PH2a, Platform Study of Novel Immunotherapy Combinations in Participants with Previously Untreated, Advanced/Metastatic NSCLC

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Glaxosmithkline Research & Development Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

2 Dec 2022 → ongoing

Decision date (initial)

2024-06-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-505057-40-00

EudraCT number

2021-005115-32

ClinicalTrials.gov

NCT05565378

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety

To monitor the safety of novel immunotherapy combinations

Conditions and MedDRA coding

Lung Cancer, Non-Small Cell

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Food And Drug Administration

EMA paediatric investigation plan (PIP)

EMEA-003452-PIP01-23

Plan to share IPD

Yes

IPD plan description

Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/ IPD Sharing Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months. IPD Sharing Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Is capable of giving signed informed consent as described in the protocol which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
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.
5. Provides a tumor tissue sample obtained at the time of or after the initial diagnosis of locally advanced or metastatic NSCLC. Although a fresh tumor tissue sample obtained during screening is preferred, an archival tumor specimen (collected within 2 years prior to screening*) is acceptable. Tumor tissue must be from a site not previously irradiated. Biopsies obtained prior to the administration of any systemic therapy administered for the treatment of a participant’s tumor (such as neoadjuvant/adjuvant therapy) are not acceptable. Needle or excisional biopsies or resected tissue is required. Cytological specimens such as fine needle aspirates, bone marrow samples, or cell blocks are not acceptable, nor are bone specimens.
6. Has a PD-L1-high (TC/TPS >/=50%) tumor.
7. Has measurable disease based on RECIST 1.1 as determined by the investigator.
8. Has an ECOG PS of 0 or 1.
9. Has adequate organ function as defined in the protocol
10. If of childbearing potential, female participants must be willing to use adequate contraception. A female participant is eligible to participate if she is not pregnant or breastfeeding, and 1 of the following conditions applies: Is a woman of non-childbearing potential (WONCBP) as defined in the protocol or Is a woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective as described in the protocol during the study intervention period and for at least 4 months after the last dose of study intervention. Female participant agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. A woman of childbearing potential (WOCBP) must not be pregnant; this will generally be confirmed via a negative highly sensitive serum pregnancy test within 7 days before the first dose of study intervention.

