A Study of TSR-022 in Participants With Advanced Solid Tumors (AMBER)

Inclusion Criteria

• Participant is at least 18 years of age.

• Female participants of childbearing potential must have a negative serum or urinepregnancy test within 72 hours prior to the date of the first dose of studymedication or be of non-childbearing potential.

• Participant has an ECOG performance status of less than or equal to (<=)1.

• Participant has adequate organ function.

Inclusion Criteria for Participants in Part 1 and Part 2 Cohorts A, B, and C:

• Participant with advanced or metastatic solid tumor who meets the requirements forthe part of the study/cohort he/she will participate in, as follows:

• Part 2: Histologically proven advanced (unresectable) or metastatic solid tumor thatis measurable by computed tomography (CT) or magnetic resonance imaging (MRI) perRECIST version 1.1 criteria Inclusion Criteria for Participants in Part 2 Cohort D

• Participants with advanced or metastatic non-small cell lung carcinoma (NSCLC) thatis measurable by CT or MRI per RECIST version 1.1 criteria and meet the followingcriteria:

• NSCLC histology includes squamous or non-squamous cell carcinoma.

• Participants have received no more than 2 prior lines of therapy, which must includea platinum-based chemotherapy (for example [e.g.], cisplatin, carboplatin) and ananti- programmed death-ligand 1 (PD-L1) antibody.

• Participants must have documented radiographic progression by RECIST version 1.1criteria on prior anti-programmed cell death protein (PD-1) or anti-PD-L1 therapy.

• Biopsies -All participants enrolled must undergo a biopsy prior to study entry, andthe biopsy tissue must be submitted to the central laboratory for all participantsin order to determine T-cell immunoglobulin and mucin-domain containing-3 (TIM-3)expression level prior to first dose. If a participant has had a biopsy prior toentering the 35-day screening period and within approximately 12 weeks of studytreatment, that biopsy may be accepted as the Baseline fresh biopsy.

Inclusion Criteria for Participants in Part 2 Cohort E

• Participant is greater than or equal to (>=)18 years old, is able to understand thestudy procedures, and agrees to participate in the study by providing writteninformed consent which includes compliance with the requirements and restrictionslisted in the Informed consent form (ICF) and protocol.

• Participant has histologically or cytologically proven advanced or metastatic NSCLC,and only squamous or non-squamous cell carcinoma.

• Participant has received no more than 2 prior lines of therapy for advanced ormetastatic disease, which must only include a platinum-based (eg, cisplatin,carboplatin) doublet chemotherapy regimen and an anti-PD-1 or anti-PD-L1 antibody (no other biologic agents alone or in combination; novel combinations are notallowed). Participants previously treated with targeted therapies, includingangiogenesis inhibitors (eg, bevacizumab, ramucirumab, lenvatinib), are noteligible.

• Participant has measurable disease, that is, presenting with at least 1 measurablelesion per RECIST v1.1 as determined by the local site Investigator/radiologyassessment. Target lesions situated in a previously irradiated area are consideredmeasurable if disease progression has been demonstrated in such lesions and if thereare other target lesions. If there is only 1 target lesion that was previouslyirradiated, the participant is not eligible.

• Participant has documented radiological disease progression on prior platinum-basedchemotherapy and on prior anti-PD-1 or anti-PD-L1 therapy according to RECIST v1.1.

• Participant agrees to submit an archival formalin fixed paraffin embedded (FFPE)tumor tissue specimen that was collected on or after diagnosis of metastatic diseasefrom location(s) not irradiated prior to biopsy. Both tissue block and freshly cutslides are acceptable. If archival tissue is not available, the participant mustundergo biopsy prior to study entry.

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

• Participant has a life expectancy of at least 3 months and is anticipated to be ableto complete 4 cycles of docetaxel treatment.

• Participant has adequate organ function as defined in the protocol

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

Inclusion Criteria for Participants in Part 2 Cohort F

• Histologically confirmed locally advanced or metastatic and/or unresectableHepatocellcular Carcinoma (HCC)

• Barcelona Clinic Liver Cancer Stage B or C

• Cirrhosis grade of Child-Pugh Class A

• No prior systemic therapy for HCC

• Documented HBV testing at screening, including hepatitis B surface antigen (HBsAg),hepatitis B surface antibody (HBsAB) and hepatitis B core antibody (HBcAb).Participants with a positive HBsAg will require negative hepatitis B virus (HBV) DNAtesting at screening.

