90 minutes every 3 weeks for a total of 4 treatments; Pembrolizumab: 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.
Measure Participants	252	126
Median (95% Confidence Interval) [Months]	3.3	2.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tebentafusp, Investigator's Choice
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0139
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.73
	Confidence Interval	(2-Sided) 95%; 0.58 to 0.94
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Quality-of-Life: Change From Baseline in EQ-5D,5L Domain Scores
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.
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.

Outcome Measure Data

Analysis Population Description

The Intent-to-treat (ITT) Analysis Set comprises all participants assigned to treatment analyzed by the treatment assignment whether or not the participant received the assigned treatment. Combining participants into a single group as part of the Investigator's Choice arm was pre-specified as part of the study design; therefore, data per different treatments were not analyzed.

Arm/Group Title	Tebentafusp	Investigator's Choice
Arm/Group Description	Tebentafusp administered at 20 mcg at Cycle 1 Day 1, 30 mcg at Cycle 1 Day 8, and 68 mcg at Cycle 1 Day 15 by IV infusion and weekly thereafter.	1 of 3 Investigator's Choice options: Systemic Dacarbazine, Ipilimumab or Pembrolizumab. Dacarbazine: administered at 1,000 mg/m2 of body surface area IV infusion every 3 weeks until disease progression or unacceptable toxicity; Ipilimumab: administered at 3 mg/kg IV infusion over 90 minutes every 3 weeks for a total of 4 treatments; Pembrolizumab: 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.
Measure Participants	252	126
Mobility - Baseline Cycle 1	1.2 (0.62)	1.3 (0.55)
Mobility - Change at Cycle 3	-0.1 (0.66)	0.1 (0.47)
Mobility - Change at Cycle 5	0.0 (0.73)	0.3 (0.65)
Mobility - Change at Cycle 9	0.0 (0.91)	0.0 (0.55)
Mobility - Change at Cycle 13	-0.1 (0.60)	0.3 (0.87)
Mobility - Change at Cycle 17	0.3 (0.57)	0.2 (0.41)
Mobility - Change at Cycle 21	0.0 (0.58)	0.5 (0.71)
Mobility - Change at Cycle 25	0.1 (0.64)	0.0 (0.00)
Mobility - Change at Cycle 29	0.0 (0.50)	0.0 (0.00)
Mobility - Change at EOT	0.3 (0.73)	0.4 (0.99)
Self-care - Baseline Cycle 1	1.1 (0.45)	1.1 (0.29)
Self-care - Change at Cycle 3	0.0 (0.49)	0.0 (0.26)
Self-care - Change at Cycle 5	0.0 (0.42)	0.0 (0.00)
Self-care - Change at Cycle 9	0.0 (0.58)	0.0 (0.00)
Self-care - Change at Cycle 13	0.1 (0.52)	0.1 (0.33)
Self-care - Change at Cycle 17	0.1 (0.68)	0.0 (0.00)
Self-care - Change at Cycle 21	0.0 (0.00)	0.0 (0.00)
Self-care - Change at Cycle 25	0.0 (0.00)	0.0 (0.00)
Self-care - Change at Cycle 29	0.0 (0.00)	0.0 (0.00)
Self-care - Change at EOT	0.1 (0.60)	0.1 (0.56)
Usual activities - Baseline Cycle 1	1.2 (0.53)	1.3 (0.55)
Usual activities - Change at Cycle 3	0.2 (0.59)	0.1 (0.73)
Usual activities - Change at Cycle 5	0.1 (0.61)	0.2 (0.61)
Usual activities - Change at Cycle 9	0.2 (0.87)	0.1 (0.53)
Usual activities - Change at Cycle 13	0.3 (0.79)	0.1 (0.60)
Usual activities - Change at Cycle 17	0.5 (0.80)	0.2 (0.41)
Usual activities - Change at Cycle 21	0.3 (0.48)	0.0 (0.00)
Usual activities - Change at Cycle 25	0.3 (0.46)	0.0 (0.00)
Usual activities - Change at Cycle 29	0.2 (0.44)	0.0 (0.00)
Usual activities - Change at EOT	0.4 (0.77)	0.5 (0.87)
Pain/Discomfort - Baseline Cycle 1	1.5 (0.71)	1.5 (0.73)
Pain/Discomfort - Change at Cycle 3	0.0 (0.75)	0.1 (0.73)
Pain/Discomfort - Change at Cycle 5	0.0 (0.65)	0.2 (0.72)
Pain/Discomfort - Change at Cycle 9	0.1 (0.73)	-0.1 (0.73)
Pain/Discomfort - Change at Cycle 13	0.1 (0.51)	0.1 (0.93)
Pain/Discomfort - Change at Cycle 17	0.4 (0.85)	0.3 (0.52)
Pain/Discomfort - Change at Cycle 21	0.2 (0.55)	0.0 (0.00)
Pain/Discomfort - Change at Cycle 25	0.0 (0.53)	1.0 (NA)
Pain/Discomfort - Change at Cycle 29	0.1 (0.60)	0.5 (0.71)
Pain/Discomfort - Change at EOT	0.2 (0.87)	0.4 (1.10)
Anxiety/Depression - Baseline Cycle 1	1.8 (0.94)	1.7 (0.89)
Anxiety/Depression - Change at Cycle 3	-0.2 (0.77)	-0.3 (0.55)
Anxiety/Depression - Change at Cycle 5	-0.2 (0.74)	0.0 (0.61)
Anxiety/Depression - Change at Cycle 9	-0.3 (0.80)	0.1 (0.77)
Anxiety/Depression - Change at Cycle 13	-0.4 (0.77)	-0.1 (0.60)
Anxiety/Depression - Change at Cycle 17	-0.4 (0.85)	0.0 (0.00)
Anxiety/Depression - Change at Cycle 21	-0.5 (0.88)	0.0 (0.00)
Anxiety/Depression - Change at Cycle 25	-0.4 (0.74)	0.0 (NA)
Anxiety/Depression - Change at Cycle 29	-0.6 (0.88)	0.5 (0.71)
Anxiety/Depression - Change at EOT	0.3 (0.94)	0.2 (1.07)

