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Platform of new drug combinations for advanced non-small cell lung cancer

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

PHASE1; PHASE2 · AstraZeneca · NCT06996782

This will test rilvegostomig given with platinum-based chemotherapy, with or without ramucirumab, in people with advanced or metastatic non-small cell lung cancer whose tumors have PD-L1 TPS ≥1%.

Quick facts

PhasePHASE1; PHASE2
Study typeInterventional
Enrollment152 (estimated)
Ages18 Years and up
SexAll
SponsorAstraZeneca (industry)
Drugs / interventionsramucirumab, radiation, chemotherapy
Locations104 sites (Phoenix, Arizona and 103 other locations)
Trial IDNCT06996782 on ClinicalTrials.gov

What this trial studies

This is a multicenter, open-label platform that tests multiple combination regimens in participants with advanced or metastatic NSCLC. Sub-study 2 includes a Part A safety run-in to identify a recommended Phase 2 dose (unless already established) followed by Part B expansion cohorts to further evaluate activity. The sub-study specifically examines rilvegostomig plus standard platinum-based chemotherapy, with or without ramucirumab, and requires archival or fresh tumor tissue and measurable disease at baseline. Key eligibility includes PD-L1 TPS ≥1% (for this sub-study), adequate organ function, and a minimum life expectancy as judged by the investigator.

Who should consider this trial

Good fit: Ideal candidates are adults with confirmed stage IV (advanced or metastatic) NSCLC, measurable disease, adequate organ and marrow function, available tumor tissue, and PD-L1 TPS ≥1%.

Not a fit: Patients who lack PD-L1 expression below the required threshold, have poor organ function, or otherwise fail eligibility (for example poor performance status) are unlikely to benefit from this sub-study.

Why it matters

Potential benefit: If successful, the combination could improve tumor response rates or extend control of disease for some patients with metastatic NSCLC.

How similar studies have performed: Combining checkpoint-targeting agents with chemotherapy has improved outcomes in NSCLC, though TIGIT-targeted approaches are relatively new and have shown mixed but promising results in early trials.

Eligibility criteria

Show full inclusion / exclusion 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.

Where this trial is running

Phoenix, Arizona and 103 other locations

+54 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Advanced or Metastatic Non-small Cell Lung Cancer, Checkpoint inhibitor, Platinum-based chemotherapy, T-cell immunoreceptor with lg and Immunoreceptor Tyrosine-based Inhibition Motif domains, Programmed death-ligand 1

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.