Study of TSR-042, an Anti-programmed Cell Death-1 Receptor (PD-1) Monoclonal Antibody, in Participants With Advanced Solid Tumors

Inclusion Criteria:

• Participant is at least 18 years of age.

• Participant has proven recurrent or advanced solid tumor and has disease progressionafter treatment with available anticancer therapies, or is intolerant to treatmentthat meets the following requirements for the part of the study they willparticipate in:

A. Part 1: Any histologically or cytologically proven recurrent or advanced solid tumor B. Part 2A: : Any histologically or cytologically proven recurrent or advanced solid tumor

C. Part 2B: Histologically of cytologically proven recurrent or advanced solid tumor with measurable lesion(s) per RECIST version 1.1 and meets one of the following disease types:

The criteria below should be met for participant participating in: 1) Cohort A1 (dMMR/MSI-H endometrial cancer) and 2) Cohort A2 (MMR-proficient/MSS endometrial cancer)

• Participants who have progressed on or after platinum doublet therapy

• Participants have received no more than 2 lines of anticancer therapy for recurrentor advanced (>=Stage IIIB) disease. Prior treatment with hormone therapies isacceptable and does not count towards the number of anticancer therapies noted inthe criterion above for this cohort.

• All endometrial cancer histologies are allowed except endometrial sarcoma (includingcarcinosarcoma).

• Participants must submit 2 scans demonstrating increase in tumor measurement thatmeet criteria for PD on or after the latest systemic anticancer therapy based onRECIST Version 1.1 to Central Radiology prior to the first dose of dostarlimab.

• Presence of at least 1 measurable lesion on Baseline scan will be confirmed bycentral radiology review.

• Status of tumor MMR/MSI: Participants can be screened based on local MMR/MSI testingresults using immunohistochemistry (IHC), polymerase chain reaction (PCR), or nextgeneration sequencing (NGS) performed in a certified local laboratory, butparticipant eligibility needs to be determined by MMR IHC results. For participantwith available local MMR IHC results for the respective cohort(s), tumor sampleshave to be submitted to a central IHC laboratory and its quality has to be checkedand cleared prior to Cycle 1 Day 1 (C1D1). For participants without available localMMR IHC test results (participants with local PCR or NGS test results), central IHCresults have to confirm eligibility prior to proceeding with other screeningprocedures. After the central IHC test is completed, remaining tumor tissue may betested for further exploratory biomarkers or may be sent to a central NGS laboratoryfor further testing.

3. Cohort E - Participants with NSCLC who progressed after at least 1 priorplatinum-based systemic chemotherapy regimen for recurrent or advanced disease.

• Chemotherapy regimen in the adjuvant or neoadjuvant setting following surgery and/orradiation is acceptable if recurrent or advanced disease develops within 6 monthsfrom completion of therapy.

• Participants with a known epidermal growth factor receptor (EGFR) mutation must havereceived a chemotherapy regimen and an EGFR tyrosine kinase inhibitor (TKI) (e.g.,erlotinib, gefitinib, afatinib, or experimental)

• Participants with a known anaplastic lymphoma kinase (ALK) translocation must havereceived a chemotherapy regimen and an ALK inhibitor (e.g., crizotinib, ceritinib orexperimental) 4) Cohort F - Participants with recurrent or advanced dMMR/MSI-H solidtumors except endometrial cancers and gastrointestinal cancers, who have receivedprior systemic therapy and who have no alternative treatment options. Priortreatment with hormone therapies alone given for recurrent or advanced disease isacceptable.

• Presence of at least 1 measurable lesion by RECIST 1.1 on baseline scan will beconfirmed by central radiology review prior to first dose of dostarlimab. Patientswith primary central nervous system (CNS) tumor should provide brain MRI atbaseline.

• Presence of deficient mismatch repair (dMMR) and/or microsatellite instability (MSI-H) in the tumor defined by either: i) deficient DNA mismatch repair (dMMR); MMR status must be assessed byimmunohistochemistry (IHC) for MMR protein expression (MLH1, MSH2, MSH6, PMS2) whereloss of one or more proteins indicates dMMR; dMMR may be determined either locallyor by the central reference lab; OR ii) Microsatellite instability (MSI-H); MSI-H asdetermined by polymerase chain reaction (PCR) or by tissue NGS; MSI-H may bedetermined locally 5) Cohort G: Participants must have recurrent high-grade serous,endometrioid, or clear cell ovarian, fallopian tube, or primary peritoneal cancer.

