Platform Trial of Novel Regimens Versus Standard of Care (SoC) in Non-small Cell Lung Cancer (NSCLC)

• Status: Recruiting
• Trial end date: 2025-03-05
• Target enrollment: 0
• Participant gender: All

Summary

This study will compare the clinical activity of novel regimens (in combination or as single agents) to standard of care in participants with relapsed/refractory advanced NSCLC. The study will be conducted in two parts; Part 1 is an optional, non-randomized part based on safety and pharmacokinetics/pharmacodynamics (PK/PD) evaluation intended to generate additional data to qualify novel regimens for the randomized study. Part 2 is a randomized, Phase II study comparing the efficacy and safety of these novel regimens with SoC.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: GlaxoSmithKline
• Treatments: Docetaxel; Ipilimumab; Niraparib

Criteria

Inclusion Criteria:

• Participants capable of giving signed informed consent/assent.

• Male or female, aged 18 years or older at the time consent is obtained. Participants in Korea must be age 19 years or older at the time consent is obtained.

• Participants with histologically or cytologically confirmed diagnosis of NSCLC (squamous or non-squamous) and: a. Documented disease progression based on radiographic imaging, during or after a maximum of 2 lines of systemic treatment for locally/regionally advanced recurrent, Stage IIIb/Stage IV or metastatic disease. Two components of treatment must have been received in the same line or as separate lines of therapy: i. No more than or less than 1 line of platinum-containing chemotherapy regimen, and ii. No more than or less than 1 line of Programmed cell death ligand 1 (PD[L]1) monoclonal antibody (mAb) containing regimen. b. Participants with known BRAF molecular alterations must have had disease progression after receiving the locally available SoC treatment for the molecular alteration.

• Measurable disease, presenting with at least 1 measurable lesion per RECIST 1.1.

• ECOG PS score of 0 or 1.

• A tumor tissue sample obtained at any time from the initial diagnosis of NSCLC to time of study entry is mandatory. Although a fresh tumor tissue sample obtained during screening is preferred, archival tumor specimen is acceptable.

• Adequate organ function.

Exclusion Criteria:

• Participants who received prior treatment with the following therapies (calculation is based on date of last therapy to date of first dose of study treatment): a. Docetaxel at any time. b. Any of the investigational agents being tested in the current study, including an experimental ICOS agonist. c. Systemic approved or investigational anticancer therapy within 30 days or 5 half-lives of the drug, whichever is shorter. At least 14 days must have elapsed between the last dose of prior anticancer agent and the first dose of study drug is administered. d. Prior radiation therapy: permissible if at least one non-irradiated measurable lesion is available for assessment per RECIST version 1.1 or if a solitary measurable lesion was irradiated, objective progression is documented. A wash out of at least 2 weeks before start of study drug for radiation of any intended use is required.

• Received >2 prior lines of therapy for NSCLC, including participants with BRAF molecular alternations.

• Invasive malignancy or history of invasive malignancy other than disease under study within the last 2 years, except a: Any other invasive malignancy for which the participant was definitively treated, has been disease-free for at least 2 years and in the opinion of the principal investigator and GSK Medical Monitor will not affect the evaluation of the effects of the study treatment on the currently targeted malignancy, may be included in this clinical trial. b: Curatively treated non-melanoma skin cancer or successfully treated in situ carcinoma.

• Central nervous system (CNS) metastases, with the following exception: Participants with asymptomatic CNS metastases who are clinically stable and have no requirement for steroids for at least 14 days prior to first dose of study treatment.

• Major surgery <= 28 days of first dose of study treatment.

• Autoimmune disease (current or history) or syndrome that required systemic treatment within the past 2 years. Replacement therapies which include physiological doses of corticosteroids for treatment of endocrinopathies (for example, adrenal insufficiency) are not considered systemic treatments.

• Receiving systemic steroids (oral prednisone or equivalent) or other immunosuppressive agents within 7 days prior to first dose of study treatment.

• Prior allogeneic/autologous bone marrow or solid organ transplantation.

• Receipt of any live vaccine within 30 days prior to first dose of study treatment.

• Toxicity from previous anticancer treatment that includes: a. >= Grade 3 toxicity considered related to prior immunotherapy and that led to treatment discontinuation. b. Toxicity related to prior treatment that has not resolved to <= Grade 1 (except alopecia, hearing loss, endocrinopathy managed with replacement therapy, and peripheral neuropathy which must be <= Grade 2).

• History (current and past) of idiopathic pulmonary fibrosis, pneumonitis (for past- pneumonitis exclusion only if steroids were required for treatment), interstitial lung disease, or organizing pneumonia.

• Recent history (within the past 6 months) of uncontrolled symptomatic ascites, pleural or pericardial effusions.

• Recent history (within the past 6 months) of gastrointestinal obstruction that required surgery, acute diverticulitis, inflammatory bowel disease, or intra-abdominal abscess.

• History or evidence of cardiac abnormalities within the 6 months prior to enrollment.

• Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypo-albuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis.

• Active infection requiring systemic therapy.

• Participants with known human immunodeficiency virus infection.

• Participants with history of severe hypersensitivity to mAb or hypersensitivity to ingredients used in the formulation of docetaxel.

• Participants requiring ongoing therapy with a medication that is a strong inhibitor or inducer of the cytochrome P 3A4 (CYP3A4) enzymes.

• Any serious and/or unstable pre-existing medical (aside from malignancy), psychiatric disorder, or other condition that could interfere with participant's safety, obtaining informed consent, or compliance to the study procedures in the opinion of the investigator.

• Pregnant or lactating female participants.

• Participant who is currently participating in or has participated in a study of an investigational device within 4 weeks prior to the first dose of study treatment.

• Participants with presence of hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to first dose of study intervention.

• Participants with positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study intervention.

• Participants with positive hepatitis C ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study treatment.