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

Inclusion Criteria:

• Participants capable of giving signed informed consent/assent.

• Male or female, aged 18 years or older at the time consent is obtained. Participantsin 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 amaximum of 2 lines of systemic treatment for locally/regionally advanced recurrent,Stage IIIb/Stage IIIc/Stage IV or metastatic disease. Two components of treatmentmust have been received in the same line or as separate lines of therapy: i) No morethan or less than 1 line of platinum-containing chemotherapy regimen, and ii) Nomore than or less than 1 line of Programmed cell death ligand 1 (PD[L]1) monoclonalantibody (mAb) containing regimen. b) Participants with known BRAF molecular alterations must have had diseaseprogression after receiving the locally available SoC treatment for the molecularalteration. c) Participants who received prior anti-PD(L)1 therapy must fulfill the followingrequirements: i) Have achieved a CR, PR or SD and subsequently had diseaseprogression (per RECIST 1.1 criteria) either on or after completing PD(L)1 therapyii) Have not progressed or recurred within the first 12 weeks of PD(L)1 therapy,either clinically or per RECIST 1.1 criteria

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

• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 or 1.

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

• Adequate organ function as defined in the protocol.

• A male participant must agree to use a highly effective contraception during thetreatment period and for at least 120 days after the last dose of study treatmentand refrain from donating sperm during this period.

• A female participant is eligible to participate if she is not pregnant, notbreastfeeding, and at least 1 of the following conditions apply: i) Not a woman of childbearing potential (WOCBP) or ii) A WOCBP who agrees to followthe contraceptive guidance during the treatment period and for at least 120 daysafter the last dose of study treatment.

• Life expectancy of at least 12 weeks.

Exclusion Criteria:

• Participants who received prior treatment with the following therapies (calculationis based on date of last therapy to date of first dose of study treatment):

1. Docetaxel at any time.

2. Any of the investigational agents being tested in the current study.

3. Systemic approved or investigational anticancer therapy within 30 days or 5half-lives of the drug, whichever is shorter. At least 14 days must haveelapsed between the last dose of prior anticancer agent and the first dose ofstudy drug is administered.

4. Prior radiation therapy: permissible if at least one non-irradiated measurablelesion is available for assessment per RECIST version 1.1 or if a solitarymeasurable lesion was irradiated, objective progression is documented. A washout of at least 2 weeks before start of study drug for radiation of anyintended use is required.

• Received greater than (>)2 prior lines of therapy for NSCLC, including participantswith BRAF molecular alternations.

• Invasive malignancy or history of invasive malignancy other than disease under studywithin the last 2 years, except

• Any other invasive malignancy for which the participant was definitivelytreated, has been disease-free for at least 2 years and in the opinion of theprincipal investigator and GlaxoSmithKline Medical Monitor will not affect theevaluation of the effects of the study treatment on the currently targetedmalignancy, may be included in this clinical trial.

• Curatively treated non-melanoma skin cancer or successfully treated in situcarcinoma.

• Carcinomatous meningitis (regardless of clinical status) and uncontrolled orsymptomatic Central nervous system (CNS) metastases.

• Major surgery less than or equal to (<=) 28 days of first dose of study treatment.

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

• Receiving systemic steroids (>10 milligrams [mg]) oral prednisone or equivalent) orother 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:

1. Greater than or equal to (>=) Grade 3 toxicity considered related to priorimmunotherapy and that led to treatment discontinuation.

2. History of myocarditis of any grade during a previous treatment withimmunotherapy

3. Toxicity related to prior treatment that has not resolved to <= Grade 1 (exceptalopecia, hearing loss, endocrinopathy managed with replacement therapy, andperipheral 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), interstitiallung 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 thatrequired surgery, acute diverticulitis, inflammatory bowel disease, orintra-abdominal abscess.

• History or evidence of cardiac abnormalities within the 6 months prior to enrollmentwhich include

1. Serious, uncontrolled cardiac arrhythmia or clinically significantelectrocardiogram abnormalities including second degree (Type II) or thirddegree atrioventricular block.

2. Cardiomyopathy, myocardial infarction, acute coronary syndromes (includingunstable angina pectoris), coronary angioplasty, stenting or bypass grafting.

3. Symptomatic pericarditis.

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

• Active infection requiring systemic therapy <=7 days prior to first dose of studytreatment.

• Participants with known human immunodeficiency virus infection.

• Participants with history of severe hypersensitivity to mAb or hypersensitivity toany of the study treatment(s) or their excipients.

• Participants requiring ongoing therapy with a medication that is a strong inhibitoror 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'ssafety, obtaining informed consent, or compliance to the study procedures in theopinion of the investigator.

• Pregnant or lactating female participants.

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

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

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

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

• Receipt of transfusion of blood products (including platelets or red blood cells) oradministration of colony-stimulating factors (including granulocyte colonystimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor, andrecombinant erythropoietin) within 14 days before the first dose of studyintervention.