5. Secondary Outcome

Title	Quality-of-life: Change From Baseline in EQ-5D Visual Analogue Score (VAS)
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.
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.

Outcome Measure Data

Analysis Population Description

The Intent-to-treat (ITT) Analysis Set comprises all participants assigned to treatment analyzed by the treatment assignment whether or not the participant received the assigned treatment. Combining participants into a single group as part of the Investigator's Choice arm was pre-specified as part of the study design; therefore, data per different treatments were not analyzed.

Arm/Group Title	Tebentafusp	Investigator's Choice
Arm/Group Description	Tebentafusp administered at 20 mcg at Cycle 1 Day 1, 30 mcg at Cycle 1 Day 8, and 68 mcg at Cycle 1 Day 15 by IV infusion and weekly thereafter.	1 of 3 Investigator's Choice options: Systemic Dacarbazine, Ipilimumab or Pembrolizumab. Dacarbazine: administered at 1,000 mg/m2 of body surface area IV infusion every 3 weeks until disease progression or unacceptable toxicity; Ipilimumab: administered at 3 mg/kg IV infusion over 90 minutes every 3 weeks for a total of 4 treatments; Pembrolizumab: 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.
Measure Participants	252	126
Baseline Cycle 1	81.0 (16.36)	80.4 (18.31)
Change at Cycle 3	0.4 (14.69)	-0.8 (14.28)
Change at Cycle 5	0.6 (15.61)	-0.7 (14.38)
Change at Cycle 9	-0.9 (19.81)	-3.3 (13.30)
Change at Cycle 13	-2.0 (16.48)	-2.6 (8.37)
Change at Cycle 17	-10.2 (20.93)	-8.5 (33.82)
Change at Cycle 21	-1.8 (14.52)	-1.0 (5.66)
Change at Cycle 25	-13.6 (19.43)	-4.0 (NA)
Change at Cycle 29	0.0 (9.25)	-2.0 (1.41)
Change at EOT	-10.1 (22.53)	-11.7 (21.40)

6. Secondary Outcome

Title	Quality-of-Life: Change From Baseline in EORTC QLQ-C30 Global Health Status
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.
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.

Outcome Measure Data

Analysis Population Description

The Intent-to-treat (ITT) Analysis Set comprises all participants assigned to treatment analyzed by the treatment assignment whether or not the participant received the assigned treatment. Combining participants into a single group as part of the Investigator's Choice arm was pre-specified as part of the study design; therefore, data per different treatments were not analyzed.