• Participants with chronic HBV infection (HBsAg +) are required to be receivingeffective antiviral therapy (i.e., with Tenofovir or Entecavir) for at least 14days with willingness to continue for the length of the study and have HBVdeoxyribonucleic acid (DNA) less than 100 International Units Per Milliliter (IU/mL) within 28 days prior to initiation of study treatment.

• Participants with chronic HBV infection (HBsAg+) require documented Hepatitis Dvirus (HDV) antibody testing conducted at screening. If HDV antibody ispositive, then HDV ribonucleic acid (RNA) must be negative to participate.

• Participants with a negative HBsAg and positive HBcAb result are eligible onlyif HBV DNA is negative (Past HBV participants).

• Documented hepatitis C virus (HCV) antibody testing conducted at screening. If HCVantibody is positive, then HCV RNA must be negative. Participants with recentlytreated HCV prior to study start must be greater than (>)12 weeks from final HCVtreatment.

• Must have measurable disease, defined as at least one tumor lesion that can beaccurately measured according to RECIST v1.1

• Participant agrees to submit an archival FFPE tumor tissue specimen that wascollected on or after diagnosis of metastatic disease from location(s) notirradiated prior to biopsy. Both tissue block and freshly cut slides are acceptable.If archival tissue is not available, the participant must undergo biopsy prior tostudy entry.

• Participants are also encouraged, but not required, to have a fresh tumor tissuebiopsy of a primary or metastatic tumor prior to dosing (samples will be used toenable biomarker analysis).

• International normalized ratio (INR) or prothrombin time (PT) <= 2× upper limit ofnormal (ULN) unless participant is receiving anticoagulant therapy as long as PT orpartial thromboplastin (PTT) is within therapeutic range of intended use ofanticoagulants. Activated partial thromboplastin time (aPTT) <=2×ULN unlessparticipant is receiving anticoagulant therapy as long as PT or PTT is withintherapeutic range of intended use of anticoagulants

• Negative human immunodeficiency virus (HIV) test at screening The Investigator isresponsible for review of medical history, menstrual history, and recent sexualactivity to decrease the risk for inclusion of a woman with an early undetectedpregnancy.

Exclusion criteria:

• History of Grade greater than or equal to (>=)3 immune-related AE with priorimmunotherapy, with the exception of non-clinically significant lab abnormalities.

• Participant has known uncontrolled central nervous system (CNS) metastases and/orcarcinomatous meningitis.

• Participant has a known additional malignancy that progressed or required activetreatment within the last 2 years. Participants with a prior or concurrentmalignancy whose natural history or treatment does not have the potential tointerfere with the safety or efficacy assessment of the investigational regimen maybe included only after discussion with the Medical Monitor.

• Participant is considered a poor medical risk due to a serious, uncontrolled medicaldisorder, non-malignant systemic disease or active infection requiring systemictherapy.

• 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.

Exclusion Criteria for Participants in Part 2 Cohort D

• A participant with negative (as determined by Central Testing Lab) or unevaluableTIM-3 expression from tissue obtained prior to study entry will not be eligible forthe study.

• Participant has received prior therapy as defined below:

• Prior treatment with anti-PD-1, anti-PD-L1, or anti-PD-L2 agent that resulted inpermanent discontinuation due to an AE.

• Prior treatment with an anti-lymphocyte activation gene (LAG)-3 or anti-TIM-3.

• Radiologic or clinical progression <= 8 weeks after initiation of prior anti-PD-1 oranti-PD-L1 antibody.

• Participants with known epidermal growth factor receptor (EGFR) mutation, anaplasticlymphoma kinase (ALK) translocation, or receptor tyrosine kinase (ROS1) mutation.

• Participant has received a vaccine other than a vaccine against severe acuterespiratory syndrome (SARS)-coronavirus 2 (CoV-2) infection ("Coronavirus Disease 2019" [COVID-19]) within 7 days of planned start of study therapy. The use of allCOVID-19 vaccines is allowed, with the exception of COVID-19 vaccines using therecombinant adenoviral vector platform within 30 days of planned start of studytherapy. If a COVID-19 vaccine using this platform is to be administered within 30days of planned start of study therapy, this must first be discussed with andapproved by the Sponsor's Medical Monitor.

