A Study of Novel Combinations in Non-Small Cell Lung Cancer (NSCLC)
18 Years and older, Male and Female
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.
Objectives
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).
Eligibility
- 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.
Treatment Sites in Georgia
**Clinical trials are research studies that involve people. These studies test new ways to prevent, detect, diagnose, or treat diseases. People who take part in cancer clinical trials have an opportunity to contribute to scientists’ knowledge about cancer and to help in the development of improved cancer treatments. They also receive state-of-the-art care from cancer experts...
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