Arm/Group Title	Tebentafusp	Investigator's Choice
Arm/Group Description	Tebentafusp administered at 20 mcg at Cycle 1 Day 1, 30 mcg at Cycle 1 Day 8, and 68 mcg at Cycle 1 Day 15 by IV infusion and weekly thereafter.	1 of 3 Investigator's Choice options: Systemic Dacarbazine, Ipilimumab or Pembrolizumab. Dacarbazine: administered at 1,000 mg/m2 of body surface area IV infusion every 3 weeks until disease progression or unacceptable toxicity; Ipilimumab: administered at 3 mg/kg IV infusion over 90 minutes every 3 weeks for a total of 4 treatments; Pembrolizumab: 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.
Measure Participants	252	126
Baseline Cycle 1	76.108 (20.233)	74.872 (20.439)
Change at Cycle 3	0.952 (16.274)	-0.238 (14.919)
Change at Cycle 5	-1.152 (20.797)	-10.227 (22.557)
Change at Cycle 9	-2.193 (19.577)	-8.333 (13.176)
Change at Cycle 13	-5.625 (17.641)	-10.185 (16.017)
Change at Cycle 17	-10.185 (28.087)	-4.167 (6.972)
Change at Cycle 21	0.758 (18.429)	-4.167 (5.893)
Change at Cycle 25	-2.381 (27.936)	0.00 (0.00)
Change at Cycle 29	-8.333 (19.720)	0.00 (0.00)
Change at EOT	-10.417 (20.911)	-10.539 (23.148)

7. Secondary Outcome

Title	Pharmacokinetics (PK): Tebentafusp Concentration
Description	Serum PK concentrations of tebentafusp were collected over time.
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.

Outcome Measure Data

Analysis Population Description

The PK Analysis Set included participants in the Safety Analysis Set who had at least 1 measurable PK concentration and who had relevant date, time, and dosing data for the sample.

Arm/Group Title	Tebentafusp
Arm/Group Description	Tebentafusp administered at 20 mcg at Cycle 1 Day 1, 30 mcg at Cycle 1 Day 8, and 68 mcg at Cycle 1 Day 15 by IV infusion and weekly thereafter.
Measure Participants	231
Cycle 1 Day 1 - End of Infusion	4201.929 (0.6)
Cycle 1 Day 1 - 12 to 24 hours post-infusion	505.100 (0.7)
Cycle 1 Day 8 - End of Infusion	5787.139 (0.4)
Cycle 1 Day 8 - 12 to 24 hours post-infusion	738.602 (0.7)
Cycle 1 Day 15 - End of Infusion	13715.914 (0.5)
Cycle 1 Day 15 - 12 to 24 hours post-infusion	1685.354 (0.6)

8. Secondary Outcome

Title	Efficacy: Objective Response Rate (ORR)
Description	Objective response rate (ORR) is defined as the proportion of patients achieving an objective response (RECIST v1.1).
Time Frame	ORR will be assessed after every participant has had at least 3 assessments, conducted every 3 months, up to 5.5 years.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

9. Secondary Outcome

Title	Efficacy: Duration of Response (DOR)
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.
Time Frame	DOR will be assessed every 3 months from randomization until disease progression, assessed up to 5.5 years.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

10. Secondary Outcome

Title	Efficacy: Disease Control Rate (DCR)
Description	Disease control rate (DCR) is defined as the proportion of patients with either an objective response or stable disease (RECIST v1.1)
Time Frame	DCR will be assessed every 3 months from randomization until disease progression, up to 5.5 years.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

