Phase 2 Platform Study of Novel Immunotherapy Combinations in Participants with Previously Untreated Advanced/Metastatic NonSmallCell Lung Cancer

Phase 1

• Conditions: on-small Cell Lung Cancer; MedDRA version: 21.1Level: PTClassification code 10059515Term: Non-small cell lung cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2021-005115-32-BE
• Lead Sponsor: GlaxoSmithKline Research & Development Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-08-05
• Last Update Posted: 18 June 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

Key Inclusion Criteria
1. Is capable of giving signed informed consent
2. Is, at the time of signing the ICF, at least 18 years old or the legal age of consent in the jurisdiction in which the study is taking place.
3. Has a histologically or cytologically confirmed diagnosis of locally advanced unresectable NSCLC not eligible for curative surgery and/or definitive radiotherapy with or without chemotherapy or metastatic NSCLC (squamous or nonsquamous). Mixed tumors will be categorized by the predominant cell type; if small cell or neuroendocrine elements are present, the participant is ineligible.
4. Has not received prior systemic therapy for their locally advanced or metastatic NSCLC.
NOTE: Completion of treatment with cytotoxic chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy is allowed if therapy was completed at least 6 months prior to the diagnosis of locally advanced or metastatic disease. Prior treatment with neoadjuvant/adjuvant immunotherapy is not permitted.
5. Has a PD-L1-high tumor performed locally or confirmed via central testing.
6. Has measurable disease based on RECIST 1.1 (Appendix 7), as determined by the investigator.
7. Has an ECOG PS 0 or 1.
8. Has adequate organ function
9. If of childbearing potential, female participants must be willing to use adequate contraception.

Refer to the protocol for full list of inclusion criteria

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 165
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 135

Exclusion Criteria

Key Exclusion criteria
1. Has NSCLC with a tumor that harbors any of the following molecular alterations:
a. EGFR mutations that are sensitive to available targeted inhibitor therapy
b. ALK translocations that are sensitive to available targeted inhibitor therapy.
c. Any other known genomic aberrations or oncogenic driver mutations for which a locally approved targeted therapy is available for first line treatment of locally advanced or metastatic NSCLC.
2. Has had major surgery within 4 weeks of the first dose of study intervention or has received lung radiation therapy of >30 Gy (for any purpose, including palliatively) within 6 months prior to the first dose of study intervention.
3. Has received prior therapy with any immune checkpoint inhibitors, including antibodies or drugs targeting PD-1, PD-L1, CTLA-4, TIGIT, CD96, or other checkpoint pathways.
4. Has never smoked, defined as smoking <100 tobacco cigarettes in a lifetime.
5. Has an invasive malignancy or history of invasive malignancy other than disease under study within the last 5 years (clinical exceptions apply as per protocol).
6. Has known symptomatic, untreated, or actively progressing brain metastases and/or leptomeningeal disease. Participants who have received prior therapy for brain metastases and have stable CNS disease may participate, provided they are neurologically stable for at least 2 weeks before randomization and have been off corticosteroids for at least 3 days prior to the date of randomization.
7. Has autoimmune disease or syndrome (current or history thereof) that required systemic treatment within the past 2 years.
8. Has received systemic steroid therapy =3 days prior to the first dose of study intervention or is receiving any other form of immunosuppressive medication. Replacement therapy is not considered
a form of systemic therapy.
9. Has received any live vaccine within 30 days prior to first dose of study intervention. NOTE: mRNA and adenoviral-based COVID-19 vaccines are considered non-live. Study participants can be vaccinated against COVID-19 using vaccines authorized via the appropriate regulatory mechanisms (e.g., Emergency Use Authorization, Conditional Marketing Authorization, or Marketing Authorization Application). Refer to Section 6.8, Section 11.7.3, and the SRM for further information regarding COVID-19 vaccination recommendations and data to be collected in the eCRF. .
10. Has any history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis.
11. Has symptomatic ascites or pleural effusion. A participant who is clinically stable following treatment of these conditions (including therapeutic thoracentesis or paracentesis) is eligible if the participant otherwise meets entry criteria.
12. Has active inflammatory bowel disease, acute diverticulitis, intraabdominal abscess, gastrointestinal obstruction, or peritoneal carcinomatosis.
13. Has a history or evidence of cardiac abnormalities within the 6 months prior to enrollment.
14. QTcF >470 msec, or >480 msec for participants with bundle branch block. QTcF is QT corrected for heart rate according to Fridericia's formula and can be machine calculated or manually over-read.
15. Has current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosi

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified