Tebentafusp Regimen Versus Investigator’s Choice in Previously Treated Advanced Melanoma (TEBE-AM)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Immunocore Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

1 Sep 2023 → ongoing

Decision date (initial)

2023-11-13

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Immunocore Limited

External identifiers

EU CT number

2022-502732-39-00

ClinicalTrials.gov

NCT05549297

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacodynamic, Pharmacokinetic, Efficacy

To demonstrate OS of tebentafusp monotherapy versus Investigator’s Choice, and of tebentafusp in combination with pembrolizumab versus Investigator’s Choice

Secondary objectives 6

1. To demonstrate ctDNA reduction in a greater percentage of participants for tebentafusp monotherapy versus Investigator’s Choice and for tebentafusp in combination with pembrolizumab versus Investigator’s Choice
2. To characterize the safety and tolerability of tebentafusp as monotherapy and in combination with pembrolizumab in participants with non-ocular advanced melanoma
3. To understand the impact of treatment with tebentafusp monotherapy versus Investigator’s Choice and with tebentafusp in combination with pembrolizumab versus Investigator’s Choice in symptoms and quality of life
4. To characterize the PK of tebentafusp as monotherapy and in combination with pembrolizumab
5. To characterize the ADA to tebentafusp as monotherapy and in combination with pembrolizumab
6. To assess the incidence of Grade ≥ 2 CRS with tebentafusp as monotherapy and in combination with pembrolizumab following standardized steroid premedication regimen

Conditions and MedDRA coding

Previously treated non-ocular advanced melanoma

Study design 2 periods

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 18 years of age or older
2. HLA-A*02:01-positive
3. Unresectable Stage III or Stage IV non-ocular melanoma
4. A newly obtained (preferred) or archival tumor tissue sample has been provided
5. Either measurable or non-measurable disease per RECIST v1.1
6. ECOG performance status score of 0 or 1
7. Male and female participants of childbearing potential who are sexually active with a non-sterilized partner must agree to use highly effective methods of contraception
8. Participants must be capable of giving signed informed consent that includes compliance with the requirements and restrictions listed in the ICF and in the protocol.
9. Participants must agree to provide all necessary samples for biomarker analysis

Exclusion criteria 21

1. Diagnosis of ocular or metastatic uveal melanoma
2. History of a malignant disease other than those being treated in this study (with exceptions)
3. Ineligible to be retreated with pembrolizumab due to a treatment-related AE while on a prior anti-PD(L)1 regimen
4. Known untreated or symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis
5. Previous severe hypersensitivity reaction to treatment with another monoclonal antibody (mAb)
6. Clinically significant pulmonary disease or impaired lung function
7. Clinically significant cardiac disease or impaired cardiac function
8. Active autoimmune disease requiring immunosuppressive treatment within 2 years of screening
9. 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
10. Known psychiatric or substance abuse disorders
11. History (within the last year) of substance abuse (including alcohol)
12. Pregnant or lactating women
13. Prior treatment with a licensed or investigative Immune-mobilizing monoclonal T cell receptor Against Cancer (ImmTAC) medication
14. Non adequate washout from prior medications
15. Ongoing Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥ 2 clinically significant AEs due to prior cancer therapeutics
16. Systemic treatment with steroids or any other immunosuppressive drug within 2 weeks of the planned first dose of study intervention (with exceptions)
17. Participants who have not received required prior anticancer therapies: a. All participants must have received at least 2 doses of an approved anti-PD(L)1 mAb: i. The anti-PD(L)1 mAb may have been administered as monotherapy or in combination with another checkpoint inhibitor or other therapies, ii. The anti-PD(L)1 mAb may have been administered in the adjuvant setting or for treatment of unresectable / metastatic disease, iii. All participants must have documented disease progression, according to RECIST v1.1, during treatment or within 6 months of the last dose of an anti-PD(L)1 mAb b. All participants must have received prior treatment with an approved anti-CTL4A mAb, which may have been a part of an anti-PD(L)1 regimen or as monotherapy. c. Participants with an activating BRAF V600 mutation must have received a prior BRAF/MEK inhibitor regimen.
18. History of tuberculosis or human immunodeficiency virus (HIV) infection
19. History of chronic viral infections
20. Out-of-range screening laboratory values
21. History of allogenic tissue/solid organ transplant

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall survival

Secondary endpoints 6

1. ctDNA reduction on treatment relative to baseline
2. Incidence and severity of AEs, SAEs, and changes from baseline in laboratory parameters, vital signs, and ECGs Dose interruptions reductions, dose intensity and discontinuation of all administered agents
3. Incidence of Grade ≥ 2 CRS based on ASTCT grade, time to onset, duration of defined CRS component events, and incidence of prolonged hospitalization
4. Patient-reported symptoms and health-related quality of life according to the EORTC-QLQ-C30 and general health status according to the EQ-5D-5L questionnaires.
5. Tebentafusp PK parameters (eg, Cmax, Tmax, Cavg, t1/2)
6. Incidence of anti-tebentafusp antibodies

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Auxiliary 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Immunocore Limited

Sponsor organisation

Immunocore Limited

Address

92 Park Drive, Milton Milton

City

Abingdon

Postcode

OX14 4RY

Country

United Kingdom

Scientific contact point

Organisation

Immunocore Limited

Contact name

Nicola McKelvie

Public contact point

Organisation

Immunocore Limited

Contact name

Information Desk

Third parties 6

Locations

7 EU/EEA countries · 39 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 87 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

12 submissions — initial application plus substantial / non-substantial modifications