• Participants must have presence of at least 1 measurable lesion on Baseline scanthat will be confirmed by central radiology review.

• Participants must be considered resistant to the last administered platinum therapy,that is, the time from the last administered platinum dose until the initialdocumented progression (as evidenced by radiographic progression per RECIST version 1.1) must be less than 6 months.

• Participants must have completed at least 1 but no more than 3 prior lines oftherapy for advanced or metastatic ovarian cancer. Neoadjuvant, adjuvant, and thecombination of both will be considered as 1 line of therapy. Treatment withsingle-agent bevacizumab given as maintenance is not counted as a separate line oftherapy. If a therapeutic regimen is modified or changed for a reason other thanlack of response or PD (such as allergic reaction, toxicity, or drug availability),this is not counted as a separate line of therapy. The use of single-agent hormonaltherapy given for reasons other than PD per RECIST version v1.1 (i.e., hormonaltherapy given for increasing Cancer antigen [CA]-125 levels) is not counted as aseparate line of therapy.

• Participants must have been previously treated with platinum-based regimn, taxaneagent(s), and bevacizumab (bevacizumab could be used as a single agent or incombination with another agent, in frontline therapy, as maintenance, or fortreatment of recurrent disease).

• Part 2B: Participants must have archival tumor tissue available that isformalin-fixed and paraffin-embedded (FFPE).

• For participants who do not have archival tissue, a new biopsy must be performed toobtain a tissue sample prior to study treatment initiation. For participants withoutavailable archival tissue, the biopsy should be taken from the tumor lesions (eitherprimary or metastatic) that have easy accessibility and low biopsy-associated risksand will exclude biopsies of the liver, brain, lung/mediastinum, pancreas, orendoscopic procedures extending beyond the esophagus, stomach or bowel.

• For Cohort F an FFPE tissue sample must be submitted to the central laboratory fortesting. Specimens containing bone are not acceptable. For patients with availablelocal MMR/MSI-H results, tumor samples have to be submitted to a central laboratoryand its quality has to be checked and cleared prior to C1D1

• For Cohort G, participant must provide formalin fixed paraffin embedded (FFPE) tumortissue block(s) with sufficient tumor content (as confirmed by the Sponsor'sdesignated central laboratory) during screening to enable, for example, measures ofhomologous recombination pathway defects and PD-L1 status. The use of slides createdfrom paraffin-embedded tissue as opposed to FFPE blocks must be approved by theSponsor.

• Female participants must have a negative serum pregnancy test within 72 hoursprior to the date of the first dose of study medication: unless they are ofnon-child bearing potential.Non child bearing potential is defined as:

• >= 45 years of age and has not had menses for > 1 year;

• Amenorrheic for < 2 years without a hysterectomy and oophorectomy and have afollicle- stimulating hormone (FSH) value in the postmenopausal range upon pre-study (screening) evaluation.

• Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documentedhysterectomy or oophorectomy must be confirmed with medical records of the actualprocedure or confirmed by an ultrasound, magnetic resonance imaging (MRI) orcomputed tomography (CT) scan. Tubal ligation must be confirmed with medical recordsof the actual procedure.

• Female participants of childbearing potential must agree to use 1 highlyeffective form of contraception with their partner starting with the screeningvisit through 150 days after the last dose of study therapy.

• Participant has an Eastern Cooperative Oncology Group (ECOG) performance statusof <= 2 for Part 1 and <= 1 for Part 2.

• Participant has an adequate organ function.

• Participants with known human immunodeficiency virus (HIV) infection areallowed with following requirements:

• Documented evidence of plasma HIV-1 RNA persistently <50 copies (c)/mL ≤3 monthsprior to AND at Screening. In the >3 to 12 months prior to Screening, plasma HIV-1RNA consistently <50 c/mL required; if single increases ≥50 c/mL occurred, theycannot have been persistent nor associated with antiretroviral resistance perInvestigator's assessment AND

• CD4 cell count >350 cells/mm^3 over past 12 months and at Screening (and nomeasurement ≤200 cells/mm3 during that time period) AND

• Must be on an uninterrupted combination antiretroviral therapy regimen for at least 3 months prior to Screening, with combination antiretroviral therapy regimenconsistent with locally recommended guidelines

• Participants with history of Centers for Disease Control and Prevention (CDC)Stage 3 disease (CDC, 2014; also known as acquired immunodeficiency syndrome [AIDS]- defining disease) are allowed if AIDS-defining disease has been treatedand cured or is stable for ≥3 months prior to study entry. Cutaneous Kaposi'sSarcoma not requiring systemic therapy is allowed.