11. Secondary Outcome

Title	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Approximately 36 months.
Adverse Event Reporting Description	The Safety Analysis Set included all randomized participants who received at least 1 full or partial dose of tebentafusp or investigator's choice. Combining participants into a single group (Investigator's Choice) was pre-specified as part of the study design and data for each treatment in that arm were not analyzed separately. Adverse events were defined as events that were new or worsened during the on-treatment period.
Arm/Group Title	Tebentafusp		Investigator's Choice
Arm/Group Description	Tebentafusp administered at 20 mcg at Cycle 1 Day 1, 30 mcg at Cycle 1 Day 8, and 68 mcg at Cycle 1 Day 15 by IV infusion and weekly thereafter.		1 of 3 Investigator's Choice options: Systemic Dacarbazine, Ipilimumab or Pembrolizumab. Dacarbazine: administered at 1,000 mg/m2 of body surface area IV infusion every 3 weeks until disease progression or unacceptable toxicity; Ipilimumab: administered at 3 mg/kg IV infusion over 90 minutes every 3 weeks for a total of 4 treatments; Pembrolizumab: 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.
All Cause Mortality
	Tebentafusp		Investigator's Choice
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	84/245 (34.3%)		57/111 (51.4%)
Serious Adverse Events
	Tebentafusp		Investigator's Choice
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	69/245 (28.2%)		26/111 (23.4%)
Blood and lymphatic system disorders
Anemia	1/245 (0.4%)	2	0/111 (0%)	0
Cardiac disorders
Left ventricular dysfunction	0/245 (0%)	0	1/111 (0.9%)	1
Endocrine disorders
Hypopituitarism	0/245 (0%)	0	1/111 (0.9%)	1
Eye disorders
Diplopia	1/245 (0.4%)	1	0/111 (0%)	0
Periorbital edema	1/245 (0.4%)	1	0/111 (0%)	0
Uveitis	0/245 (0%)	0	1/111 (0.9%)	1
Gastrointestinal disorders
Abdominal pain	2/245 (0.8%)	4	3/111 (2.7%)	3
Abdominal pain upper	1/245 (0.4%)	1	0/111 (0%)	0
Colitis	0/245 (0%)	0	1/111 (0.9%)	1
Diarrhea	0/245 (0%)	0	1/111 (0.9%)	1
Enteritis	0/245 (0%)	0	1/111 (0.9%)	1
Gastritis	0/245 (0%)	0	1/111 (0.9%)	1
Nausea	4/245 (1.6%)	6	1/111 (0.9%)	2
Vomiting	2/245 (0.8%)	3	0/111 (0%)	0
General disorders
Asthenia	1/245 (0.4%)	1	0/111 (0%)	0
Fatigue	1/245 (0.4%)	3	0/111 (0%)	0
Gait disturbance	0/245 (0%)	0	1/111 (0.9%)	1
General physical health deterioration	1/245 (0.4%)	1	0/111 (0%)	0
Pyrexia	6/245 (2.4%)	6	2/111 (1.8%)	2
Hepatobiliary disorders
Biliary obstruction	1/245 (0.4%)	3	0/111 (0%)	0
Hepatic failure	1/245 (0.4%)	1	0/111 (0%)	0
Hepatic necrosis	1/245 (0.4%)	1	0/111 (0%)	0
Hepatic pain	1/245 (0.4%)	1	0/111 (0%)	0
Hepatomegaly	0/245 (0%)	0	1/111 (0.9%)	1
Hepatotoxicity	2/245 (0.8%)	18	0/111 (0%)	0
Hyperbilirubinemia	2/245 (0.8%)	3	3/111 (2.7%)	5
Hypertransaminasemia	1/245 (0.4%)	5	0/111 (0%)	0
Immune system disorders
Anaphylactic reaction	1/245 (0.4%)	1	0/111 (0%)	0
Cytokine release syndrome	24/245 (9.8%)	51	0/111 (0%)	0
Infections and infestations
Anorectal infection	0/245 (0%)	0	1/111 (0.9%)	1
Appendicitis	1/245 (0.4%)	1	0/111 (0%)	0
COVID-19	1/245 (0.4%)	1	0/111 (0%)	0
Erysipelas	1/245 (0.4%)	2	0/111 (0%)	0
