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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT06162572




Registration number
NCT06162572
Ethics application status
Date submitted
29/11/2023
Date registered
8/12/2023
Date last updated
13/05/2024

Titles & IDs
Public title
Phase 1b/2 Platform Study of Select Immunotherapy Combinations in Participants With Advanced Non-small Cell Lung Cancer (NSCLC)
Scientific title
A Phase 1b/2, Multicenter, Open-label Platform Study of Select Immunotherapy Combinations in Adult Participants With Previously Untreated Advanced Non-small Cell Lung Cancer (NSCLC) With High PD-L1 Expression
Secondary ID [1] 0 0
SPLFIO-174
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-small Cell Lung Cancer (NSCLC) 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - S095018
Treatment: Drugs - S095024
Treatment: Drugs - S095029
Treatment: Drugs - S095018 Recommended Dose Expansion (RDE)
Treatment: Drugs - S095024 RDE
Treatment: Drugs - S095029 RDE
Treatment: Drugs - Cemiplimab

Experimental: S095018 (anti-TIM3 antibody) in combination with cemiplimab - Part A: Combination-therapy safety lead-in

Experimental: S095024 (anti-CD73 antibody) in combination with cemiplimab - Part A: Combination-therapy safety lead-in

Experimental: S095029 (anti-NKG2A antibody) in combination with cemiplimab - Part A: Combination-therapy safety lead-in

Experimental: S095018 (anti-TIM3 antibody) RDE in combination with cemiplimab - Part B: Randomized dose expansion

Experimental: S095024 (anti-CD73 antibody) RDE in combination with cemiplimab - Part B: Randomized dose expansion

Experimental: S095029 (anti-NKG2A antibody) RDE in combination with cemiplimab - Part B: Randomized dose expansion

Active Comparator: Cemiplimab (control arm) - Part B: Randomized dose expansion


Treatment: Drugs: S095018
Via IV infusion on Day 1 of each 21-day cycle

Treatment: Drugs: S095024
Via IV infusion on Day 1 of each 21-day cycle

Treatment: Drugs: S095029
Via IV infusion on Day 1 of each 21-day cycle

Treatment: Drugs: S095018 Recommended Dose Expansion (RDE)
Via IV infusion on Day 1 of each 21-day cycle

Treatment: Drugs: S095024 RDE
Via IV infusion on Day 1 of each 21-day cycle

Treatment: Drugs: S095029 RDE
Via IV infusion on Day 1 of each 21-day cycle

Treatment: Drugs: Cemiplimab
350 mg via IV infusion on Day 1 of each 21-day cycle
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence and severity of dose-limiting toxicities (DLTs) during the first 2 cycles of combination treatment
Timepoint [1] 0 0
Through the end of the Cycle 2 (each cycle is 21 days)
Primary outcome [2] 0 0
Incidence and severity of adverse events (AEs)
Timepoint [2] 0 0
From the signed informed consent form (ICF) to 30 days after the last dose
Primary outcome [3] 0 0
Incidence and severity of serious adverse events (SAEs)
Timepoint [3] 0 0
From the signed ICF to 120 days after the last dose
Primary outcome [4] 0 0
Adverse Events (AEs) Leading to Dose Interruption, Modification, or Delays
Timepoint [4] 0 0
From signed ICF through treatment discontinuation (up to 108 weeks of treatment)
Primary outcome [5] 0 0
Adverse Events (AEs) Leading to Permanent Treatment Discontinuation
Timepoint [5] 0 0
From signed ICF through treatment discontinuation (up to 108 weeks of treatment)
Primary outcome [6] 0 0
Objective Response (OR)
Timepoint [6] 0 0
Until study termination (approximately 2 years)
Secondary outcome [1] 0 0
Objective Response (OR)
Timepoint [1] 0 0
Until study termination (approximately 3 years)
Secondary outcome [2] 0 0
Best Overall Response (BOR)
Timepoint [2] 0 0
Until study termination (approximately 3 years)
Secondary outcome [3] 0 0
Duration of Response (DoR)
Timepoint [3] 0 0
Until study termination (approximately 3 years)
Secondary outcome [4] 0 0
Disease Control (DC)
Timepoint [4] 0 0
Until study termination (approximately 3 years)
Secondary outcome [5] 0 0
6-month Durable Response (6-month DR)
Timepoint [5] 0 0
Until study termination (approximately 3 years)
Secondary outcome [6] 0 0
Progression-Free Survival (PFS)
Timepoint [6] 0 0
Until study termination (approximately 3 years)
Secondary outcome [7] 0 0
Plasma or serum concentration of S095018
Timepoint [7] 0 0
From first dose to 30 days after the last dose
Secondary outcome [8] 0 0
Plasma or serum concentration of S095024
Timepoint [8] 0 0
From first dose to 30 days after the last dose
Secondary outcome [9] 0 0
Plasma or serum concentration of S095029
Timepoint [9] 0 0
From first dose to 30 days after the last dose
Secondary outcome [10] 0 0
Incidence and titer of anti-drug antibodies (ADA) directed against S095018
Timepoint [10] 0 0
From screening to 90 days after the last dose
Secondary outcome [11] 0 0
Incidence and titer of anti-drug antibodies (ADA) directed against S095024
Timepoint [11] 0 0
From screening to 90 days after the last dose
Secondary outcome [12] 0 0
Incidence and titer of anti-drug antibodies (ADA) directed against S095029
Timepoint [12] 0 0
From screening to 90 days after the last dose
Secondary outcome [13] 0 0
Incidence and severity of adverse events (AEs)
Timepoint [13] 0 0
From signed ICF to 30 days after the last dose
Secondary outcome [14] 0 0
Incidence and severity of serious adverse events (SAEs)
Timepoint [14] 0 0
From signed ICF to 120 days after the last dose
Secondary outcome [15] 0 0
Adverse Events (AEs) Leading to Dose Interruption, Modification, or Delays
Timepoint [15] 0 0
From signed ICF through treatment discontinuation (up to 108 weeks of treatment)
Secondary outcome [16] 0 0
Adverse Events (AEs) Leading to Permanent Treatment Discontinuation
Timepoint [16] 0 0
From signed ICF through treatment discontinuation (up to 108 weeks of treatment)