• No history of HIV-associated non-Hodgkin lymphoma ≤5 years prior to study andno history of HIV-associated invasive cervical cancer

• No treatment with an HIV-1 immunotherapeutic vaccine within 90 days ofScreening.

Exclusion Criteria:

• Participant has received prior therapy with an anti- programmed death receptor 1 (anti-PD-1), anti-PD-1- ligand-1 (anti-PD-L1), or anti-PD-1 ligand-2 (anti-PD- L2)agent.

• Participant has a known uncontrolled CNS metastasis and/or carcinomatous meningitis.

• Participant has a known additional malignancy that progressed or required activetreatment within the last 2 years. Exceptions include basal cell carcinoma of theskin, squamous cell cancer (SqCC) of the skin that has undergone potentiallycurative therapy, or in situ cervical cancer, or other neoplastic condition whichhas undergone curative therapy and is considered cured by the investigator.

• Participant is considered a poor medical risk due to a serious, uncontrolled medicaldisorder, nonmalignant systemic disease or active infection requiring systemictherapy. Specific examples include, but are not limited to, active, non-infectiouspneumonitis; uncontrolled ventricular arrhythmia; recent (within 90 days) myocardialinfarction; uncontrolled major seizure disorder; unstable spinal cord compression;superior vena cava syndrome; or any psychiatric or substance abuse disorders thatwould interfere with cooperation with the requirements of the study (includingobtaining informed consent).

• Participant is pregnant or breastfeeding or expecting to conceive children withinthe projected duration of the study, starting with the Screening Visit through 150days after the last dose of study treatment.

• Participant has a diagnosis of immunodeficiency or is receiving systemic steroidtherapy or any other form of immunosuppressive therapy within 7 days prior to thefirst dose of study treatment.

• Participant has a documented presence of hepatitis B surface antigen [HBsAg] atscreening or within 3 months prior to the first dose of study intervention.Participants with a negative HbsAg and positive hepatitis B virus core antibody (HBcAb) result are eligible only if HBV DNA is negative.

• Participant has an active autoimmune disease that has required systemic treatment inthe past 2 years (i.e., with use of disease- modifying agents, corticosteroids, orimmunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, orphysiologic corticosteroid replacement therapy for adrenal or pituitaryinsufficiency, etc.) is not considered a form of systemic treatment. Use of inhaledsteroids, local injection of steroids, and steroid eye drops are allowed.

• Participant has as history of interstitial lung disease.

• Participant has not recovered (i.e., to <= Grade 1 or to Baseline) from radiation-and chemotherapy-induced AEs or received transfusion of blood products (includingplatelets or red blood cells) or administration of colony-stimulating factors (including granulocyte-colony stimulating factor [G-CSF], granulocyte macrophagecolony-stimulating factor [GM-CSF] or recombinant erythropoietin) within 3 weeksprior to the first dose of study drug.

• Participant has participated in a study of an investigational agent and receivedstudy therapy or used an investigational device within 4 weeks prior to the firstdose of study drug.

• Participant has received prior anticancer therapy (chemotherapy, targeted therapies,radiotherapy, or immunotherapy) within 21 days prior to study Day 1

• Participant has not recovered adequately (<= Grade 1) from AEs and/or complicationsfrom any major surgery prior to starting therapy.

• Participant has received a live vaccine within 14 days of planned start of studytherapy.

• Participant has a known hypersensitivity to dostarlimab components or excipients.

• For Cohort G, participants will not be eligible if they meet the following criteria:

• Participants who experienced disease progression within 3 months (as evidencedby radiographic progression per RECIST) of first-line platinum therapy.

• Participants with known deleterious or suspicious deleterious mutation in BRCA1or BRCA2 genes (local testing permitted).

• Participants has received prior therapy with a poly(adenosinediphosphate-ribose) polymerase (PARP)-1/PARP-2 inhibitor.

• Participant has a history or current evidence of any condition, therapy, orlaboratory abnormality that might confound the results of the study, mightinterfere with the participant's participation for the full duration of thestudy treatment, or is not in the best interest of the participant toparticipate.

• Participant is immunocompromised. Participants with splenectomy are allowed.