KEYMAKER-U01 Umbrella Master Study: Studies of Investigational Agents With Either Pembrolizumab (MK-3475) Alone or With Pembrolizumab PLUS Chemotherapy in Participants With Non-small Cell Lung Cancer (NSCLC) (MK-3475-U01/KEYMAKER-U01)

Inclusion Criteria:

• Has histologically- or cytologically-confirmed diagnosis of Stage IV squamous ornonsquamous NSCLC

• Participants with nonsquamous NSCLC who are not eligible for an approved targetedtherapy

• Is able to to provide archival tumor tissue sample collected either within 5 yearsor within the interval from completion of last treatment but before entering thescreening period or newly obtained core or excisional biopsy of a tumor lesion notpreviously irradiated obtained within 90 days of treatment initiation

• Has not received prior systemic treatment for their metastatic NSCLC

• Has adequate organ function within 10 days of initiation of study treatment

• Male participants must agree to use contraception and should refrain from donatingsperm during the treatment period and:

• Substudy 01A: for at least 120 days after the last dose of pembrolizumab and for atleast 180 days after the last dose of chemotherapy

• Substudies 01B and 01C: for at least 120 days after study treatments

• Substudy 01E: for at least 100 days after the last dose of MK-2870 or MK-7684A, andfor at least 90 days after the last dose of radiation therapy

• Substudy 01G: for at least 90 days after the last dose of chemotherapy or 120 daysafter the last dose of HER3-DXd

• Substudies 01H and 01I: for at least 120 days after the last dose of I-DXd or R-DXdand 95 days after the last dose of docetaxel

• Female participants must not be pregnant or breastfeeding, and at least 1 of thefollowing conditions apply:

1. Not a woman of childbearing potential (WOCBP), OR

2. A WOCBP who agrees to use contraception during the treatment period and:

• Substudy 01A: for at least 120 days after the last dose of pembrolizumab and for atleast 180 days after the last dose of chemotherapy.

• Substudies 01B and 01C: for at least 120 days after study treatment

• Substudy 01E: for at least 120 days after the last dose of pembrolizumab, 190 daysafter the last dose of MK-2870, 120 days after the last dose of MK-7684A, 120 daysafter the last dose of vibostolimab, 190 days after the last dose of chemotherapy,and 180 days after the last dose of radiation therapy

• Substudy 01G: for at least 120 days after the last dose of pembrolizumab, 180 daysafter the last dose of chemotherapy, and 210 days after the last dose of HER3-DXd

• Substudies 01H and 01I: for at least 210 days after the last dose of I-DXd or R-DXdand 35 days after the last dose of docetaxel

• Substudies 01A, 01B, and 01C only:

• Is able to complete all screening procedures within the 35-day screening window

• Substudies 01A and 01B only:

• Has not received prior systemic treatment for their metastatic NSCLC

• Substudy 01B only:

• Has a programmed death-ligand 1 (PD-L1) Tumor Proportion Score (TPS) ≥1%

• Substudy 01C only:

• Has progressed on treatment with an anti-PD-(L)1 monoclonal antibody (mAb)administered either as monotherapy, or in combination with other checkpointinhibitors or other therapies

• Has progressive disease during/after platinum doublet chemotherapy

• Substudy 01E only:

• Participant has previously untreated and pathologically confirmed resectable StageII, IIIA, or IIIB (N2) NSCLC per American Joint Committee on Cancer 8th Edition

• Tumors must be resectable in the judgment of a thoracic surgeon

Exclusion Criteria:

• Has preexisting neuropathy that is moderate in intensity

• Has received a live or live-attenuated vaccine within 30 days before the first doseof study treatment. Any licensed COVID-19 vaccine (including for Emergency Use) in aparticular country is allowed as long as they are messenger ribonucleic acid (mRNA)vaccines, adenoviral vaccines, or inactivated vaccines. Investigational vaccines (ie, those not licensed or approved for Emergency Use) are not allowed

• Is currently participating in or has participated in a study of an investigationalagent or has used an investigational device within 4 weeks before the first dose ofstudy treatment

• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form ofimmunosuppressive therapy within 7 days before the first dose of study treatment

• Has an active autoimmune disease that has required systemic treatment in the past 2years

• Has a history of (noninfectious) pneumonitis/interstitial lung disease that requiredsteroids or has current pneumonitis/interstitial lung disease

• Has an active infection requiring systemic therapy

• Has a known history of HIV infection

• Has a known history of Hepatitis B or known active Hepatitis C virus infection

• Has had an allogenic tissue/solid organ transplant

• Substudies 01A, 01B, and 01C only:

• Has a diagnosis of small cell lung cancer

• Has a known additional malignancy that is progressing or has required activetreatment within the past 2 years

• Has known active central nervous system (CNS) metastases and/or carcinomatousmeningitis

• Has clinically significant cardiac disease, including unstable angina, acutemyocardial infarction within 6 months from Day 1 of study treatment administration,or New York Heart Association Class III or IV congestive heart failure

• Has had major surgery <3 weeks before the first dose of study treatment

• Is expected to require any other form of antineoplastic therapy while on study

• Has received prior radiation therapy to the lung that is >30 Gray (Gy) within 6months of the first dose of study treatment

• Has received any prior immunotherapy and was discontinued from that treatment due toa severe or worse immune-related adverse event (irAE)

• Has had chemotherapy or biological cancer therapy within 4 weeks before the firstdose of study treatment or has not recovered to Common Terminology Criteria forAdverse Events (CTCAE) Grade 1 or better from the AEs due to cancer therapeuticsadministered more than 4 weeks before the first dose of study treatment (includingparticipants who had previous immunomodulatory therapy with residual irAEs)

• Previously had a severe hypersensitivity reaction to treatment with monoclonalantibodies (including pembrolizumab) and/or any of their excipients

• Is pregnant or breastfeeding or expecting to conceive or father children within theprojected duration of the study, starting with the screening visit through 120 daysafter the last dose of study treatment

• Substudy 01A only:

• Has symptomatic ascites or pleural effusion (if receiving pemetrexed)

• Has a history or current evidence of a gastrointestinal (GI) condition (e.g.inflammatory bowel disease, Crohn's disease, ulcerative colitis) or impaired liverfunction or diseases that in the opinion of the investigator may significantly alterthe absorption or metabolism of oral medications

• Is getting chemotherapy and has clinically active diverticulitis, intra-abdominalabscess, GI obstruction, or peritoneal carcinomatosis

• Is unable to interrupt aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs), other than aspirin dose less than or equal to 1.3 gm/day for a 5-dayperiod (8-day period for long acting agents such as peroxicam), for participants whowill receive pemetrexed

• Is unable or unwilling to take folic acid or vitamin B12 supplementation, forparticipants who will receive pemetrexed

• Has a known sensitivity to any component of carboplatin, paclitaxel, pemetrexed orany of their excipients

• Substudies 01A and 01B only:

• Has received prior systemic cytotoxic chemotherapy or other targeted or biologicalantineoplastic therapy for metastatic disease

• Has received prior therapy with an anti-programmed cell death-1 (PD-1),anti-programmed cell death-ligand 1 (PD-L1), or anti-PD-L2 agent or prior therapytargeting other immunoregulatory receptors or mechanisms

• Substudy 01C only:

• Has received prior therapy targeting other immuno-regulatory receptors ormechanisms, not including anti-PD-(L)1 agents

• Has participated in Substudies 01A or 01B

• Substudy 01E only:

• Has one of the following tumor locations/types:

• NSCLC involving the superior sulcus

• Large-cell neuro-endocrine cancer

• Mixed tumors containing small cell and non-small cell elements

• Sarcomatoid tumor

• Documentation by local test report indicating presence of ALK generearrangements (ALK status not required and unknown or undetermined ALK statusare acceptable)

• Has a known severe hypersensitivity (≥ Grade 3) to any of the investigational agentsand/or any of their excipients, the study chemotherapy agents and/or to any of theirexcipients, pembrolizumab and/or any of its excipients, and/or to another biologictherapy

• History of documented severe dry eye syndrome, severe Meibomian gland disease and/orblepharitis, or corneal disease that prevents/delays corneal healing.

• Has active inflammatory bowel disease requiring immunosuppressive medication orprevious history of inflammatory bowel disease

• Has uncontrolled, significant cardiovascular disease or cerebrovascular disease

• Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or withan agent directed to another stimulatory or coinhibitory T-cell receptor

• Received prior radiotherapy within 2 weeks of start of study intervention, orradiation related toxicities, requiring corticosteroids

• Has a known additional malignancy that is progressing or has required activetreatment within the past 5 years

• Has not adequately recovered from major surgery or has ongoing surgicalcomplications

• Substudy 01G only:

• Has a known severe hypersensitivity (≥ Grade 3) to any of the investigational agentsand/or any of their excipients

• Has active inflammatory bowel disease requiring immunosuppressive medication orprevious history of inflammatory bowel disease

• Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or withan agent directed to another stimulatory or coinhibitory T-cell receptor

• Has a known additional malignancy that is progressing or has required activetreatment within the past 3 years