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

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT06062420

Collaborator

iTeos Therapeutics (Industry)

360

Enrollment

122

Locations

Arms

41.5

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary purpose of the study is to evaluate the antitumor activity and safety of novel immunotherapy combinations compared with dostarlimab in participants with Programmed death ligand 1 (PD-L1) positive Recurrent/Metastatic (R/M) Head and Neck Squamous Cell Carcinoma (HNSCC).

Condition or Disease	Intervention/Treatment	Phase
Neoplasms, Head and Neck	Drug: Dostarlimab Drug: Belrestotug Drug: GSK6097608	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

360 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 2, Randomized, Open-label, Platform Study Using a Master Protocol to Evaluate Novel Immunotherapy Combinations as First-Line Treatment in Participants With Recurrent/Metastatic PD-L1 Positive Squamous Cell Carcinoma of the Head and Neck

Anticipated Study Start Date :

Oct 4, 2023

Anticipated Primary Completion Date :

Mar 19, 2027

Anticipated Study Completion Date :

Mar 19, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dostarlimab Monotherapy	Drug: Dostarlimab Dostarlimab will be administered.
Experimental: Sub study 1: Dostarlimab and Belrestotug	Drug: Dostarlimab Dostarlimab will be administered. Drug: Belrestotug Belrestotug will be administered.
Experimental: Sub study 2: Dostarlimab and GSK6097608	Drug: Dostarlimab Dostarlimab will be administered. Drug: GSK6097608 GSK6097608 will be administered.
Experimental: Sub study 3: Dosarlimab and Belrestotug and GSK6097608	Drug: Dostarlimab Dostarlimab will be administered. Drug: Belrestotug Belrestotug will be administered. Drug: GSK6097608 GSK6097608 will be administered.

Outcome Measures

Primary Outcome Measures

Confirmed Objective Response Rate (ORR) compared between Sub studies and Dostarlimab monotherapy [Up to approximately 24 months]
Confirmed ORR is defined as the percentage of participants achieving confirmed Complete Response (CR) or Partial Response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by investigator assessment.

