A Study of Novel Combinations in Non-Small Cell Lung Cancer (NSCLC)
An Open-Label, Multi-Drug, Multi-Centre, Phase II Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Antitumour Activity of Novel Combinations in Participants With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (LIBRA)
AstraZeneca
278 participants
Aug 7, 2025
INTERVENTIONAL
Summary
This is a Phase II, multi-center, open-label platform study evaluating novel combination treatment options in participants with locally advanced or metastatic NSCLC. The study will consist of several sub-studies, each evaluating the safety, tolerability, and preliminary antitumour activity of various treatment combinations. This study will be conducted in approximately 80 centers globally across 10 countries.
Eligibility
Inclusion Criteria11
- Participant must be ≥ 18 years of age at the time of signing the ICF
- WHO/ECOG performance status of 0 or 1
- At least 1 lesion that qualifies as a RECIST 1.1 Target Lesion (TL) at baseline.
- Adequate bone marrow and organ function
- Life expectancy ≥ 12 weeks
- Provision of acceptable tumour tissue
- Histologically or cytologically documented advanced or metastatic NSCLC
- PD-L1 TC ≥ 1% (TC≥ 50% for sub-study 1, 1-49% for sub-study 2)
- Absence of sensitizing EGFR mutations or ALK rearrangements. No known other Actionable Genomic Alterations(AGAs)
- Histologically or cytologically documented advanced or metastatic non-squamous NSCLC
- Documented positive AGA and had progressed on prior targeted therapy
Exclusion Criteria13
- As judged by the investigator, any severe or uncontrolled systemic diseases, in the investigator's opinion, makes it undesirable for the participant to participate in the study or that would jeopardise compliance with the protocol
- Active or prior documented autoimmune or inflammatory disorders
- Persistent toxicities (CTCAE Grade ≥ 2) (NCI CTCAE v5.0) caused by previous anti cancer therapy, excluding alopecia.
- Spinal cord compression or leptomeningeal carcinomatosis for sub-study 1 and sub-study 2. Unstable spinal cord compression for sub-study 3
- Unstable brain metastases
- History of another primary malignancy.
- Active infection, including TB and infections with HIV, HBV (verified by known positive HBsAg result), HCV.
- Uncontrolled or significant cardiac disease
- Receipt of prior systemic chemotherapy/chemoradiation/immunotherapy for advanced NSCLC for sub-study 1 and sub-study 2.
- Prior exposure to immune-mediated therapy
- History of uncontrolled hypertension, and active bleeding diseases, and high risks of bleeding and disorders of coagulation
- Any concurrent anti-cancer treatment.
- Receipt of live, attenuated vaccine within 30 days prior to the first dose of study intervention.
Interventions
Rilvegostomig will be administered as IV infusion.
Ramucirumab will be administered as IV infusion.
Dato-DXd will be administered as IV infusion.
Locations(63)
View Full Details on ClinicalTrials.gov
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NCT07098338