A Study of Novel Combinations in Non-Small Cell Lung Cancer (NSCLC) - LIBRA

Study identifier:D6187C00001

ClinicalTrials.gov identifier:NCT07098338

EudraCT identifier:N/A

CTIS identifier:N/A

Will Be Recruiting

Official Title

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)

Medical condition

Non-small Cell Lung Cancer

Phase

Phase 2

Healthy volunteers

Study drug

Rilvegostomig, Ramucirumab, Dato-DXd

Sex

All

Estimated Enrollment

278

Study type

Interventional

Age

18 Years - n/a

Date

Study Start Date: 08 Aug 2025

Estimated Primary Completion Date: 08 Sept 2026

Estimated Study Completion Date: 09 Apr 2029

Study design

Allocation: Non-randomized
Endpoint Classification: -
Intervention Model: Sequential Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Jul 2025 by AstraZeneca

Collaborators

Inclusion and 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.

No locations available

Arms	Assigned Interventions
Experimental: Sub-study 1, investigate rilvegostomig± ramucirumab in 1L non-AGA NSCLC with PD-L1 ≥50% Participants will receive rilvegostomig ± ramucirumab until RECIST 1.1-defined radiological progression as assessed by the investigator, unacceptable toxicity, withdrawal of consent, or other discontinuation criterion	Drug: Rilvegostomig Rilvegostomig will be administered as IV infusion. Other Name: AZD2936 Drug: Ramucirumab Ramucirumab will be administered as IV infusion. Other Name: Cyramza
Experimental: Sub-study 2, investigate rilvegostomig + ramucirumab in 1L non-AGA NSCLC with PD-L1 1-49% Participants will receive rilvegostomig + ramucirumab until RECIST 1.1-defined radiological progression as assessed by the investigator, unacceptable toxicity, withdrawal of consent, or other discontinuation criterion	Drug: Rilvegostomig Rilvegostomig will be administered as IV infusion. Other Name: AZD2936 Drug: Ramucirumab Ramucirumab will be administered as IV infusion. Other Name: Cyramza
Experimental: Sub-study 3, investigate Dato-DXd + ramucirumab ± rilvegostomig in 2L AGA+ NSCLC Participants will receive Dato-DXd + ramucirumab ± rilvegostomig until RECIST 1.1-defined radiological progression as assessed by the investigator, unacceptable toxicity, withdrawal of consent, or other discontinuation criterion	Drug: Rilvegostomig Rilvegostomig will be administered as IV infusion. Other Name: AZD2936 Drug: Ramucirumab Ramucirumab will be administered as IV infusion. Other Name: Cyramza Drug: Dato-DXd Dato-DXd will be administered as IV infusion. Other Name: DS-1062

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]