Pneumonia	0/245 (0%)	0	1/111 (0.9%)	1
Pneumonia mycoplasmal	0/245 (0%)	0	1/111 (0.9%)	1
Salmonella sepsis	1/245 (0.4%)	1	0/111 (0%)	0
Injury, poisoning and procedural complications
Fall	0/245 (0%)	0	1/111 (0.9%)	1
Procedural pain	1/245 (0.4%)	1	1/111 (0.9%)	1
Investigations
Alanine aminotransferase increased	1/245 (0.4%)	1	0/111 (0%)	0
Amylase increased	1/245 (0.4%)	2	0/111 (0%)	0
Aspartate aminotransferase increased	1/245 (0.4%)	1	0/111 (0%)	0
Blood creatinine increased	2/245 (0.8%)	2	0/111 (0%)	0
Lipase increased	0/245 (0%)	0	1/111 (0.9%)	1
Metabolism and nutrition disorders
Dehydration	0/245 (0%)	0	2/111 (1.8%)	2
Hyperglycemia	0/245 (0%)	0	1/111 (0.9%)	1
Tumor lysis syndrome	1/245 (0.4%)	1	0/111 (0%)	0
Musculoskeletal and connective tissue disorders
Bone pain	0/245 (0%)	0	1/111 (0.9%)	1
Pathological fracture	0/245 (0%)	0	1/111 (0.9%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Meningioma	1/245 (0.4%)	1	0/111 (0%)	0
Metastases to abdominal cavity	0/245 (0%)	0	1/111 (0.9%)	1
Neoplasm progression	0/245 (0%)	0	1/111 (0.9%)	1
Tumor pain	2/245 (0.8%)	3	0/111 (0%)	0
Nervous system disorders
Brain edema	1/245 (0.4%)	1	0/111 (0%)	0
Dizziness	1/245 (0.4%)	1	0/111 (0%)	0
Intracranial mass	0/245 (0%)	0	1/111 (0.9%)	2
Lethargy	0/245 (0%)	0	1/111 (0.9%)	1
Motor dysfunction	1/245 (0.4%)	2	0/111 (0%)	0
Presyncope	1/245 (0.4%)	2	0/111 (0%)	0
Seizure	0/245 (0%)	0	1/111 (0.9%)	1
Spinal cord compression	1/245 (0.4%)	2	0/111 (0%)	0
Psychiatric disorders
Mental status changes	1/245 (0.4%)	1	0/111 (0%)	0
Renal and urinary disorders
Acute kidney injury	1/245 (0.4%)	2	0/111 (0%)	0
Renal failure	1/245 (0.4%)	1	0/111 (0%)	0
Reproductive system and breast disorders
Scrotal inflammation	1/245 (0.4%)	1	0/111 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	0/245 (0%)	0	1/111 (0.9%)	1
Dyspnea	2/245 (0.8%)	2	0/111 (0%)	0
Pleurisy	0/245 (0%)	0	1/111 (0.9%)	1
Pneumonitis	0/245 (0%)	0	1/111 (0.9%)	2
Pulmonary embolism	1/245 (0.4%)	2	3/111 (2.7%)	4
Pulmonary edema	1/245 (0.4%)	1	0/111 (0%)	0
Sleep apnea syndrome	0/245 (0%)	0	1/111 (0.9%)	1
Skin and subcutaneous tissue disorders
Pruritus	1/245 (0.4%)	1	0/111 (0%)	0
Rash	6/245 (2.4%)	10	0/111 (0%)	0
Rash maculo-papular	4/245 (1.6%)	13	0/111 (0%)	0
Rash papular	1/245 (0.4%)	2	0/111 (0%)	0
Skin reaction	1/245 (0.4%)	1	0/111 (0%)	0
Urticaria	1/245 (0.4%)	2	0/111 (0%)	0
Vascular disorders
Hypotension	5/245 (2%)	6	0/111 (0%)	0
Other (Not Including Serious) Adverse Events
	Tebentafusp		Investigator's Choice
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	245/245 (100%)		102/111 (91.9%)
Blood and lymphatic system disorders
Anemia	25/245 (10.2%)	62	4/111 (3.6%)	4
Lymphopenia	24/245 (9.8%)	51	3/111 (2.7%)	4
Thrombocytopenia	5/245 (2%)	7	6/111 (5.4%)	10
Cardiac disorders
Tachycardia	24/245 (9.8%)	45	3/111 (2.7%)	3
Endocrine disorders
Hyperthyroidism	2/245 (0.8%)	2	13/111 (11.7%)	16
Hypothyroidism	3/245 (1.2%)	3	12/111 (10.8%)	15
Eye disorders
Periorbital edema	26/245 (10.6%)	51	1/111 (0.9%)	1
Gastrointestinal disorders
Abdominal pain	59/245 (24.1%)	92	14/111 (12.6%)	21
Abdominal pain upper	50/245 (20.4%)	79	14/111 (12.6%)	21
Constipation	44/245 (18%)	65	13/111 (11.7%)	15