Eligibility
Key inclusion criteria
- Adult patient aged = 18 years

- Written informed consent

- Histologically (squamous or non-squamous) or cytologically documented locally advanced
NSCLC not eligible for surgical resection and/or definitive chemoradiation, or
metastatic NSCLC

- No prior systemic treatment for locally advanced or metastatic NSCLC

- High tumor cell PD-L1 expression [Tumor Proportion Score (TPS) =50%] based on
documented status as determined by an approved test

- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

- Measurable disease as determined by RECIST v1.1
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Tumors harboring driver mutations/genetic aberrations for which targeted therapies are
approved as frontline treatment (e.g. EGFR mutation, ALK fusion oncogene, ROS1
aberrations)

- Prior immune checkpoint inhibitor therapy

- Active brain metastases

- Participants with active and uncontrolled hepatitis B virus (HBV) or hepatitis C virus
(HCV) infection

- 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

- Active, known or suspected autoimmune disease or immune deficiency

- History of hypersensitivity reactions to any ingredient of the investigational
medicinal product (IMP) and other monoclonal antibody (mAbs) and/or their excipients

- History of interstitial lung disease, idiopathic pulmonary fibrosis, drug-induced
pneumonitis, idiopathic pneumonitis or active pneumonitis = grade 2

- History of inflammatory bowel disease or colitis = grade 2

- Systemic chronic steroid therapy (>10mg/d prednisone or equivalent)

- Active infection, including infection requiring systemic antibiotic therapy

- Pregnant or breast-feeding (lactating) women

- Participants with a history of allogeneic organ transplantation (e.g., stem cell or
solid organ transplant)

- Any medical condition that would in the investigator's judgement prevent the
participant's participation in the clinical study

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
7/06/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/07/2027
Actual
Sample size
Target
176
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Albury Wodonga Regional Cancer Centre; Border Medical Oncology Research Unit - Albury
Recruitment hospital [2] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [3] 0 0
Sunshine Hospital - St Albans
Recruitment postcode(s) [1] 0 0
2640 - Albury
Recruitment postcode(s) [2] 0 0
5042 - Bedford Park
Recruitment postcode(s) [3] 0 0
3021 - St Albans
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Ohio
Country [2] 0 0
United States of America
State/province [2] 0 0
Virginia
Country [3] 0 0
Hong Kong
State/province [3] 0 0
Hong Kong

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Servier Bio-Innovation LLC
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Institut de Recherches Internationales Servier
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/Industry
Name [2] 0 0
Regeneron Pharmaceuticals
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This is a Phase 1b/2 study evaluating the anti-PD1 antibody, cemiplimab, in combination with
either S095018 (anti-TIM3 antibody), S095024 (anti-CD73 antibody), or S095029 (anti-NKG2A
antibody) in adult participants with previously untreated advanced/metastatic non-small cell
lung cancer (NSCLC) with high PD-L1 expression. The study includes two parts: part A, the
combination-therapy safety lead-in phase to determine the recommended dose for expansion
(RDE) for S095018, S095024, and S095029 in combination with cemiplimab and part B, the
randomized dose expansion phase to assess the efficacy of S095018, S095024, or S095029 in
combination with cemiplimab. Study treatment will be administered for a maximum of 108 weeks,
or until confirmed disease progression per iRECIST and/ or until meeting other treatment
discontinuation criteria.
Trial website
https://clinicaltrials.gov/ct2/show/NCT06162572
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Institut de Recherches Internationales Servier (I.R.I.S.), Clinical Studies Department
Address 0 0
Country 0 0
Phone 0 0
+33 1 55 72 60 00
Fax 0 0
Email 0 0
scientificinformation@servier.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT06162572