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.

NCT05791097 | Withdrawn Phase 3 DMC FDA Drug

• 2 other identifiers: CWCD118A123012022-503098-12-00
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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%.

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

Outcome Measures

Primary Outcomes (2)

• 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)

  Time from date of randomization/start of treatment to the date of event defined as the first documented progression based on BIRC assessment as per RECIST 1.1 or death due to any cause in participants with PD-L1 expression in ≥1% of tumor cells, for participants in Arm A compared to Arm B

  Up to 30 months

• Overall survival (OS) in participants with PD-L1 expression in ≥1% of tumor cells (Arm A and B)

  Time from date of randomization/start of treatment to date of death due to any cause in participants with PD-L1 expression in ≥1% of tumor cells, for participants in Arm A compared to Arm B

  Up to 52 months

Secondary Outcomes (26)

• PFS based on BIRC assessment as per RECIST 1.1 in all participants regardless of PD-L1 status (Arm A and B)

  Up to 30 months

• OS in all participants regardless of PD-L1 status (Arm A and B)

  Up to 52 months

• Overall response rate (ORR) based in BIRC assessment as per RECIST 1.1 (Arm A and B)

  Up to 30 months

• Disease Control Rate (DCR) based in BIRC assessment as per RECIST 1.1 (Arm A and B)

  Up to 30 months

• Time to response (TTR) based in BIRC assessment as per RECIST 1.1 (Arm A and B)

  Up to 30 months

Study Arms (3)

Arm A: Ociperlimab + tislelizumab + chemotherapy

EXPERIMENTAL

Participants will receive ociperlimab in combination with tislelizumab and platinum-based doublet chemotherapy

Drug: Ociperlimab; Drug: Tislelizumab; Drug: Carboplatin; Drug: Cisplatin; Drug: Pemetrexed; Drug: Paclitaxel; Drug: Nab-paclitaxel

Arm B: Placebo + pembrolizumab + chemotherapy

ACTIVE COMPARATOR

Participants will receive ociperlimab placebo in combination with pembrolizumab and platinum-based doublet chemotherapy

Drug: Placebo; Drug: Pembrolizumab; Drug: Carboplatin; Drug: Cisplatin; Drug: Pemetrexed; Drug: Paclitaxel; Drug: Nab-paclitaxel

Arm C: Placebo + tislelizumab + chemotherapy

PLACEBO COMPARATOR

Participants will receive ociperlimab placebo in combination with tislelizumab and platinum-based doublet chemotherapy

Drug: Placebo; Drug: Tislelizumab; Drug: Carboplatin; Drug: Cisplatin; Drug: Pemetrexed; Drug: Paclitaxel; Drug: Nab-paclitaxel

Interventions

Ociperlimab DRUG

Ociperlimab is a monoclonal antibody formulated for intravenous infusion. 900 mg of ociperlimab will be administered on Day 1 of each 21-day cycle

Also known as: WCD118

Arm A: Ociperlimab + tislelizumab + chemotherapy

Placebo DRUG

Placebo infusions will consist of a sterile, normal saline solution. Placebo will be administered on Day 1 of each 21-day cycle

Arm B: Placebo + pembrolizumab + chemotherapy; Arm C: Placebo + tislelizumab + chemotherapy

Tislelizumab DRUG

Tislelizumab is a monoclonal antibody formulated for intravenous infusion. 200 mg of tislelizumab will be administered on Day 1 of each 21-day cycle

Also known as: VDT482

Arm A: Ociperlimab + tislelizumab + chemotherapy; Arm C: Placebo + tislelizumab + chemotherapy

Pembrolizumab DRUG

Pembrolizumab is a monoclonal antibody formulated for intravenous infusion. 200 mg of pembrolizumab will be administered on Day 1 of each 21-day cycle

Arm B: Placebo + pembrolizumab + chemotherapy

Carboplatin DRUG

Carboplatin is a chemotherapy agent formulated for intravenous infusion. Carboplatin will be administered (AUC 6 mg/mL\*min) on Day 1 of each 21-day cycle

Arm A: Ociperlimab + tislelizumab + chemotherapy; Arm B: Placebo + pembrolizumab + chemotherapy; Arm C: Placebo + tislelizumab + chemotherapy

Cisplatin DRUG

Cisplatin is a chemotherapy agent formulated for intravenous infusion. Cisplatin will be administered (75 mg/m\^2) on Day 1 of each 21-day cycle

Arm A: Ociperlimab + tislelizumab + chemotherapy; Arm B: Placebo + pembrolizumab + chemotherapy; Arm C: Placebo + tislelizumab + chemotherapy

Pemetrexed DRUG

Pemetrexed is a chemotherapy agent formulated for intravenous infusion. Pemetrexed will be administered (500 mg/m\^2) on Day 1 of each 21-day cycle

Arm A: Ociperlimab + tislelizumab + chemotherapy; Arm B: Placebo + pembrolizumab + chemotherapy; Arm C: Placebo + tislelizumab + chemotherapy

Paclitaxel DRUG

Paclitaxel is a chemotherapy agent formulated for intravenous infusion. Paclitaxel will be administered (200 mg/m\^2) on Day 1 of each 21-day cycle

Arm A: Ociperlimab + tislelizumab + chemotherapy; Arm B: Placebo + pembrolizumab + chemotherapy; Arm C: Placebo + tislelizumab + chemotherapy

Nab-paclitaxel DRUG

Nab-paclitaxel is a chemotherapy agent formulated for intravenous infusion. Nab-paclitaxel will be administered (100 mg/m\^2) on Day 1, 8 and 15 of each 21-day cycle

Arm A: Ociperlimab + tislelizumab + chemotherapy; Arm B: Placebo + pembrolizumab + chemotherapy; Arm C: Placebo + tislelizumab + chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

tislelizumab; pembrolizumab; Carboplatin; Cisplatin; Pemetrexed; Paclitaxel; 130-nm albumin-bound paclitaxel

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2023
• First Posted: March 30, 2023
• Study Start: July 28, 2023
• Primary Completion (Estimated): December 24, 2027
• Study Completion (Estimated): December 26, 2027
• Last Updated: July 24, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will share