Secondary Outcome Measures

Overall Survival (OS) compared between Sub studies and Dostarlimab monotherapy [Up to approximately 24 months]
OS is defined as the time from the date of randomization to the date of death due to any cause.
Duration of Response (DOR) compared between Sub studies and Dostarlimab monotherapy [Up to approximately 24 months]
DOR per RECIST 1.1 by investigator assessment, defined as the time from the date of first documented objective response (CR or PR) to the date of first documented Disease progression (PD) or death due to any cause, whichever comes first.
Progression Free Survival (PFS) compared between Sub studies and Dostarlimab monotherapy [Up to approximately 24 months]
PFS per RECIST 1.1 by investigator assessment, defined as the time from the date of randomization to the date of first documented PD or death due to any cause, whichever comes first.
Disease Control Rate (DCR) compared between Sub studies and Dostarlimab monotherapy [Up to approximately 24 months]
DCR is defined as the percentage of participants achieving CR or PR, or Stable disease (SD) greater than or equal to (≥) 6 months, per RECIST 1.1 by investigator assessment.
Rate of Circulating Tumor Deoxyribonucleic Acid (ctDNA) Molecular Response [Up to approximately 24 months]
The rate of ctDNA molecular response, is defined as the percentage of participants achieving a ≥50% decrease in ctDNA level compared to baseline, measured by plasma ctDNA assessment
Confirmed Objective Response Rate (ORR) compared between Sub study3 and Sub studies 1 and 2 [Up to approximately 24 months]
Confirmed ORR is defined as the percentage of participants achieving confirmed CR or PR per RECIST version 1.1 by investigator assessment.
Overall Survival (OS) compared between Sub study 3 and Sub studies 1 and 2 [Up to approximately 24 months]
OS is defined as the time from the date of randomization to the date of death due to any cause.
Duration of Response (DOR) compared between Sub study 3 and Sub studies 1 and 2 [Up to approximately 24 months]
DOR per RECIST v 1.1 by investigator assessment, defined as the time from the date of first documented objective response (CR or PR) to the date of first documented PD or death due to any cause, whichever comes first.
Progression Free Survival (PFS) compared between Sub study 3 and Sub studies 1 and 2 [Up to approximately 24 months]
PFS per RECIST 1.1 by investigator assessment, defined as the time from the date of randomization to the date of first documented PD or death due to any cause, whichever comes first.
DCR compared between sub study 3 and Sub studies 1 and 2 [Up to approximately 24 months]
DCR is defined as the percentage of participants achieving CR or PR, or Stable disease (SD) ≥ 6 months, per RECIST v1.1 by investigator assessment.
Number of Participants with Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAE) and Adverse Events of Special Interest (AESI) [Up to approximately 24 months]
Number of Participants with TEAEs or SAEs leading to dose modifications or study intervention discontinuation [Up to approximately 24 months]
Number of Participants with Clinically Significant Findings in Physical examination, Vital signs, Electrocardiogram (ECG), Echocardiogram (ECHO) and Laboratory test parameters [Up to approximately 24 months]
Number of Participants with Anti-Drug Antibodies (ADA) against Dostarlimab [Up to approximately 24 months]
Number of Participants with Anti-Drug Antibodies (ADA) against Belrestotug [Up to approximately 24 months]
Number of Participants with Anti-Drug Antibodies (ADA) against GSK6097608 [Up to approximately 24 months]
Maximum Concentration (Cmax) and Minimum Concentration (Cmin) of Dostarlimab [Up to approximately 24 months]
Cmax and Cmin of Belrestotug [Up to approximately 24 months]
Cmax and Cmin of GSK6097608 [Up to approximately 24 months]
Correlation of molecular response to clinical activity parameter [Up to approximately 24 months]
Correlation will be assessed by comparing clinical activity parameter (confirmed ORR), between ctDNA molecular responders and non-responders within each treatment arm. Confirmed ORR is defined as the percentage of participants achieving confirmed Complete Response (CR) or Partial Response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by investigator assessment.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Have histologically or cytologically-confirmed R/M HNSCC that is 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 6 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)
Has measurable (target) disease based on RECIST 1.1 as determined by the investigator.
Has an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1
Provides a tumor tissue sample obtained at the time of or after the initial diagnosis of R/M HNSCC. Although a fresh tumor tissue sample obtained within 90 days of screening is highly preferred, an archival tumor specimen (≤2 years old) is acceptable. 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.
Has tumor Programmed death ligand 1 (PD-L1) expression
If the primary tumor site is oropharyngeal carcinoma, the participant must have Human papillomavirus (HPV) results

Exclusion Criteria:

