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

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)

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.

Study Overview

• Status: Recruiting
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Dato-DXd; Drug: Rilvegostomig; Drug: Ramucirumab

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).

• Study Type: Interventional
• Enrollment (Estimated): 278
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• Australia
  • Heidelberg, Australia, 3084
    • Not yet recruiting
    • Research Site
  • Nedlands, Australia, 6009
    • Not yet recruiting
    • Research Site
  • Woodville, Australia, 5011
    • Not yet recruiting
    • Research Site
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Not yet recruiting
      • Research Site
• China
  • Changsha, China, 410013
    • Recruiting
    • Research Site
  • Chengdu, China, 610041
    • Recruiting
    • Research Site
  • Deyang, China, 618000
    • Recruiting
    • Research Site
  • Dongguan, China, 523059
    • Recruiting
    • Research Site
  • Fuzhou, China, 350014
    • Withdrawn
    • Research Site
  • Guangzhou, China, 510080
    • Recruiting
    • Research Site
  • Guangzhou, China, 510100
    • Recruiting
    • Research Site
  • Hangzhou, China, 310014
    • Recruiting
    • Research Site
  • Hefei, China, 230022
    • Recruiting
    • Research Site
  • Linyi, China, 276001
    • Recruiting
    • Research Site
  • Mianyang, China, 621000
    • Recruiting
    • Research Site
  • Nanchang, China, 330006
    • Recruiting
    • Research Site
  • Nanchang, China, 330000
    • Recruiting
    • Research Site
  • Shantou, China
    • Recruiting
    • Research Site
  • Shenyang, China, 110042
    • Recruiting
    • Research Site
  • Wuhan, China, 430022
    • Recruiting
    • Research Site
  • Zhengzhou, China, 450000
    • Recruiting
    • Research Site
  • Zhengzhou, China, 450008
    • Recruiting
    • Research Site
  • Zhuhai, China, 519000
    • Recruiting
    • Research Site
• France
  • Avignon, France, 84902
    • Not yet recruiting
    • Research Site
  • Paris, France, 75005
    • Not yet recruiting
    • Research Site
  • Rennes, France, 35000
    • Not yet recruiting
    • Research Site
  • Saint-Herblain, France, 44805
    • Not yet recruiting
    • Research Site
  • Suresnes, France, 92150
    • Not yet recruiting
    • Research Site
• Italy
  • Aviano, Italy, 33081
    • Not yet recruiting
    • Research Site
  • Catania, Italy, 95123
    • Not yet recruiting
    • Research Site
  • Meldola, Italy, 47014
    • Not yet recruiting
    • Research Site
  • Milan, Italy, 20141
    • Not yet recruiting
    • Research Site
  • Milan, Italy, 35128
    • Not yet recruiting
    • Research Site
  • Orbassano, Italy, 10043
    • Not yet recruiting
    • Research Site
  • Roma, Italy, 00144
    • Not yet recruiting
    • Research Site
  • Rozzano, Italy, 20089
    • Not yet recruiting
    • Research Site
• Japan
  • Bunkyō City, Japan, 113-8677
    • Recruiting
    • Research Site
  • Fukuyama-shi, Japan, 722-0001
    • Recruiting
    • Research Site
  • Kobe, Japan, 650-0047
    • Recruiting
    • Research Site
  • Kurume-shi, Japan, 830-0011
    • Recruiting
    • Research Site
  • Kyoto, Japan, 606-8507
    • Recruiting
    • Research Site
  • Kyoto, Japan, 602-8566
    • Recruiting
    • Research Site
  • Osaka, Japan, 541-8567
    • Recruiting
    • Research Site
  • Sakaishi, Japan, 591-8555
    • Recruiting
    • Research Site
  • Shinjuku-ku, Japan, 162-8655
    • Recruiting
    • Research Site
  • Wakayama, Japan, 641-8510
    • Recruiting
    • Research Site
  • Yokohama, Japan, 236-0051
    • Recruiting
    • Research Site
• Singapore
  • Singapore, Singapore, 168583
    • Recruiting
    • Research Site
  • Singapore, Singapore, 119082
    • Recruiting
    • Research Site
• South Korea
  • Cheongju-si, South Korea, 28644
    • Recruiting
    • Research Site
  • Namdong-gu, South Korea, 21565
    • Recruiting
    • Research Site
  • Seongnam-si, South Korea, 13496
    • Recruiting
    • Research Site
  • Seoul, South Korea, 03080
    • Recruiting
    • Research Site
  • Seoul, South Korea, 06351
    • Recruiting
    • Research Site
  • Seoul, South Korea, 5505
    • Recruiting
    • Research Site
  • Seoul, South Korea, 3722
    • Recruiting
    • Research Site
  • Suwon, South Korea, 16247
    • Recruiting
    • Research Site
  • Suwon, South Korea, 16499
    • Recruiting
    • Research Site
• Spain
  • A Coruña, Spain, 15006
    • Not yet recruiting
    • Research Site
  • Madrid, Spain, 28041
    • Not yet recruiting
    • Research Site
  • Manresa, Spain, 08243
    • Not yet recruiting
    • Research Site
  • Málaga, Spain, 29009
    • Not yet recruiting
    • Research Site
  • Santander, Spain, 39008
    • Not yet recruiting
    • Research Site
  • Valencia, Spain, 46010
    • Not yet recruiting
    • Research Site
• Taiwan
  • Liuying, Taiwan, 736
    • Recruiting
    • Research Site
  • Taichung, Taiwan, 40447
    • Recruiting
    • Research Site
  • Taichung, Taiwan, 402
    • Recruiting
    • Research Site
  • Tainan, Taiwan, 70403
    • Recruiting
    • Research Site
  • Tainan, Taiwan, 710
    • Recruiting
    • Research Site
  • Taipei, Taiwan, 100
    • Recruiting
    • Research Site
  • Taipei, Taiwan, 11217
    • Recruiting
    • Research Site
  • Taipei, Taiwan, 110
    • Recruiting
    • Research Site
  • Taoyuan, Taiwan, 00333
    • Recruiting
    • Research Site
• Thailand
  • Bangkok, Thailand, 10700
    • Not yet recruiting
    • Research Site
  • Bangkok, Thailand, 10330
    • Not yet recruiting
    • Research Site
  • Bangkok, Thailand, 10400
    • Not yet recruiting
    • Research Site
  • Banphaeo, Thailand, 74120
    • Not yet recruiting
    • Research Site
• United States
  • California
    • Santa Monica, California, United States, 90404
      • Not yet recruiting
      • Research Site
    • Santa Rosa, California, United States, 95403
      • Not yet recruiting
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Recruiting
      • Research Site
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Not yet recruiting
      • Research Site
  • Texas
    • Houston, Texas, United States, 77090
      • Not yet recruiting
      • Research Site
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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, unacceptable toxicity, withdrawal of consent, or other discontinuation criterion	Drug: Rilvegostomig; Rilvegostomig will be administered as IV infusion.; Other Names: AZD2936; Drug: Ramucirumab; Ramucirumab will be administered as IV infusion.; Other Names: 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, unacceptable toxicity, withdrawal of consent, or other discontinuation criterion	Drug: Rilvegostomig; Rilvegostomig will be administered as IV infusion.; Other Names: AZD2936; Drug: Ramucirumab; Ramucirumab will be administered as IV infusion.; Other Names: Cyramza
Experimental: Sub-study 3, investigate Dato-DXd + ramucirumab ± rilvegostomig in 2/3L AGA+ NSCLC; Participants will receive Dato-DXd + ramucirumab ± rilvegostomig until RECIST 1.1-defined radiological progression, unacceptable toxicity, withdrawal of consent, or other discontinuation criterion	Drug: Dato-DXd; Dato-DXd will be administered as IV infusion.; Other Names: DS-1062; Drug: Rilvegostomig; Rilvegostomig will be administered as IV infusion.; Other Names: AZD2936; Drug: Ramucirumab; Ramucirumab will be administered as IV infusion.; Other Names: Cyramza

