Clinical trial NCT05791097: Study of Efficacy and Safety of Ociperlimab in Combination With Tislelizumab and Platinum-based Doublet Chemotherapy as First-line Treatment for Participants With Locally Advanced or Metastatic NSCLC.
Official title: AdvanTIG-306: A Randomized, Double-blind, Placebo-controlled, Phase III Study Evaluating the Efficacy and Safety of Ociperlimab (WCD118/BGB-A1217) Combined With Tislelizumab (VDT482/BGB-A317) Plus Platinum-based Doublet Chemotherapy Versus Placebo Combined With Pembrolizumab Plus Platinum-based Doublet Chemotherapy as First-line Therapy for Participants With Locally Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Non-small Cell Lung Cancer (NSCLC)
Keywords: AdvanTIG-306
ociperlimab
tislelizumab
pembrolizumab
carboplatin
cisplatin
paclitaxel
nab-paclitaxel
pemetrexed
squamous
non-squamous
non-small cell lung cancer
NSCLC
PD-L1
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2023-03-30
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary scientific question of interest is whether the addition of ociperlimab to platinum-based chemotherapy and tislelizumab improve progression-free survival (PFS) or overall survival (OS) compared to pembrolizumab and platinum-based chemotherapy as first-line therapy for participants with locally advanced or metastatic squamous or non-squamous NSCLC with PD-L1 expression of ≥1%.

Detailed description: This is a randomized, double-blind, placebo controlled, multicenter, phase III study evaluating the efficacy and safety of ociperlimab in combination with tislelizumab and platinum-based doublet chemotherapy as first-line treatment for participants with locally advanced or metastatic NSCLC without actionable driver mutations.

Participants will receive study treatment every three weeks and will continue to receive it until RECIST 1.1 disease progression as determined by Investigator and confirmed by BIRC, unacceptable toxicity that precludes further treatment, treatment is discontinued at the discretion of the Investigator or participant, participant withdrawal of consent, pregnancy, lost to follow-up, or death.

Eligibility criteria: Key Inclusion Criteria:

* Histologically confirmed locally advanced (stage IIIb/IIIc not eligible for definitive chemoradiation, radiation or surgery) or metastatic (stage IV) NSCLC (according to AJCC: Cancer Staging Manual, 8th edition) participants with no previous systemic treatment for advanced disease.
* Known PD-L1 status determined, prior to study randomization
* At least one measurable lesion as defined by RECIST 1.1 according to local radiology assessment at screening.
* ECOG performance status ≤1.

Key Exclusion Criteria:

* Active autoimmune diseases requiring treatment with steroids or immunosuppressors in the past 2 years prior to randomization.
* History of severe hypersensitivity reaction or any contraindication to ociperlimab, tislelizumab, pembrolizumab (or any other monoclonal antibodies), platinum containing drugs, nab-paclitaxel, paclitaxel, pemetrexed or any known excipients of these drugs.
* Participants with known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
* Participants with documented epidermal growth factor receptor (EGFR) sensitizing mutations, and/or ALK rearrangement assessed as part of the patients's standard of care by a validated test, as per local regulations will be excluded from the study.
* Participants with other known druggable molecular drivers (any histology) such as BRAF V600, KRASG12C, MET exon 14 mutations, NTRK, RET or ROS-1 rearrangement diagnosed per local tests who might be candidates for alternative targeted therapies as applicable per local regulations and treatment guidelines are excluded.

Other inclusion/exclusion criteria may apply

Primary outcomes:
measure: Progression-free survival (PFS) based on Blinded Independent Review Committee (BIRC) assessment as per RECIST 1.1 in participants with PD-L1 expression in ≥1% of tumor cells (Arm A and B)
timeFrame: Up to 30 months
measure: Overall survival (OS) in participants with PD-L1 expression in ≥1% of tumor cells (Arm A and B)
timeFrame: Up to 52 months
Secondary outcomes:
measure: PFS based on BIRC assessment as per RECIST 1.1 in all participants regardless of PD-L1 status (Arm A and B)
timeFrame: Up to 30 months
measure: OS in all participants regardless of PD-L1 status (Arm A and B)
timeFrame: Up to 52 months
measure: Overall response rate (ORR) based in BIRC assessment as per RECIST 1.1 (Arm A and B)
timeFrame: Up to 30 months
measure: Disease Control Rate (DCR) based in BIRC assessment as per RECIST 1.1 (Arm A and B)
timeFrame: Up to 30 months
measure: Time to response (TTR) based in BIRC assessment as per RECIST 1.1 (Arm A and B)
timeFrame: Up to 30 months
measure: Duration of response (DOR) based in BIRC assessment as per RECIST 1.1 (Arm A and B)
timeFrame: Up to 30 months
measure: ORR based in BIRC assessment as per RECIST 1.1 (Arm A and C)
timeFrame: Up to 30 months
measure: DCR based in BIRC assessment as per RECIST 1.1 (Arm A and C)
timeFrame: Up to 30 months
measure: TTR based in BIRC assessment as per RECIST 1.1 (Arm A and C)
timeFrame: Up to 30 months
measure: DOR based in BIRC assessment as per RECIST 1.1 (Arm A and C)
timeFrame: Up to 30 months
measure: PFS based on BIRC assessment as per RECIST 1.1 (Arm A and C)
timeFrame: Up to 30 months
measure: Pharmacokinetic (PK) parameter: Area under the serum concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) of ociperlimab and tislelizumab
timeFrame: Up to 30 months
measure: PK parameter: Maximum concentration (Cmax) of ociperlimab and tislelizumab
timeFrame: Up to 30 months
measure: PK parameter: Time to reach maximum concentration (Tmax) of ociperlimab and tislelizumab
timeFrame: Up to 30 months
measure: PK parameter: Lowest serum concentration reached before the next dose is administered (Ctrough) of ociperlimab and tislelizumab
timeFrame: Up to 30 months
measure: PK parameter: AUC calculated at the end of the dosing interval (AUCtau)of ociperlimab and tislelizumab
timeFrame: Up to 30 months
measure: Immunogenicity: Anti-drug antibodies (ADA) prevalence at baseline of ociperlimab and tislelizumab
timeFrame: Baseline
measure: Immunogenicity: ADA incidence following treatment with ociperlimab and tislelizumab
timeFrame: Up to 30 months
measure: Time to definitive 10-point deterioration in physical and role functioning on the EORTC QLQ-C30 questionnaire
timeFrame: Up to 30 months
measure: Time to definitive 10-point deterioration in symptom scores for chest pain, cough and dyspnea on the EORTC QLQ-LC13 questionnaire
timeFrame: Up to 30 months
measure: Time to confirmed 10-point deterioration in physical and role functioning on the EORTC QLQ-C30 questionnaire
timeFrame: Up to 30 months
measure: Time to confirmed 10-point deterioration in symptom scores for chest pain, cough and dyspnea on the EORTC QLQ-LC13 questionnaire
timeFrame: Up to 30 months
measure: Time to definitive 10-point deterioration in global health status/quality of life, shortness of breath and pain on the EORTC QLQ-C30 questionnaire
timeFrame: Up to 30 months
measure: Utility scores of the EQ-5D-5L
timeFrame: Up to 30 months
measure: Progression-free survival deferred (PFS2)
timeFrame: Up to 30 months
measure: Time to definitive deterioration of the ECOG performance status
timeFrame: Up to 30 months
Other outcomes:
Locations:
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: