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New drug combinations for advanced non-small cell lung cancer

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)

Phase 2 Interventional AstraZeneca · NCT07098338

This Phase II platform tests several combinations of targeted antibodies and antibody‑drug conjugates for adults with advanced or metastatic non‑small cell lung cancer, with treatment arms matched to PD‑L1 status and genomic findings.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment278 (estimated)
Ages18 Years and up
SexAll
SponsorAstraZeneca Industry-sponsored
Drugs / interventionschemotherapy, immunotherapy, ramucirumab
Locations64 sites (Santa Monica, California and 63 other locations)
Trial IDNCT07098338 on ClinicalTrials.gov

What this trial studies

This multi‑center, open‑label Phase II master protocol runs three sub‑studies that each test different drug combinations and include safety run‑in and dose‑expansion parts. Sub‑study 1 studies rilvegostomig ± ramucirumab in first‑line patients with PD‑L1 ≥50%, sub‑study 2 studies rilvegostomig + ramucirumab in first‑line patients with PD‑L1 1–49%, and sub‑study 3 studies Dato‑DXd + ramucirumab ± rilvegostomig in later‑line patients with actionable genomic alterations. The primary focus across sub‑studies is safety, tolerability, and preliminary anti‑tumor activity using standard imaging and RECIST 1.1 criteria. The protocol is planned at roughly 80 centers across about 10 countries and uses centrally defined eligibility and biomarker requirements to assign patients to the appropriate sub‑study.

Who should consider this trial

Good fit: Adults (≥18) with advanced or metastatic NSCLC, ECOG 0–1, measurable disease, adequate organ function, and the required PD‑L1 or actionable genomic status for the chosen sub‑study are the intended candidates.

Not a fit: People with poor performance status (ECOG >1), life expectancy under 12 weeks, uncontrolled comorbidities, or who lack the required PD‑L1 or genomic profile for a given sub‑study are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, these combinations could expand effective treatment options and improve response rates for people with advanced NSCLC across different PD‑L1 and genomic subgroups.

How similar studies have performed: Elements of this approach—antibody‑drug conjugates and VEGF‑pathway antibodies—have shown promising activity in NSCLC, while TIGIT‑targeted combinations remain earlier-stage and less proven when combined with these agents.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria for All Sub-studies:

* 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

Specific Inclusion Criteria for Sub-Study 1 and Sub-Study 2:

* 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)

Specific Inclusion Criteria for Sub-Study 3:

* Histologically or cytologically documented advanced or metastatic non-squamous NSCLC
* Documented positive AGA and had progressed on prior targeted therapy

Exclusion Criteria for All Sub-studies:

* 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.

Where this trial is running

Santa Monica, California and 63 other locations

+14 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 → Find more trials like this →
Conditions Non-Small Cell Lung CancerAntibody-Drug ConjugatesT-cell immunoreceptor with Ig and Immunoreceptor Tyrosine-based Inhibition Motif domainsProgrammed death-ligand 1
Last reviewed 2026-06-13 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.