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RecruitingInterventionalPhase 2

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)

NCT ID: NCT07098338Sponsor: AstraZenecaLast updated: 2026-05-27

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.

Detailed description

The master protocol will include 3 sub-studies, each focused on a specific disease population. * Sub-study 1 will investigate rilvegostomig± ramucirumab in 1L non-actionable genomic alterations (AGA) NSCLC with PD-L1 ≥50%. * Sub-study 2 will investigate rilvegostomig + ramucirumab in 1L non-actionable genomic alterations (AGA) NSCLC with PD-L1 1-49%. * Sub-study 3 will investigate Dato-DXd + ramucirumab ± rilvegostomig in 2/3L AGA+ Each sub-study may include 2 parts (unless stated in the individual sub study protocols): Part A: one or more Safety Run-in cohort(s), and Part B: one or more Dose Expansion cohort(s).

Arms & interventions

  • DrugRilvegostomig

    Rilvegostomig will be administered as IV infusion.

  • DrugRamucirumab

    Ramucirumab will be administered as IV infusion.

  • DrugDato-DXd

    Dato-DXd will be administered as IV infusion.

Outcome measures

Primary

  • Number of participants with adverse events (AE) and serious adverse events (SAE)

    To assess the safety and tolerability

    Time frame: Through study completion, an average of 3 years

  • Objective response rate (ORR)

    ORR is defined as the proportion of participants who have a confirmed CR (complete response) or confirmed PR (partial response) per RECIST 1.1

    Time frame: Through study completion, an average of 3 years

Secondary

  • Best Overall Response(BOR)

    Time frame: Through study completion, an average of 3 years

  • Change in Target Lesion Tumor Size

    Time frame: Through study completion, an average of 3 years

  • Progression free survival (PFS)

    Time frame: Through study completion, an average of 3 years

  • Disease Control Rate(DCR) at 12 Weeks

    Time frame: From Day 1 pre-dose to 12 weeks

  • Duration Of Response (DoR)

    Time frame: Through study completion, an average of 3 years

  • Overall Survival(OS)

    Time frame: Through study completion, an average of 3 years

  • Serum concentration

    Time frame: Through study completion, an average of 3 years

  • Maximum plasma drug concentration (Cmax)

    Time frame: Through study completion, an average of 3 years

  • Immunogenicity of study interventions in participants receiving treatment

    Time frame: Through study completion, an average of 3 years

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
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.

Study locations (6)

Research Site

Santa Monica, California, 90404

Not Yet Recruiting

Research Site

Santa Rosa, California, 95403

Not Yet Recruiting

Research Site

Atlanta, Georgia, 30318

Recruiting

Research Site

Baltimore, Maryland, 21231

Not Yet Recruiting

Research Site

Houston, Texas, 77090

Not Yet Recruiting

Research Site

Fairfax, Virginia, 22031

Recruiting
A Study of Novel Combinations in Non-Small Cell Lung Cancer (NSCLC) | Cancerify