Phase 2 Platform Study of Novel Immunotherapy Combinations as First-Line Treatment in Participants with PD-L1 Positive Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Glaxosmithkline Research & Development Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

19 Jan 2024 → ongoing

Decision date (initial)

2023-12-11

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

GlaxoSmithKline Research & Development Limited

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate the antitumor activity of novel immunotherapy combinations compared with dostarlimab in participants with PD-L1 positive R/M HNSCC

Conditions and MedDRA coding

Neoplasms, Head and Neck

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Have histologically or cytologically-confirmed HNSCC that is R/M and considered incurable by local therapies. a. Subjects must not have had prior systemic therapy administered in the R/M setting. Chemoradiation therapy which was completed more than 4 months prior to signing consent if given as part of multimodal treatment for locally advanced disease is allowed. b. The eligible primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx. c. Subjects may not have a primary tumor site of nasopharynx (any histology).
2. Has measurable (target) disease based on RECIST 1.1 (Section 10.10 of protocol), as determined by the investigator.
3. Has an ECOG PS (Section 10.6 of protocol) of 0 or 1.
4. Provides a tumor tissue sample obtained at the time of or after the initial diagnosis of R/M HNSCC. A fresh tumor tissue sample obtained within 90 days of screening is highly preferred. If fresh biopsy is not possible, an archival tumor specimen (≤2 years old) is acceptable even if this predates the R/M diagnosis. Biopsies obtained prior to the administration of any systemic therapy administered for the treatment of a participant’s tumor (such as neoadjuvant/adjuvant therapy) are not acceptable. Needle or excisional biopsies or resected tissue is required. Cytological specimens such as fine needle aspirates, bone marrow samples, or cell blocks are not acceptable. Bone specimen is not acceptable.
5. Has tumor PD-L1 expression
6. Provides a tumor tissue sample obtained at the time of or after the initial diagnosis of R/M HNSCC. A fresh tumor tissue sample obtained within 90 days of screening is highly preferred. If fresh biopsy is not possible, an archival tumor specimen is acceptable unless it was obtained prior to administration of chemoradiation for the treatment of a participant’s tumour. Needle or excisional biopsies or resected tissue is required. Cytological specimens such as fine needle aspirates, bone marrow samples, or cell blocks are not acceptable. Bone specimen is not acceptable.

Exclusion criteria 6

1. Has received prior therapy with any immune checkpoint inhibitors, including antibodies or drugs targeting PD-1, PD-L1, CTLA-4, TIGIT, CD96, or other immune checkpoint pathways.
2. Participants with previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, esophageal, colon, endometrial, cervical/dysplasia, melanoma, or breast) unless a complete remission was achieved at least 2 years prior to study entry AND no additional therapy is required during the study period. Note: Participants are allowed if they have low-risk early-stage prostate cancer defined as follows: Stage T1c or T2a with a Gleason score ≤6 and prostatic-specific antigen <10 ng/mL either treated with definitive intent or untreated in active surveillance that has been stable for the past year prior to randomization. Additionally, participants are allowed if they have low risk intrathyroidal differentiated thyroid cancer either treated with definitive intent or untreated in active surveillance that has been stable for the past year prior to randomization.
3. Have active tumor bleeding or a high risk of bleeding (examples include but are not limited to radiographic evidence of major blood vessel invasion/infiltration or tumor demonstrates >90 degree abutment or encasement of a major vessel [carotid, jugular, bronchial artery] and/or exhibits other high-risk features such as arteriovenous fistula). Note: Minimal bleeding or oozing not considered high risk, in oral/oropharyngeal tumors, is permitted.
4. Has PD within 4 months of completion of curatively intended treatment for locoregionally advanced HNSCC.
5. Participants with any carcinomatous meningitis or leptomeningeal spread and those with uncontrolled or symptomatic CNS metastases. Note: Participants with previously treated brain metastases may participate provided they are asymptomatic (any neurologic symptoms have returned to baseline [participants may be receiving stable doses of anticonvulsants]), radiographically stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of study treatment), have no evidence of new or enlarging brain metastases, and are clinically stable off steroids for at least 2 weeks prior to initiation of study treatment.
6. Active autoimmune disease that has required systemic disease-modifying or immunosuppressive treatment within the last 2 years. (Note: Stable, medically managed autoimmune endocrinopathies are acceptable if participant otherwise meets entry criteria.)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Confirmed ORR, defined as the percentage of participants achieving confirmed CR or PR per RECIST 1.1 by investigator assessment.

Investigational products

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

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Glaxosmithkline Research & Development Limited

Sponsor organisation

Glaxosmithkline Research & Development Limited

Address

G S K House, 980 Great West Road 980 Great West Road

City

Brentford

Postcode

TW8 9GS

Country

United Kingdom

Scientific contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trials Call Center

Public contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trials Call Center

Third parties 23

Locations

12 EU/EEA countries · 70 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 230 files

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

Application history

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