Efficacy Comparison of Dostarlimab Plus Chemotherapy Versus Pembrolizumab Plus Chemotherapy in Participants With Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC)

Inclusion Criteria:

• Participant must be greater than equal to (>=) 18 years old, must be able tounderstand the study procedures, and agrees to participate in the study by providingwritten informed consent which includes compliance with the requirements andrestrictions listed in the informed consent form (ICF) and in this protocol.

• Participant has histologically- or cytologically-confirmed metastatic non-squamousNSCLC with documented absence of a sensitizing EGFR, ALK, ROS-1, or BRAFV600Emutation or other genomic aberration for which an approved targeted therapy isavailable. Mixed tumors will be categorized by the predominant cell type; if thetumor has predominantly squamous cell histology or if small cell elements arepresent, the participant is ineligible.

• Participants must have measurable disease, that is (i.e.) presenting with at least 1measurable lesion per RECIST v1.1 as determined by the local siteInvestigator/radiology assessment. Target lesions situated in a previouslyirradiated area are considered measurable if progression has been demonstrated insuch lesions and if there are other target lesions. If there is only 1 target lesionthat was previously irradiated, the participant is not eligible.

• Participant has documented PD L1 status by the 22C3 pharmDx assay (Agilent/Dako). Ifno prior PD L1 result is available at the time of Screening, the participant can betested locally using the stated method, or central PD L1 testing can be completed.Results are needed for stratification and must be available prior to randomization.

• Participant has an ECOG performance status score of 0 or 1.

• Participant has a life expectancy of at least 3 months.

• Participant has adequate organ function.

• Participant has recovered to Grade less than equal to (<=)1 from any prior treatmentrelated toxicities at the time of randomization. A participant with Grade 2 alopeciais an exception to this criterion and may qualify for this study.

• Contraceptive use by male and female participants should be consistent with localregulations regarding the methods of contraception for those participating inclinical studies.

• Male participants are eligible to participate if they agree to the following duringthe Treatment Period and for at least 150 days after the last dose of studytreatment:

• Refrain from donating sperm plus, either:

• Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent.

• Must agree to use contraception/barrier as follows:

• Agree to use a male condom (and should also be advised of the benefit for a femalepartner to use a highly effective method of contraception, as a condom may break orleak) when having sexual intercourse with a woman of childbearing potential (WOCBP)who is not currently pregnant.

• Agree to use a male condom when engaging in any activity that allows for passage ofejaculate to another person.

• A female participant is eligible to participate if she is not pregnant orbreastfeeding, and 1 of the following conditions applies:

• Is a woman of non childbearing potential (WONCBP),

• Is a WOCBP, using a contraceptive method that is highly effective (with a failurerate of <1% per year and, preferably, with low user dependency) during the TreatmentPeriod and for at least 180 days after the last dose of study treatment and agreesnot to donate eggs (ova or oocytes) for the purpose of reproduction during thisperiod. The Investigator should evaluate the potential for contraceptive methodfailure ( for example [e.g.], noncompliance and recently initiated) in relationshipto the first dose of study treatment.

• A WOCBP must have a negative highly sensitive pregnancy test (urine or serum, asrequired by local guidelines) within 72 hours before the first dose of studytreatment. If a urine test cannot be confirmed as negative (eg, an ambiguousresult), a serum pregnancy test is required. In such cases, the participant must beexcluded from participation if the serum pregnancy result is positive.

Exclusion Criteria:

• Participant has received prior systemic therapy for the treatment of metastaticNSCLC. Participants who have received neoadjuvant or adjuvant chemotherapy areeligible if the neoadjuvant/adjuvant therapy was completed at least 12 months priorto the development of metastatic disease.

• Participant has received prior therapy with a PD (L)1 or PD L2 inhibitor, acytotoxic T lymphocyte associated protein 4 (CTLA 4) inhibitor, a T cellimmunoglobulin and mucin domain containing 3 (TIM 3) inhibitor, or any otherimmunotherapy agent (eg, OX40) for the treatment of cancer.

• Participant has received radiation to the lung that is >30 Gray (Gy) within 6 monthsof the first dose of study treatment.

• Participant has completed palliative radiotherapy within 7 days of the first dose ofstudy treatment.

• Participant is ineligible if any of the following hepatic characteristics arepresent:

• Alanine aminotransferase (ALT) >2.5 times upper limit of normal (ULN) without livermetastases/tumor infiltration.