Has received prior therapy with any immune checkpoint inhibitors, including antibodies or drugs targeting Programmed death protein 1 (PD-1), PD-L1, Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine based inhibitory motif domains (TIGIT), Cluster of differentiation (CD) 96, or other immune checkpoint pathways.
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.
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).
Has PD within 4 months of completion of curatively intended treatment for locoregionally advanced HNSCC
Participants with any carcinomatous meningitis or leptomeningeal spread and those with uncontrolled or symptomatic Central Nervous System (CNS) metastases
Active autoimmune disease that has required systemic disease-modifying or immunosuppressive treatment within the last 2 years. (Stable, medically managed autoimmune endocrinopathies are acceptable if participant otherwise meets entry criteria.)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	New Haven	Connecticut	United States	06511
2	GSK Investigational Site	Boston	Massachusetts	United States	02215
3	GSK Investigational Site	Saint Louis	Missouri	United States	63021
4	GSK Investigational Site	Omaha	Nebraska	United States	68198
5	GSK Investigational Site	Columbus	Ohio	United States	43210-1240
6	GSK Investigational Site	Milwaukee	Wisconsin	United States	53226
7	GSK Investigational Site	Capital Federal	Buenos Aires	Argentina	C1426ANZ
8	GSK Investigational Site	Ciudad Autonoma de Buenos Aires	Buenos Aires	Argentina	C1181ACH
9	GSK Investigational Site	Ciudad Autónoma de Buenos Aires	Buenos Aires	Argentina	C1426ABP
10	GSK Investigational Site	Ciudad Autónoma de Buenos Aires		Argentina	C1417DTN
11	GSK Investigational Site	Cordoba		Argentina	5000
12	GSK Investigational Site	Mendoza		Argentina	M5500AYB
13	GSK Investigational Site	San Juan		Argentina	5400
14	GSK Investigational Site	Santa Fe		Argentina	3000
15	GSK Investigational Site	Santo Andre	Sao Paulo	Brazil	09060-650
16	GSK Investigational Site	São Paulo		Brazil	01221-020
17	GSK Investigational Site	São Paulo		Brazil	01246-000
18	GSK Investigational Site	São Paulo		Brazil	04014-002
19	GSK Investigational Site	Calgary	Alberta	Canada	T2N 4N2
20	GSK Investigational Site	Edmonton	Alberta	Canada	T6G 1Z2
21	GSK Investigational Site	Toronto	Ontario	Canada	M4N 3M5
22	GSK Investigational Site	Toronto	Ontario	Canada	M5G 2M9
23	GSK Investigational Site	Montreal	Quebec	Canada	H3T 1E2
24	GSK Investigational Site	Herlev		Denmark
25	GSK Investigational Site	Turku		Finland	20520
26	GSK Investigational Site	Bordeaux Cedex		France	33075
27	GSK Investigational Site	Caen Cedex 5		France	14075
28	GSK Investigational Site	Marseille		France	13005
29	GSK Investigational Site	Paris		France	75005
30	GSK Investigational Site	Rouen		France	76038
31	GSK Investigational Site	Saint Herblain		France	44805
32	GSK Investigational Site	Villejuif Cedex		France	94805
33	GSK Investigational Site	Ulm	Baden-Wuerttemberg	Germany	89075
34	GSK Investigational Site	Regensburg	Bayern	Germany	93053
35	GSK Investigational Site	Frankfurt	Hessen	Germany	60488
36	GSK Investigational Site	Giessen	Hessen	Germany	35392
37	GSK Investigational Site	Aachen	Nordrhein-Westfalen	Germany	52074
38	GSK Investigational Site	Essen	Nordrhein-Westfalen	Germany	45122
39	GSK Investigational Site	Leipzig	Sachsen	Germany	04103
40	GSK Investigational Site	Berlin		Germany	12200
41	GSK Investigational Site	Hamburg		Germany	20246
42	GSK Investigational Site	Athens		Greece
43	GSK Investigational Site	Haidari, Athens		Greece	12462
44	GSK Investigational Site	Thessaloniki		Greece	54622
45	GSK Investigational Site	Thessaloniki		Greece	55236
46	GSK Investigational Site	Gyor		Hungary	9024
47	GSK Investigational Site	Kecskemét		Hungary	6000
48	GSK Investigational Site	Nyíregyháza		Hungary	4400
49	GSK Investigational Site	Pécs		Hungary	7624
