A Platform Study in Non-Small Cell Lung Cancer (NSCLC)

Official title

A Phase Ib/II Open-Label, Multicentre Platform Study Evaluating Novel Combinations in Participants With Advanced or Metastatic Non-Small Cell Lung Cancer

Overview

The purpose of this study is to assess the safety and efficacy of multiple study interventions including novel-novel combinations or novel agents in combination with standard therapy for the treatment of metastatic NSCLC.

Detailed description

This is a multicentre, open-label study to evaluate the safety and efficacy of various combinations of study interventions in participants with advanced or metastatic NSCLC (mNSCLC).

The study will include a sub-study (sub-study 2) focused on a specific treatment that may include 2 parts -

1. Part A consisting of one of more safety run-in cohorts to evaluate 2 or more dose levels to identify the recommended Phase 2 dose (RP2D) unless RP2D has been established then Part A will not be required; and 2. Part B consisting of one or more expansion cohorts.

The originally planned Sub-study 1 was withdrawn (cancelled) and will not be conducted.

Sub-study 2 will evaluate the safety, tolerability, and anti-tumour activity of rilvegostomig plus standard of care (SoC) platinum-based chemotherapy, with or without ramucirumab.

Interventions

• Drug Rilvegostomig
  Rilvegostomig will be administered as an intravenous (IV) infusion.
• Drug Cisplatin
  Cisplatin will be administered as SoC as an IV infusion.
• Drug Carboplatin
  Carboplatin will be administered as SoC as an IV infusion.
• Drug Pemetrexed
  Pemetrexed will be administered as SoC as an IV infusion.
• Drug Paclitaxel
  Paclitaxel will be administered as SoC as an IV infusion.
• Drug Nab-paclitaxel
  Nab-paclitaxel will be administered as SoC as an IV infusion.
• Drug Ramucirumab
  Ramucirumab will be administered as an IV infusion.

Primary outcome measures

• Part A and Part B: Number of participants with adverse events (AEs) and serious adverse events (SAEs) [Time frame: Approximately 46 months]
• Part A: Number of partcipants with dose limiting toxicity (DLT) [Time frame: Approximately 46 months]
• Part B: Objective response (OR) [Time frame: Approximately 46 months]

Secondary outcome measures (12)

• Part A: Objective response (OR) [Time frame: Approximately 46 months]
• Part A and Part B: Duration of response (DOR) [Time frame: Approximately 46 months]
• Part A and Part B: Time to response (TTR) [Time frame: Approximately 46 months]
• Part A and Part B: Disease control (DC) [Time frame: Approximately 46 months]
• Part A and Part B: Progression free survival (PFS) [Time frame: Approximately 46 months]
• Part A and Part B: Progression free survival at 6 months (PFS6) [Time frame: From Day 1 pre-dose to 6 months]
• Part A and Part B: Progression free survival at 12 months (PFS12) [Time frame: From Day 1 pre-dose to 12 months]
• Part A and Part B: Overall survival (OS) [Time frame: Approximately 46 months]
• Part A and Part B: Overall survival at 12 months (OS12) [Time frame: From Day 1 pre-dose to 12 months]
• Part A and Part B: Serum concentration [Time frame: Approximately 46 months]
• Part A and Part B: Maximum plasma drug concentration (Cmax) [Time frame: Approximately 46 months]
• Part A and Part B: Area under plasma concentration-time curve from time 0 to last quantifiable concentration (AUClast) [Time frame: Approximately 46 months]

Eligibility criteria

Inclusion criteria

• Participants with confirmed squamous or non-squamous NSCLC with a current Stage IV mNSCLC.
• Provision of acceptable archival tumour tissue (or fresh tumour tissue biopsy if archival tumour tissue is not available and if clinically feasible) is mandatory at screening.
• Measurable disease as defined by at least one lesion that can be accurately measured at baseline as ≥ 10 mm at the longest diameter.
• Minimum life expectancy of 12 weeks in the opinion of the investigator.
• Adequate organ and marrow function.
• Contraceptive use by male or female participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Adequate organ and marrow function.

Inclusion Criteria for Sub Study 2:

• Programmed death-ligand 1 (PD-L1) tumour proportion score (TPS) ≥ 1% (per local report).
• Adequate coagulation and urinalysis.
• Minimum body weight of 30 kg.

Exclusion criteria

• Participants with epidermal growth factor receptor mutations, anaplastic lymphoma receptor fusions or any other known genomic alteration for which targeted therapy is approved in the first line per local standard of care.
• Presence of small cell and neuroendocrine histology components.
• Any severe or uncontrolled systemic diseases, including uncontrolled hypertension, and active bleeding diseases, ongoing or active known infection; interstitial lung disease/pneumonitis (of any grade); unstable and/or symptomatic venous thromboembolism, serious chronic gastrointestinal conditions associated with diarrhoea, active non-infectious skin disease or substance abuse.
• Has had a prior stem cell, bone marrow, allogenic tissue, or solid organ transplant.
• Has an active autoimmune disease that has required systemic treatment in the past 5 years.
• History of clinically significant arrhythmia, cardiomyopathy of any aetiology or symptomatic congestive heart failure.
• History of another primary malignancy except for malignancy treated with curative intent with no known active disease ≥ 2 years before the first dose of study intervention or presence of small cell and neuroendocrine histology components.
• Persistent toxicities (common terminology criteria for adverse events \[CTCAE\] ≥ Grade 2) caused by previous anti-cancer therapy, excluding alopecia.
• Spinal cord compression or symptomatic brain metastases.
• Treatment with any other anti-cancer agents or immunosuppressive medication.
• Palliative radiotherapy with a limited field of radiation within 2 weeks or with a wide field of radiation or to more than 30% of the bone marrow within 4 weeks, prior to the first dose of study intervention.