• ALT >5 times ULN with liver metastases/tumor infiltration.

• Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable ifbilirubin is fractionated and direct bilirubin is <35%)

• Current active liver or biliary disease (with the exception of Gilbert's syndrome orasymptomatic gallstones, liver metastases, or otherwise stable chronic liver diseaseper Investigator assessment)

• Participant has a corrected QT interval (QTc) >450 milliseconds (msec) (or QTc >480msec for participants with bundle branch block).

• Participant has had major surgery within 3 weeks of the first dose of studytreatment or has not adequately recovered from any AEs (Grade <=1) and/orcomplications from any major surgery. Surgical implantation of a port catheter isnot exclusionary.

• Participant has an additional malignancy or a history of prior malignancy, with theexception of adequately treated basal or squamous skin cancer, cervical carcinoma insitu, or bladder carcinoma in situ without evidence of disease, or had a malignancytreated with curative intent and with no evidence of disease recurrence for 5 yearssince the initiation of that therapy.

• Participant has known active brain metastases and/or leptomeningeal metastases.Participants who have received prior therapy for their brain metastases and haveradiographically stable central nervous system disease may participate, providedthey are neurologically stable for at least 2 weeks before study entry and must beoff corticosteroids within 3 days prior to the first dose of study treatment. Stablebrain metastases by this definition should be established prior to the first dose ofstudy treatment. Participants with known untreated, asymptomatic brain metastases (i.e., no neurological symptoms, no requirements for corticosteroids, no or minimalsurrounding edema, and no lesions >1.5 centimeters [cm]) may participate, but willrequire regular imaging of the brain as a site of disease.

• Participant has tested positive for the presence of hepatitis B surface antigen orhas a positive hepatitis C antibody test result at Screening, or within 3 monthsprior to first dose of study treatment. For potent immunosuppressive agents,participants who test positive for the presence of hepatitis B core antibody shouldalso be excluded.

• Participant has an active infection requiring systemic therapy within 1 week priorto the anticipated first dose of study treatment.

• Participant has known human immunodeficiency virus (HIV) (positive for HIV 1 or HIV 2 antibodies).

• Participant has active autoimmune disease that required systemic treatment in thepast 2 years, is immunocompromised in the opinion of the Investigator, or isreceiving systemic immunosuppressive treatment. Replacement therapy (e.g.,thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal orpituitary insufficiency) is not considered a form of systemic treatment.

• Participant has received systemic steroid therapy within 3 days prior to the firstdose of the study treatment or is receiving any other form of immunosuppressivemedication. Replacement therapy is not considered a form of systemic therapy. Use ofinhaled corticosteroids, local steroid injection, or steroid eye drops is allowed.

• Participant has symptomatic ascites or pleural effusion. A participant who isclinically stable following treatment of these conditions (including therapeuticthoraco or paracentesis) is eligible.

• Participant has current interstitial lung disease, current pneumonitis, or a historyof pneumonitis that required the use of oral or IV glucocorticoids to assist withmanagement. Lymphangitic spread of the NSCLC is not exclusionary.

• Participant has a history or current evidence of any medical condition, therapy, orlaboratory abnormality that might confound the study results, interfere with theirparticipation for the full duration of the study treatment, or indicate it is not inthe best interest of the participant to participate, in the opinion of theInvestigator.

• Participant has clinically active diverticulitis, intra-abdominal abscess,gastrointestinal obstruction, or peritoneal carcinomatosis.

• Participant has preexisting peripheral neuropathy that is Grade >=2 by NationalCancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0criteria.

• Participant has received a live vaccine within 30 days of the first dose of studytreatment. Seasonal flu vaccines that do not contain live virus are permitted.

• Participant does not meet requirements per local prescribing guidelines forreceiving treatment with either pemetrexed and cisplatin or carboplatin.

• Participant has sensitivity to any of the study treatments, or components thereof,or a history of drug or other allergy that, in the opinion of the Investigator orGlaxoSmithKline (GSK) Medical Monitor, contraindicates their participation.

• Participant is unable to interrupt aspirin or other nonsteroidal antiinflammatorydrugs (NSAIDs), other than an aspirin dose <=1.3 gram (g) per day, for a 5 dayperiod (8 day period for long acting agents, such as piroxicam).