New drug combinations for advanced non-small cell lung cancer

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

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.

Why it matters

Who can join: the full rules

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 it's running

• Research Site
  Santa Monica, California, United States Recruiting
• Research Site
  Atlanta, Georgia, United States Recruiting
• Research Site
  Fairfax, Virginia, United States Recruiting
• Research Site
  Changsha, China Recruiting
• Research Site
  Chengdu, China Recruiting
• Research Site
  Deyang, China Recruiting

+33 more sites. See ClinicalTrials.gov for the full list.

Study contacts

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

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.