Novel Combinations for Lung Cancer

(LIBRA Trial)

Recruiting at 46 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AstraZeneca

Must not be taking: Chemotherapy, Immunotherapy, Anticoagulants, others

Disqualifiers: Autoimmune disorders, Brain metastases, Infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 3 years

278 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatment combinations for individuals with advanced lung cancer that has spread or cannot be removed. It tests several drugs, including Dato-DXd (an experimental treatment), Ramucirumab (a monoclonal antibody), and Rilvegostomig (an experimental treatment), to assess their safety and effectiveness against the cancer. Individuals diagnosed with advanced non-small cell lung cancer (NSCLC) who have specific protein markers in their cancer cells might be suitable candidates. The goal is to find treatments that can better manage the disease. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that you do not take any other anti-cancer treatments while participating. If you are on such treatments, you will need to stop them before joining the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that earlier studies have assessed the safety of the treatments in this study. For the combination of rilvegostomig and ramucirumab, studies have examined its tolerability. These studies focus on its safety for treating non-small cell lung cancer (NSCLC), a type of lung cancer. So far, this combination is generally well-tolerated, with common side effects like tiredness and nausea.

For the Dato-DXd and ramucirumab treatment, research indicates that Dato-DXd has been tested in patients who have already tried other treatments for NSCLC. It appears to help patients live longer without disease progression. Some frequent side effects include nausea and low blood cell counts, but these are usually manageable.

When examining the combination of Dato-DXd, ramucirumab, and rilvegostomig, earlier research found that the side effects are similar to those known for each drug alone. This suggests the combination does not introduce new risks beyond what is already known for each drug.

Overall, past studies suggest that the treatments in this trial are generally well-tolerated, but like any treatment, they can have side effects. Participants should consult their healthcare provider to fully understand what to expect. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer novel approaches for treating non-small cell lung cancer (NSCLC). Unlike standard treatments, which often focus on chemotherapy or single-agent targeted therapies, these investigational treatments explore combinations like Dato-DXd, ramucirumab, and rilvegostomig. Dato-DXd is unique because it combines an antibody-drug conjugate with precision targeting to deliver chemotherapy directly to cancer cells. Ramucirumab works by inhibiting angiogenesis, cutting off the blood supply that tumors need to grow. Rilvegostomig represents a new approach by modulating immune responses, potentially enhancing the body's ability to fight the cancer. These combinations could provide more effective and targeted options for patients, especially those with specific biomarkers like PD-L1 expressions.

What evidence suggests that this trial's treatments could be effective for lung cancer?

Research has shown that combining rilvegostomig and ramucirumab could effectively treat non-small cell lung cancer (NSCLC). In this trial, one group of participants will receive rilvegostomig with or without ramucirumab, while another group will specifically investigate rilvegostomig combined with ramucirumab for patients with PD-L1 levels of 1-49%. Rilvegostomig has demonstrated positive results in patients who haven't received certain previous treatments, with lasting effects regardless of PD-L1 levels, a protein that helps cancer evade the immune system.

Another group in this trial will explore the combination of Dato-DXd and ramucirumab, with or without rilvegostomig, for NSCLC, particularly for non-squamous types, which has shown early signs of success. Ramucirumab, when combined with other drugs like docetaxel, has proven effective as a second-line treatment for advanced lung cancer. These combinations hold potential in fighting advanced NSCLC. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

Adults over 18 with advanced or metastatic non-small cell lung cancer (NSCLC) can join this trial. They should be relatively healthy, able to perform daily activities with ease or minor difficulty, and have a life expectancy of at least 12 weeks. Participants need a specific type of tumor that can be measured and must provide tissue samples. Those with certain genetic mutations in their cancer are excluded.

Inclusion Criteria

I am 18 years old or older.

My doctor expects me to live for at least 12 more weeks.

I can provide a sample of my tumor tissue.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive novel combination treatments until RECIST 1.1-defined radiological progression, unacceptable toxicity, or other discontinuation criteria

Up to 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Dato-DXd
• Ramucirumab
• Rilvegostomig

Trial Overview The study is testing new combinations of drugs: Ramucirumab, Dato-DXd, and Rilvegostomig for NSCLC treatment. It's an open-label Phase II trial conducted globally across multiple centers to assess safety, tolerability, and how well the drug combos work against tumors.

How Is the Trial Designed?

Group I: Sub-study 3, investigate Dato-DXd + ramucirumab ± rilvegostomig in 2L AGA+ NSCLC Experimental Treatment 3 Interventions

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

Group II: Sub-study 2, investigate rilvegostomig + ramucirumab in 1L non-AGA NSCLC with PD-L1 1-49% Experimental Treatment 2 Interventions

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

Group III: Sub-study 1, investigate rilvegostomig± ramucirumab in 1L non-AGA NSCLC with PD-L1 ≥50% Experimental Treatment 2 Interventions

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

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Daiichi Sankyo

Industry Sponsor

Trials

443

Recruited

493,000+

Hiroyuki Okuzawa

Daiichi Sankyo

Chief Executive Officer

Degree in Social Sciences from Hitotsubashi University

Yuki Abe

Daiichi Sankyo

Chief Medical Officer since 2023

MD

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07098338

NCT07098338 | A Study of Novel Combinations in Non- ... A Study of Novel Combinations in Non-Small Cell Lung Cancer (NSCLC) (LIBRA) ... Sub-study 3, investigate Dato-DXd + ramucirumab ± rilvegostomig in 2L AGA+ NSCLC.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37731641/

Clinical outcomes of ramucirumab plus docetaxel in the ... These results support the combination of ramucirumab plus docetaxel as an effective and safe subsequent therapy for the treatment of patients with metastatic ...

3. tandfonline.com tandfonline.com/doi/full/10.1080/14712598.2025.2519532?src=

An evaluation of datopotamab deruxtecan for the treatment ... Dato-DXd is a promising new option for NSCLC treatment with clear evidence of activity, shown early signals of efficacy, particularly in non-squamous NSCLC and ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO-24-02786

Therapy for Stage IV Non–Small Cell Lung Cancer Without ... The confirmed objective response rates (ORRs) were 26.5% for cohort 1 and 34.1% for cohort 1A, with median durations of response of 5.8 months ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38241181/

Prospective Observational Study of Ramucirumab Plus ... Our results showed that RAM plus DOC after combined chemoimmunotherapy might be an effective and relatively feasible second-line treatment for patients with ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e20674

A meta-analysis analyzing the efficacy and safety of ... Recent trials have demonstrated promising efficacy for Dato-DXd in pre-treated advanced NSCLC compared to 2nd line chemotherapy.

7. jto.org jto.org/article/S1556-0864(25)00761-0/fulltext

A Pooled Analysis of Datopotamab Deruxtecan in Patients ... Median progression-free survival and overall survival were 5.8 (95% CI: 5.4–8.2) and 15.6 months (95% CI: 13.1–19.0), respectively. The safety profile of Dato- ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12448455/

Datopotamab deruxtecan–associated select adverse events Dato-DXd demonstrated statistically significant improvement in median progression-free survival (mPFS) over docetaxel in patients with previously treated ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S1556086425007610

A Pooled Analysis of Datopotamab Deruxtecan in Patients ... Here we report exploratory pooled efficacy and safety analyses of Dato-DXd in patients with pretreated advanced or metastatic NSCLC harboring ...