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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT06162572
Ethics application status
Date submitted
29/11/2023
Date registered
8/12/2023

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
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
31/08/2024
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
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
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Kansas
Country [3] 0 0
United States of America
State/province [3] 0 0
Michigan
Country [4] 0 0
United States of America
State/province [4] 0 0
Nevada
Country [5] 0 0
United States of America
State/province [5] 0 0
Ohio
Country [6] 0 0
United States of America
State/province [6] 0 0
Virginia
Country [7] 0 0
Argentina
State/province [7] 0 0
Buenos Aires
Country [8] 0 0
Argentina
State/province [8] 0 0
Tucumán
Country [9] 0 0
Austria
State/province [9] 0 0
Linz
Country [10] 0 0
Austria
State/province [10] 0 0
St. Poelten
Country [11] 0 0
Austria
State/province [11] 0 0
Wien
Country [12] 0 0
Belgium
State/province [12] 0 0
Hasselt
Country [13] 0 0
Belgium
State/province [13] 0 0
Leuven
Country [14] 0 0
Brazil
State/province [14] 0 0
Barretos
Country [15] 0 0
Brazil
State/province [15] 0 0
Chapecó
Country [16] 0 0
Brazil
State/province [16] 0 0
Curitiba
Country [17] 0 0
Brazil
State/province [17] 0 0
Ijuí
Country [18] 0 0
Brazil
State/province [18] 0 0
Natal
Country [19] 0 0
Brazil
State/province [19] 0 0
Porto Alegre
Country [20] 0 0
Brazil
State/province [20] 0 0
Rio De Janeiro
Country [21] 0 0
Brazil
State/province [21] 0 0
São Paulo
Country [22] 0 0
France
State/province [22] 0 0
Dijon
Country [23] 0 0
France
State/province [23] 0 0
Grenoble
Country [24] 0 0
France
State/province [24] 0 0
Marseille
Country [25] 0 0
France
State/province [25] 0 0
Saint-Herblain
Country [26] 0 0
France
State/province [26] 0 0
Villejuif
Country [27] 0 0
Hong Kong
State/province [27] 0 0
Hong Kong
Country [28] 0 0
Hungary
State/province [28] 0 0
Farkasgyepu
Country [29] 0 0
Hungary
State/province [29] 0 0
Gyöngyös
Country [30] 0 0
Hungary
State/province [30] 0 0
Pécs
Country [31] 0 0
Italy
State/province [31] 0 0
Aviano
Country [32] 0 0
Italy
State/province [32] 0 0
Meldola
Country [33] 0 0
Italy
State/province [33] 0 0
Milano
Country [34] 0 0
Italy
State/province [34] 0 0
Napoli
Country [35] 0 0
Italy
State/province [35] 0 0
Perugia
Country [36] 0 0
Italy
State/province [36] 0 0
Roma
Country [37] 0 0
Italy
State/province [37] 0 0
Rozzano
Country [38] 0 0
Korea, Republic of
State/province [38] 0 0
Busan
Country [39] 0 0
Korea, Republic of
State/province [39] 0 0
Cheongju-si
Country [40] 0 0
Korea, Republic of
State/province [40] 0 0
Incheon
Country [41] 0 0
Korea, Republic of
State/province [41] 0 0
Seoul
Country [42] 0 0
Romania
State/province [42] 0 0
Cluj-Napoca
Country [43] 0 0
Romania
State/province [43] 0 0
Craiova
Country [44] 0 0
Romania
State/province [44] 0 0
Otopeni
Country [45] 0 0
Romania
State/province [45] 0 0
Ploiesti
Country [46] 0 0
Spain
State/province [46] 0 0
Barcelona
Country [47] 0 0
Spain
State/province [47] 0 0
Madrid
Country [48] 0 0
Spain
State/province [48] 0 0
Málaga
Country [49] 0 0
Spain
State/province [49] 0 0
Pamplona
Country [50] 0 0
Spain
State/province [50] 0 0
Sevilla
Country [51] 0 0
Spain
State/province [51] 0 0
Valencia
Country [52] 0 0
Taiwan
State/province [52] 0 0
Taipei
Country [53] 0 0
United Kingdom
State/province [53] 0 0
London
Country [54] 0 0
United Kingdom
State/province [54] 0 0
Manchester

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
Trial website
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
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data.

Access can be requested for all interventional clinical studies:

* used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).
* where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope.

In addition, access can be requested for all interventional clinical studies in patients:

* sponsored by Servier
* with a first patient enrolled as of 1 January 2004 onwards
* for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
After Marketing Authorization in EEA or US if the study is used for the approval.
Available to whom?
Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://clinicaltrials.servier.com/


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT06162572