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events (AE) and serious adverse events (SAE)	To assess the safety and tolerability	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	Through study completion, an average of 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best Overall Response(BOR)	BOR is the best response a participant has had following randomisation/start of dosing, but prior to starting any subsequent cancer therapy and up to and including RECIST progression or the last evaluable assessment in the absence of RECIST progression	Through study completion, an average of 3 years
Change in Target Lesion Tumor Size	The best percentage change from baseline in Target Lesion tumour size is the largest decrease (or smallest increase) from baseline for a participant, using RECIST 1.1 assessments	Through study completion, an average of 3 years
Disease Control Rate(DCR) at 12 Weeks	DCR at 12 weeks is defined as the percentage of participants who have a best objective response of confirmed CR or PR or who have SD for at least 11 weeks after start of treatment (to allow for an early assessment within the assessment window).	From Day 1 pre-dose to 12 weeks
Duration Of Response (DoR)	The DoR is defined as the time from the date of first documented objective response (which is subsequently confirmed) until date of first documented disease progression or death (by any cause in the absence of disease progression).	Through study completion, an average of 3 years
Overall Survival(OS)	OS is defined as the time from the start of treatment until death due to any cause.	Through study completion, an average of 3 years
Serum concentration	To assess the serum concentration of the novel anti-cancer agents in combination.	Through study completion, an average of 3 years
Maximum plasma drug concentration (Cmax)	To assess the Cmax of the novel anti-cancer agents in combination.	Through study completion, an average of 3 years
Immunogenicity of study interventions in participants receiving treatment	Presence of Anti Drug Antibodies（ADAs) for study interventions in serum/plasma	Through study completion, an average of 3 years
Progression free survival (PFS)	PFS is defined as the time from the start of treatment until the date of objective disease progression or death (by any cause in the absence of progression) per RECIST 1.1.	Through study completion, an average of 3 years

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Daiichi Sankyo

Study record dates

Study Major Dates

• Study Start (Actual): August 7, 2025
• Primary Completion (Estimated): April 6, 2029
• Study Completion (Estimated): April 6, 2029

Study Registration Dates

• First Submitted: July 4, 2025
• First Submitted That Met QC Criteria: July 25, 2025
• First Posted (Actual): August 1, 2025

Study Record Updates

• Last Update Posted (Actual): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 25, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Programmed death-ligand 1 (PD-L1); T-cell immunoreceptor with Ig and Immunoreceptor Tyrosine-based Inhibition Motif (ITIM) domains (TIGIT); Non-Small Cell Lung Cancer(NSCLC); Antibody-Drug Conjugates (ADCs)
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Ramucirumab
• Other Study ID Numbers: D6187C00001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No