50	GSK Investigational Site	Szolnok		Hungary	5000
51	GSK Investigational Site	Napoli	Campania	Italy	80131
52	GSK Investigational Site	Bologna	Emilia-Romagna	Italy	40139
53	GSK Investigational Site	Roma	Lazio	Italy	00144
54	GSK Investigational Site	Roma	Lazio	Italy	00168
55	GSK Investigational Site	Genova	Liguria	Italy	16132
56	GSK Investigational Site	Milano	Lombardia	Italy	20133
57	GSK Investigational Site	Rozzano (MI)	Lombardia	Italy	20089
58	GSK Investigational Site	Novara	Piemonte	Italy	28100
59	GSK Investigational Site	Bari	Puglia	Italy	70124
60	GSK Investigational Site	Firenze	Toscana	Italy	50134
61	GSK Investigational Site	Padova	Veneto	Italy	35128
62	GSK Investigational Site	Aichi		Japan	464-8681
63	GSK Investigational Site	Chiba		Japan	277-8577
64	GSK Investigational Site	Hyogo		Japan	650-0017
65	GSK Investigational Site	Osaka		Japan	541-8567
66	GSK Investigational Site	Saitama		Japan	350-1298
67	GSK Investigational Site	Shizuoka		Japan	411-8777
68	GSK Investigational Site	Tokyo		Japan	104-0045
69	GSK Investigational Site	Daegu-si		Korea, Republic of	42601
70	GSK Investigational Site	Seongnam-si, Gyeonggi-do		Korea, Republic of	13620
71	GSK Investigational Site	Seoul		Korea, Republic of	03722
72	GSK Investigational Site	Seoul		Korea, Republic of	138-736
73	GSK Investigational Site	Oslo		Norway	0379
74	GSK Investigational Site	Bielsko-Biala		Poland	43-300
75	GSK Investigational Site	Gliwice		Poland	44-102
76	GSK Investigational Site	Koszalin		Poland	75-581
77	GSK Investigational Site	Krakow		Poland	31-826
78	GSK Investigational Site	Poznan		Poland	60-569
79	GSK Investigational Site	Przemysl		Poland	37-700
80	GSK Investigational Site	Siedlce		Poland	08-110
81	GSK Investigational Site	Warszawa		Poland	04-141
82	GSK Investigational Site	Almada		Portugal	2801-951
83	GSK Investigational Site	Lisboa		Portugal	1649-035
84	GSK Investigational Site	Porto		Portugal	4099-001
85	GSK Investigational Site	Porto		Portugal	4200-072
86	GSK Investigational Site	Pitesti	Arges	Romania	110283
87	GSK Investigational Site	Brasov		Romania	500152
88	GSK Investigational Site	Brasov		Romania	500283
89	GSK Investigational Site	Bucharest		Romania	020142
90	GSK Investigational Site	Bucharest		Romania	030171
91	GSK Investigational Site	Bucharest		Romania
92	GSK Investigational Site	Bucuresti		Romania	021389
93	GSK Investigational Site	Bucuresti		Romania	30463
94	GSK Investigational Site	Craiova		Romania	200094
95	GSK Investigational Site	Craiova		Romania	200542
96	GSK Investigational Site	Floresti		Romania	407280
97	GSK Investigational Site	Iasi		Romania	700483
98	GSK Investigational Site	Oradea		Romania	410469
99	GSK Investigational Site	Suceava		Romania	720214
100	GSK Investigational Site	Barcelona		Spain	08023
101	GSK Investigational Site	Barcelona		Spain	08035
102	GSK Investigational Site	Barcelona		Spain	08907
103	GSK Investigational Site	Jaén		Spain	23007
104	GSK Investigational Site	Madrid		Spain	28010
105	GSK Investigational Site	Madrid		Spain	28034
106	GSK Investigational Site	Madrid		Spain	28040
107	GSK Investigational Site	Madrid		Spain	28041
108	GSK Investigational Site	Pozuelo De Alarcón/Madrid		Spain	28223
109	GSK Investigational Site	Salamanca		Spain	37007
110	GSK Investigational Site	Santander		Spain	39008
111	GSK Investigational Site	Valencia		Spain	46009
112	GSK Investigational Site	Zaragoza		Spain	50009
113	GSK Investigational Site	Stockholm		Sweden	SE-171 76
114	GSK Investigational Site	Uppsala		Sweden	SE- 75 185
115	GSK Investigational Site	Changhua		Taiwan	500
116	GSK Investigational Site	Tainan		Taiwan	704
117	GSK Investigational Site	Taipei City		Taiwan	11217
118	GSK Investigational Site	Taipei		Taiwan	10002
119	GSK Investigational Site	Ankara		Turkey	06100
120	GSK Investigational Site	Antalya		Turkey	07020
121	GSK Investigational Site	Istanbul		Turkey	34662
122	GSK Investigational Site	İzmir		Turkey	35040