Rilvegostomig: Rilvegostomig will be administered as an intravenous (IV) infusion.
Cisplatin: Cisplatin will be administered as SoC as an IV infusion.
Carboplatin: Carboplatin will be administered as SoC as an IV infusion.
Pemetrexed: Pemetrexed will be administered as SoC as an IV infusion.
Paclitaxel: Paclitaxel will be administered as SoC as an IV infusion.
Nab-paclitaxel: Nab-paclitaxel will be administered as SoC as an IV infusion.
Ramucirumab: Ramucirumab will be administered as an IV infusion.
Study summary
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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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.
Primary outcome measure(s)
Part A and Part B: Number of participants with adverse events (AEs) and serious adverse events (SAEs) — Approximately 46 months To assess the safety and tolerability and determine RP2D of the combination of novel anti-cancer agents.
Part A: Number of partcipants with dose limiting toxicity (DLT) — Approximately 46 months To assess the safety and tolerability and determine RP2D of the combination of novel anti-cancer agents.
Part B: Objective response (OR) — Approximately 46 months The OR is defined as a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR).
Trial sites (103)
Facility
City
Region
Status
Research Site
Phoenix
Arizona
Recruiting
Research Site
Santa Rosa
California
Recruiting
Research Site
Jacksonville
Florida
Recruiting
Research Site
Baltimore
Maryland
Recruiting
Research Site
Detroit
Michigan
Not Yet Recruiting
Research Site
Rochester
Minnesota
Recruiting
Research Site
Cleveland
Ohio
Recruiting
Research Site
Providence
Rhode Island
Recruiting
Research Site
Providence
Rhode Island
Withdrawn
Research Site
Tyler
Texas
Recruiting
Research Site
Anderlecht
Belgium
Not Yet Recruiting
Research Site
Hasselt
Belgium
Not Yet Recruiting
Research Site
Leuven
Belgium
Not Yet Recruiting
Research Site
Barretos
Brazil
Not Yet Recruiting
Research Site
Fortaleza
Brazil
Not Yet Recruiting
Research Site
Natal
Brazil
Not Yet Recruiting
Research Site
Pelotas
Brazil
Not Yet Recruiting
Research Site
Porto Alegre
Brazil
Not Yet Recruiting
Research Site
São Paulo
Brazil
Not Yet Recruiting
Research Site
São Paulo
Brazil
Not Yet Recruiting
Research Site
Chengdu
China
Not Yet Recruiting
Research Site
Chongqing
China
Not Yet Recruiting
Research Site
Deyang
China
Not Yet Recruiting
Research Site
Fuzhou
China
Not Yet Recruiting
Research Site
Guangzhou
China
Not Yet Recruiting
Research Site
Jinan
China
Recruiting
Research Site
Shanghai
China
Recruiting
Research Site
Shanghai
China
Not Yet Recruiting
Research Site
Shenyang
China
Not Yet Recruiting
Research Site
Shenzhen
China
Not Yet Recruiting
Research Site
Wuhan
China
Not Yet Recruiting
Research Site
Wuhan
China
Not Yet Recruiting
Research Site
Bordeaux
France
Not Yet Recruiting
Research Site
Dijon
France
Not Yet Recruiting
Research Site
Limoges
France
Not Yet Recruiting
Research Site
Marseille
France
Not Yet Recruiting
Research Site
Nantes
France
Not Yet Recruiting
Research Site
Nice
France
Not Yet Recruiting
Research Site
Paris
France
Not Yet Recruiting
Research Site
Batumi
Georgia
Recruiting
+ 63 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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