Exclusion Criteria for Sub Study 2:

• Known active hepatitis A.
• Acute hepatitis B infection (anti-hepatitis B core antibody \[HBc\] immunoglobulin M \[IgM\] positive) or chronic hepatitis B infection with HBV DNA ≥ 2000 IU/mL.
• Active hepatitis C infection (anti-HCV positive with HCV RNA detectable) or anti- HCV positive with HCV RNA undetectable for less than 12 weeks following treatment for HCV.
• Known human immunodeficiency virus (HIV) infection that is not well controlled.
• Evidence of Grade ≥ 1 central nervous system (CNS) haemorrhage.
• Uncontrolled arterial hypertension ≥ 150 mm Hg (systolic) and/or ≥ 100 mm Hg (diastolic).
• Has radiologically documented evidence of major blood vessel invasion or encasement by cancer, or major airway invasion by cancer or intra-tumour cavitation.
• Has experienced any arterial thrombotic event, a Grade ≥ 3 bleeding event or has gross haemoptysis.
• Has significant bleeding disorders, serious or nonhealing wound, ulcer or clinically relevant congestive heart failure.
• Has a bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection.
• Has cirrhosis at a level of Child-Pugh B (or worse), or cirrhosis (any degree) and a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis.
• Prior systemic therapy received for advanced or mNSCLC.
• Prior exposure to an anti-T-cell immunoreceptor with Ig and Immunoreceptor Tyrosine-based Inhibition Motif domains (TIGIT) therapy or immune-oncology agent such as anti-programmed cell death protein 1 (PD-1), anti-PD-L1, or anti-cytotoxic T-lymphocyte associated antigen 4 (CTLA-4), or any other anti-cancer therapy targeting immune-regulatory receptors or mechanisms.
• Chronic therapy with antiplatelet agents.
• Prior exposure to anti-vascular endothelial growth factor (VEGF) therapy.
• Medical contraindication to protocol-specified platinum doublet regimens or ramucirumab.
• Known allergy or hypersensitivity to rilvegostomig or any of the excipients of rilvegostomig, cisplatin, carboplatin, paclitaxel or nab-paclitaxel or pemetrexed or ramucirumab.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

China · 12 centers

• Research Site — Chengdu
• Research Site — Chongqing
• Research Site — Deyang
• Research Site — Fuzhou
• Research Site — Guangzhou
• Research Site — Jinan
• Research Site — Shanghai
• Research Site — Shanghai
• … and 4 more centers

United States · 10 centers

• Research Site — Phoenix
• Research Site — Santa Rosa
• Research Site — Jacksonville
• Research Site — Baltimore
• Research Site — Detroit
• Research Site — Rochester
• Research Site — Cleveland
• Research Site — Providence
• … and 2 more centers

Spain · 9 centers

Center list to be confirmed — check the primary protocol.

Japan · 8 centers

• Research Site — Bunkyō City
• Research Site — Bunkyō City
• Research Site — Kashiwa
• Research Site — Kurume-shi
• Research Site — Kyoto
• Research Site — Niigata
• Research Site — Shinjuku-ku
• Research Site — Toyoake-shi

Brazil · 7 centers

• Research Site — Barretos
• Research Site — Fortaleza
• Research Site — Natal
• Research Site — Pelotas
• Research Site — Porto Alegre
• Research Site — São Paulo
• Research Site — São Paulo

France · 7 centers

• Research Site — Bordeaux
• Research Site — Dijon
• Research Site — Limoges
• Research Site — Marseille
• Research Site — Nantes
• Research Site — Nice
• Research Site — Paris

Georgia · 5 centers

• Research Site — Batumi
• Research Site — Tbilisi
• Research Site — Tbilisi
• Research Site — Tbilisi
• Research Site — Tbilisi

Germany · 5 centers

• Research Site — München
• Research Site — Münster
• Research Site — Oldenburg
• Research Site — Regensburg
• Research Site — Würzburg

Italy · 5 centers

• Research Site — Milan
• Research Site — Milan
• Research Site — Orbassano
• Research Site — Pavia
• Research Site — Roma

South Korea · 5 centers

• Research Site — Seongbuk-Gu
• Research Site — Seoul
• Research Site — Seoul
• … and 2 more centers

Thailand · 5 centers

Center list to be confirmed — check the primary protocol.

Malaysia · 4 centers

• Research Site — Kuala Lumpur
• Research Site — Kuala Selangor
• Research Site — Kuching
• Research Site — Singapore

Turkey (Türkiye) · 4 centers

Center list to be confirmed — check the primary protocol.

Belgium · 3 centers

• Research Site — Anderlecht
• Research Site — Hasselt
• Research Site — Leuven

Netherlands · 3 centers

• Research Site — Amsterdam
• Research Site — Groningen
• Research Site — Leiden

Poland · 3 centers

• Research Site — Koszalin
• Research Site — Lodz
• Research Site — Olsztyn

Serbia · 3 centers

• Research Site — Belgrade
• Research Site — Kragujevac
• Research Site — Niš

Taiwan · 3 centers

Center list to be confirmed — check the primary protocol.

Moldova · 1 center

• Research Site — Chisinau

Peru · 1 center

• Research Site — Lima

Identifiers

NCT: NCT06996782 · D702KC00001 · 2024-519786-22

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