Exclusion criteria 27

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 (including, but not limited to, deletions in exon 19, exon 20 insertion mutation, and exon 21 [L858R] substitution mutation). All participants with nonsquamous histology must have been tested for EGFR mutation status using a tissue-based test; use of an approved test is strongly encouraged. Participants with squamous histology do not need to be tested for EGFR mutation status. Participants with nonsquamous histology and unknown or indeterminate EGFR status are excluded. b. ALK translocations that are sensitive to available targeted inhibitor therapy. All participants with nonsquamous histology must have been tested for ALK fusion mutation status using a tissue-based test; use of an approved test is strongly encouraged. Participants with squamous histology do not need to be tested for ALK mutation status. Participants with nonsquamous histology and with unknown or indeterminate ALK status are excluded. 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 the disease under study within the last 5 years, except as noted below: a. Participants may be enrolled in the study with a history of any other invasive malignancy for which the participant was definitively treated, from which the participant has been disease-free for at least 2 years, and which, in the opinion of the principal investigator and sponsor/medical monitor, is not expected to affect the evaluation of the effects of the study intervention on the currently targeted malignancy. b. Participants with curatively treated basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, in situ cervical cancer, and/or in situ breast cancer may be enrolled in the study.
6. Has known brain metastases meeting any of the following criteria: a. Symptomatic b. Untreated (NOTE: asymptomatic brain metastases are exclusionary if untreated) c. Actively progressing d. Any leptomeningeal disease (regardless of symptomatology, treatment status, or stability). NOTE: Participants with non-leptomeningeal brain metastases who have received prior therapy for brain metastases and have radiographically stable CNS disease for at least 4 weeks (confirmed by 2 brain scans taken at least 4 weeks apart, with at least 1 scan collected after treatment of brain metastases) may participate, provided they are neurologically stable for at least 2 weeks following treatment for brain metastases (i.e., any neurologic symptoms that developed either as a result of the brain metastases or their treatment must have returned to baseline or resolved) and prior to the first dose of study intervention. Corticosteroids must be discontinued at least 3 days prior to the first dose of study intervention.
7. Has autoimmune disease or syndrome (current or history thereof) that required systemic treatment within the past 2 years. Replacement therapies (e.g., insulin, thyroxine, or physiologic doses of corticosteroids for treatment of adrenal or pituitary insufficiency) are not considered systemic treatments and are allowed.
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. Note the following: a. Corticosteroid use is allowed as premedication for hypersensitivity reactions (e.g., IV contrast allergies/reactions). b. Use of topical, inhaled, or intranasal corticosteroids, local steroid injection, or steroid eye drops is allowed. c. Participants who receive daily steroid replacement therapy are an exception to this criterion. Daily prednisone at doses of ≤10 mg is an example of replacement therapy. Equivalent hydrocortisone doses are also permitted if administered as a replacement therapy.
9. Has received any live vaccine within 30 days prior to first dose of study intervention.
10. Has any history of idiopathic pulmonary fibrosis, organizing pneumonia, drug induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis.
11. Has symptomatic ascites, pleural effusion, or pericardial effusion. A participant who is clinically stable following treatment of these conditions (including therapeutic thoracentesis, paracentesis, or pericardiocentesis) is eligible if the participant otherwise meets entry criteria.
12. Has active inflammatory bowel disease, acute diverticulitis, intra-abdominal abscess, gastrointestinal obstruction, or peritoneal carcinomatosis.
13. Has a history or evidence of cardiac abnormalities, including: a. Recent history (i.e., within 6 months prior to the first dose of study intervention) of any of the following: i. Serious, uncontrolled cardiac arrhythmia or clinically significant ECG abnormalities including second-degree (Type II) or third-degree AV block (including complete heart block). ii. Myocardial infarction, acute coronary syndromes (including unstable angina pectoris), coronary angioplasty, stenting, bypass grafting, or newly diagnosed cardiomyopathy. iii. Symptomatic pericarditis. b. Congestive heart failure (Class III or IV) as defined by the New York Heart Association Functional Classification System [The Criteria Committee of the New York Heart Association, 1994]. c. Myocarditis of any grade.
14. Has QTcF >470 msec, or >480 msec for participants with bundle branch block.
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 cirrhosis.
16. Has had a severe infection requiring IV antibiotics or requiring hospitalization for infection or complication of infection or has had severe pneumonia within 4 weeks prior to the first dose of study intervention.
17. Has active tuberculosis.
18. Has a known HIV infection.
19. Has a history of severe hypersensitivity to mAbs or to any of the excipients in the formulations of the components of the study interventions
20. Has any serious and/or unstable pre-existing medical (aside from malignancy), psychiatric, or other condition that could, in the opinion of the investigator, interfere with participant’s safety, obtaining informed consent, or compliance with the study procedures
21. Is, at the time of signing the ICF, a regular user (including recreational use) of any illicit drugs or has a recent history (within the last year) of substance abuse (including alcohol) that, in the opinion of the investigator, would interfere with the evaluation of the study intervention or interpretation of safety.
22. Has a positive test for the presence of HBsAg at Screening or within 3 months prior to first dose of study intervention.
23. Has a positive hepatitis C antibody test result at Screening or within 3 months prior to first dose of study intervention. NOTE: Participants with a positive hepatitis C antibody test due to prior resolved disease can be enrolled only if a confirmatory negative hepatitis C RNA test is obtained.
24. Has a positive hepatitis C RNA test result at Screening or within 3 months prior to first dose of study intervention. NOTE: Participants with a negative hepatitis C antibody test are not required to also undergo hepatitis C RNA testing.
25. Has advanced, symptomatic, or visceral spread and is considered to be at imminent risk of life-threatening complications
26. Is currently participating in or has participated in a study of an investigational therapy within 4 weeks prior to the first dose of study intervention.
27. Has a history of allogeneic tissue/stem cell transplant or solid organ transplant

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Incidence of TEAEs and SAEs Incidence of TEAEs/SAEs leading to dose modifications (e.g., dose delay) or study intervention discontinuation

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Glaxosmithkline Research & Development Limited

Sponsor organisation

Glaxosmithkline Research & Development Limited

Address

G S K House, 980 Great West Road 980 Great West Road

City

Brentford

Postcode

TW8 9GS

Country

United Kingdom

Scientific contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trials Call Center

Public contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trials Call Center

Third parties 35

Locations

11 EU/EEA countries · 61 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 239 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications