A study to evaluate novel immunotherapy combinations in participants with advanced non-small cell lung cancer (NSCLC)

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]

Trial duration

10 Jul 2024 → ongoing

Decision date (initial)

2024-06-24

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Servier Portugal-Especialidaded Farmaceûticas, LDA · ADIR France · Laboratorios Servier, S. L

External identifiers

EU CT number

2023-508730-34-00

ClinicalTrials.gov

NCT06162572

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Pharmacokinetic, Safety, Efficacy, Pharmacodynamic

Part A (combination therapy safety lead-in): To evaluate the safety and tolerability of each combination arm and to confirm the recommended dose for expansion (RDE)
Part B (Randomized dose expansion): To evaluate the efficacy of each combination arm compared with the cemiplimab (control) arm

Secondary objectives 8

1. Part A (combination therapy safety lead-in): To evaluate the efficacy of each combination arm
2. Part A (combination therapy safety lead-in): To characterize the pharmacokinetic (PK) profile of S095018, S095024 and S095029 when administered in combination with cemiplimab
3. Part A (combination therapy safety lead-in): To evaluate the immunogenicity of S095018, S095024 and S095029
4. Part B (Randomized dose expansion): To evaluate the safety and tolerability of each combination arm compared with the cemiplimab (control) arm
5. Part B (Randomized dose expansion): To further assess the efficacy of each combination arm, compared with the cemiplimab (control) arm, using RECIST v1.1 and overall survival
6. Part B (Randomized dose expansion): To evaluate the efficacy of each combination arm, compared with the cemiplimab (control) arm, using iRECIST
7. Part B (Randomized dose expansion): To further characterize the PK profile of S095018, S095024 and S095029 when administered in combination with cemiplimab
8. Part B (Randomized dose expansion): To further evaluate the immunogenicity of S095018, S095024 and S095029

Conditions and MedDRA coding

Non-small cell lung cancer (NSCLC): - Locally advanced NSCLC where participants are not candidates for surgical resection and/or definitive chemoradiation, or - Metastatic NSCLC

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Histologically (squamous or non-squamous) or cytologically documented locally advanced NSCLC not eligible for surgical resection and/or definitive chemoradiation, or metastatic NSCLC
2. No prior systemic treatment for locally advanced or metastatic NSCLC
3. High tumor cell PD-L1 expression [Tumor Proportion Score (TPS) ≥50%] based on documented status as determined by an approved test
4. Adult participants (must be ≥18 years of age or according to local requirement)
5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
6. Measurable disease as determintaed by RECIST v1.1

Exclusion criteria 15

1. Tumors harboring driver mutations/genetic aberrations for which targeted therapies are approved as frontline treatment (e.g., EGFR mutation, ALK fusion oncogene, ROS1 aberrations)
2. Systemic chronic steroid therapy (>10mg/d prednisone or equivalent)
3. Clinical significant infection, as assessed by the investigators.
4. Pregnant or breast-feeding (lactating) women
5. Participants with a history of allogeneic organ transplantation (e.g., stem cell or solid organ transplant)
6. Any medical condition that would in the investigator's judgement prevent the participant's participation in the clinical study
7. Prior immune checkpoint inhibitor therapy.
8. Active brain metastases
9. Participants with active and uncontrolled hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
10. Uncontrolled HIV infection. Participants with HIV who have controlled infection (undetectable viral load and CD4 count above 350 either spontaneously or on a stable antiviral regimen) are allowed to enroll
11. Active, known or suspected autoimmune disease or immune deficiency
12. History of hypersensitivity reactions to any ingredient of the investigational medicinal product (IMP) and other monoclonal antibody (mAbs) and/or their excipients
13. History of interstitial lung disease, idiopathic pulmonary fibrosis, drug-induced pneumonitis, idiopathic pneumonitis or active pneumonitis ≥ grade 2
14. History of inflammatory bowel disease or colitis ≥ grade 2
15. History of hemophagocytic lymphohistiocytosis

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Part A (combination therapy safety lead-in): Incidence and severity of dose-limiting toxicities (DLTs) during the first 2 cycles of combination treatment
2. Part A (combination therapy safety lead-in): Incidence and severity of adverse events (AEs), serious adverse events (SAEs), changes from baseline in laboratory values/laboratory abnormalities, electrocardiograms (ECGs) and vital signs according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v5.0)
3. Part A (combination therapy safety lead-in): AEs leading to dose interruption, modification, delays, and permanent treatment discontinuation
4. Part B (Randomized dose expansion): Objective Response (OR) per investigator assessment using RECIST v1.1

Secondary endpoints 8

1. Part A (combination therapy safety lead-in): Objective response (OR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and immune Response Evaluation Criteria in Solid Tumors (iRECIST) as assessed by the investigator
2. Part B (Randomized dose expansion): Objective response (OR) according to immune Response Evaluation Criteria in Solid Tumors (iRECIST) as assessed by the investigator
3. Part A (combination therapy safety lead-in) and Part B (Randomized dose expansion): best overall response (BOR), duration of response (DoR), disease control (DC), 6-month durable response (6-month DR) and Progression-Free Survival (PFS), according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and immune RECIST (iRECIST) as assessed by the investigator
4. Part A (combination therapy safety lead-in) and Part B (Randomized dose expansion): Overall survival (OS)
5. Part A (combination therapy safety lead-in) and Part B (Randomized dose expansion): Plasma or serum concentrations of S095018, S095024 or S095029
6. Part A (combination therapy safety lead-in) and Part B (Randomized dose expansion): Incidence and titer of anti-drug antiodies (ADA) directed against S095018, S095024 or S095029
7. Part B (Randomized dose expansion): Incidence and severity of adverse events (AEs), serious adverse events (SAEs), changes in laboratory values/laboratory abnormalities, ECGs and vital signs according to NCI-CTCAE v5.0
8. Part B (Randomized dose expansion): AEs leading to dose interruption, modification, delays, and permanent treatment discontinuation

Investigational products

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

Test 4

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 · 34 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 7 · Art. 38 CTR

Results and documents

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

Documents 53 files

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

Application history

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