Diarrhea	61/245 (24.9%)	120	22/111 (19.8%)	45
Dry mouth	8/245 (3.3%)	9	6/111 (5.4%)	6
Dyspepsia	20/245 (8.2%)	28	5/111 (4.5%)	5
Nausea	119/245 (48.6%)	288	28/111 (25.2%)	44
Vomiting	73/245 (29.8%)	163	10/111 (9%)	19
General disorders
Asthenia	38/245 (15.5%)	71	9/111 (8.1%)	11
Chills	117/245 (47.8%)	378	4/111 (3.6%)	4
Face edema	25/245 (10.2%)	39	2/111 (1.8%)	2
Fatigue	124/245 (50.6%)	352	39/111 (35.1%)	53
Influenza like illness	18/245 (7.3%)	75	2/111 (1.8%)	2
Edema peripheral	66/245 (26.9%)	119	3/111 (2.7%)	3
Pyrexia	186/245 (75.9%)	682	7/111 (6.3%)	11
Hepatobiliary disorders
Hepatic pain	15/245 (6.1%)	41	4/111 (3.6%)	4
Hyperbilirubinemia	26/245 (10.6%)	56	6/111 (5.4%)	6
Immune system disorders
Cytokine release syndrome	34/245 (13.9%)	91	0/111 (0%)	0
Infections and infestations
Nasopharyngitis	20/245 (8.2%)	24	1/111 (0.9%)	1
Urinary tract infection	14/245 (5.7%)	19	5/111 (4.5%)	5
Investigations
Alanine aminotransferase increased	50/245 (20.4%)	127	12/111 (10.8%)	19
Aspartate aminotransferase increased	55/245 (22.4%)	134	11/111 (9.9%)	19
Blood alkaline phosphatase increased	23/245 (9.4%)	60	3/111 (2.7%)	4
Blood creatinine increased	13/245 (5.3%)	26	3/111 (2.7%)	3
Blood lactate dehydrogenase increased	13/245 (5.3%)	20	3/111 (2.7%)	8
Lipase increased	35/245 (14.3%)	73	7/111 (6.3%)	12
Weight decreased	16/245 (6.5%)	16	7/111 (6.3%)	11
Metabolism and nutrition disorders
Decreased appetite	45/245 (18.4%)	56	15/111 (13.5%)	17
Hypokalemia	18/245 (7.3%)	24	3/111 (2.7%)	3
Hypomagnesemia	19/245 (7.8%)	31	1/111 (0.9%)	1
Hypophosphatemia	27/245 (11%)	52	2/111 (1.8%)	5
Musculoskeletal and connective tissue disorders
Arthralgia	53/245 (21.6%)	97	18/111 (16.2%)	30
Back pain	45/245 (18.4%)	56	9/111 (8.1%)	14
Muscle spasms	14/245 (5.7%)	30	0/111 (0%)	0
Myalgia	24/245 (9.8%)	40	7/111 (6.3%)	9
Pain in extremity	24/245 (9.8%)	36	3/111 (2.7%)	3
Nervous system disorders
Dizziness	26/245 (10.6%)	46	9/111 (8.1%)	12
Headache	75/245 (30.6%)	135	11/111 (9.9%)	15
Parasthesia	27/245 (11%)	53	1/111 (0.9%)	1
Psychiatric disorders
Anxiety	13/245 (5.3%)	14	2/111 (1.8%)	2
Insomnia	22/245 (9%)	24	6/111 (5.4%)	6
Respiratory, thoracic and mediastinal disorders
Cough	44/245 (18%)	67	11/111 (9.9%)	12
Dyspnea	31/245 (12.7%)	42	7/111 (6.3%)	7
Oropharyngeal pain	16/245 (6.5%)	20	1/111 (0.9%)	1
Skin and subcutaneous tissue disorders
Alopecia	21/245 (8.6%)	22	2/111 (1.8%)	2
Dry skin	77/245 (31.4%)	106	4/111 (3.6%)	4
Erythema	60/245 (24.5%)	120	1/111 (0.9%)	1
Hair color changes	48/245 (19.6%)	62	0/111 (0%)	0
Night sweats	13/245 (5.3%)	17	1/111 (0.9%)	1
Pruritus	168/245 (68.6%)	536	26/111 (23.4%)	33
Rash	132/245 (53.9%)	603	18/111 (16.2%)	25
Rash maculo-papular	75/245 (30.6%)	343	9/111 (8.1%)	10
Skin exfoliation	51/245 (20.8%)	80	2/111 (1.8%)	2
Skin hyperpigmentation	19/245 (7.8%)	24	2/111 (1.8%)	2
Skin hypopigmentation	22/245 (9%)	26	2/111 (1.8%)	2
Vitiligo	40/245 (16.3%)	45	4/111 (3.6%)	5
Vascular disorders
Flushing	25/245 (10.2%)	34	1/111 (0.9%)	2
Hypertension	38/245 (15.5%)	91	8/111 (7.2%)	8
Hypotension	91/245 (37.1%)	212	3/111 (2.7%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.