A study to evaluate the safety and the activity of S095029 as a part of combination therapy in advanced gastroesophageal junction/gastric cancers

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Institut De Recherches Internationales Servier IRIS

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Diseases [C] - Digestive System Diseases [C06]

Trial duration

23 May 2024 → ongoing

Decision date (initial)

2024-05-10

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Laboratorios Servier, S. L. · ADIR France

External identifiers

EU CT number

2023-507995-33-00

ClinicalTrials.gov

NCT06116136

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Others, Efficacy, Safety, Pharmacokinetic, Dose response

Phase 1b (safety lead in part):
To evaluate the safety and tolerability of the combination and to identify the recommended Phase 2 dose (RP2D) of S095029 in combination therapy.

Phase 2:
- To evaluate the antitumor activity of S095029 in combination therapy
- To evaluate the safety and tolerability profile of S095029 in combination therapy

Secondary objectives 7

1. Phase 1b (safety lead in part): To evaluate the antitumor activity of S095029 in the combination therapy as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and immune RECIST (iRECIST) criteria.
2. Phase 1b (safety lead in part): To characterize the pharmacokinetic (PK) profile of S095029 in combination therapy.
3. Phase 1b (safety lead in part): To evaluate the immunogenicity of S095029 in combination therapy.
4. Phase 2: To further assess the antitumor activity of S095029 with defined combination therapy through duration of responses, survival, clinical benefit.
5. Phase 2: To evaluate the antitumor activity of S095029 with defined combination therapy as per iRECIST criteria.
6. Phase 2: To characterize the pharmacokinetic (PK) profile of S095029 in combination therapy.
7. Phase 2: To evaluate the immunogenicity of S095029 in combination therapy.

Conditions and MedDRA coding

MSI-H/dMMR Gastric cancer

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

1. Participants must have a histologically or cytologically confirmed diagnosis of a locally advanced and unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma.
2. Participants’ tumor must have an MSI-H/dMMR status according to institutional guidelines and/or according to the College of American Pathologists, determined at any time prior to enrolment. This status may be documented in a report in the participant’s medical history or the MSI-H/dMMR status may be documented by testing archival tumor tissue or tissue from a newly collected tumor biopsy (if no appropriate archived specimen is available).

Exclusion criteria 5

1. Has received prior therapy with any checkpoint inhibitor (anti-PD-1, anti-programmed cell death ligand 1 (PDL1), anti-CTLA4).
2. Has received more than one previous line of treatment in the locally advanced and unresectable or metastatic setting. Previous treatment line may include trastuzumab and chemotherapy, or doublet/triplet chemotherapy regimens. Note: participants who have received only one cycle of chemotherapy prior to determination of their tumor’s MSI-H status, and who have not yet been treated with an anti-PD-1/L1 agent are not considered to have had one prior line of treatment. Previous treatment with chemotherapy in the neoadjuvant or adjuvant setting is permitted and is not counted as a previous line of therapy for the purpose of determining a patient’s eligibility.
3. Participants who have received prior systemic anti-cancer therapy including investigational agents within 4 weeks (shorter interval, at least 5 half-lives, for kinase inhibitors or other short half-life drugs), prior to first study treatment.
4. Prior radiotherapy if completed less than 2 weeks before first study treatment or have had a history of radiation pneumonitis. Participants who have not recovered from all radiation-related toxicities and require corticosteroids. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
5. Major surgery less than 4 weeks prior to the first study treatment or participants who have not recovered from the side effects of the surgery.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 5

1. Phase 1b and Phase 2: Incidence of dose-limiting toxicities (DLTs).
2. Phase 1b and Phase 2: Frequency and severity of adverse events (AEs) and laboratory abnormalities according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v5.0).
3. Phase 1b and Phase 2: Incidence of AEs leading to dose interruption, modification, delays and permanent treatment discontinuation.
4. Phase 1b and Phase 2: Change from baseline to the end of the study in safety laboratory values and vital signs.
5. Phase 2: Objective response (OR) per investigator assessment using RECIST v1.1.

Secondary endpoints 6

1. Phase 1b: Objective response (OR), duration of response (DoR), progression-free survival (PFS), and disease control (DC) according to RECIST v1.1 and iRECIST as assessed by investigator.
2. Phase 1b and Phase 2: Overall survival (OS) per investigator assessment.
3. Phase 1b and Phase 2: Serum concentrations of S095029
4. Phase 1b and Phase 2: Concentration of potential antibodies directed against S095029.
5. Phase 2: DoR, PFS, and DC according to RECIST v1.1 as assessed by investigator.
6. Phase 2: OR, DoR, PFS, and DC according to iRECIST criteria as per investigator assessment.

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Institut De Recherches Internationales Servier IRIS

Sponsor organisation

Institut De Recherches Internationales Servier IRIS

Address

22 Route 128

City

Gif Sur Yvette

Postcode

91190

Country

France

Scientific contact point

Organisation

Institut De Recherches Internationales Servier IRIS

Contact name

Clinical Studies Department

Public contact point

Organisation

Institut De Recherches Internationales Servier IRIS

Contact name

Clinical Studies Department

Third parties 9

Locations

7 EU/EEA countries · 27 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 85 files

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

Application history

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