Exclusion Criteria for Participants in Part 2 Cohort E

• Participant has been previously treated with an anti PD 1, anti PD L1, or anti PD L2agent that resulted in permanent discontinuation due to an AE

• Participant has been previously treated with an anti TIM-3 or anti cytotoxic Tlymphocyte-associated protein 4 (CTLA 4) agent or docetaxel.

• Participant has a documented sensitizing EGFR, ALK, or ROS-1 mutation. Participantswhose tumors have not been tested for these driver mutations and therefore who haveunknown driver mutation status are not eligible. Participants with squamoushistology do not need to be tested for these driver mutations.

• Participant had radiological or clinical disease progression (that is [ie,]worsening performance status, clinical symptoms, and laboratory data) <=8 weeksafter initiation of prior anti PD 1 or anti-PD-L1 antibody. The clinical diseaseprogression should have been confirmed by a subsequent radiological scan.

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

• Participant has completed palliative radiotherapy within 7 days prior to the firstdose of study treatment.

• 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 new or progressive brain metastases and/or leptomeningealmetastases. Participants who have received prior therapy for their brain metastasesand have radiologically stable central nervous system disease may participate,provided they are neurologically stable for at least 4 weeks before study entry andare off corticosteroids within 3 days prior to the first dose of study treatment.

• Participant has tested positive for the following at Screening or within 3 monthsbefore the first dose of study treatment:

• Presence of hepatitis B surface antigen.

• Presence of hepatitis C antibody in the absence of an Ribonucleic acid (RNA) testfor hepatitis C virus.

• 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 (eg, thyroxine,insulin, or physiologic corticosteroid replacement therapy of prednisone, orequivalent, for adrenal or pituitary insufficiency) is not considered a form ofsystemic 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 current interstitial lung disease, current pneumonitis, or a historyof pneumonitis that required the use of glucocorticoids to assist with management.Lymphangitic spread of the NSCLC is not exclusionary.

• Participant does not meet requirements per local prescribing guidelines forreceiving treatment with docetaxel, including severe hypersensitivity reactions todrugs formulated with polysorbate 80.

• Participant has received prior anticancer therapy (chemotherapy, targeted therapies,radiotherapy, or immunotherapy) within 21 days, or less than 5 times the half lifeof the most recent therapy prior to study Day 1, whichever is shorter.

Exclusion Criteria for Participants in Part 2 Cohort F

• Known fibrolamellar HCC, sarcomatoid HCC or mixed cholangiocarcinoma and HCC

• Participant must not have had major surgery <= 3 weeks prior to initiating protocoltherapy and participant must have recovered from any surgical effects

• Participants must not have received investigational therapy <= 4 weeks, or within atime interval less than at least 5 half-lives of the investigational agent,whichever is shorter, prior to initiating protocol therapy.

• Active or untreated central nervous system (CNS) and leptomeningeal metastases

• Prior therapy with any medication targeting PD-1, PD-L1, or TIM-3

• Participant must not have a known hypersensitivity to TSR-042 and TSR-022 componentsor excipients.

• Participants with active malignancy (other than HCC) or a prior malignancy withinthe past 2 years are excluded. Participants with completely resected cutaneousmelanoma (early stage), basal cell carcinoma, cutaneous squamous cell carcinoma,cervical carcinoma in-situ, breast carcinoma in-situ, and localized prostate cancerare eligible

• Participant must not have serious, uncontrolled medical disorder, or nonmalignantsystemic disease as determined by the treating physician. Examples include, but arenot limited to uncontrolled ventricular arrhythmia, uncontrolled major seizuredisorder, unstable spinal cord compression, or superior vena cava syndrome.

• Has a history or evidence of cardiac abnormalities within the 6 months prior toenrollment, including:

• Serious, uncontrolled cardiac arrhythmia or clinically significant ECGabnormalities including second-degree (Type II) or third-degreeatrioventricular (AV) block.

• Cardiomyopathy, myocarditis, myocardial infarction, acute coronary syndromes (including angina pectoris), coronary angioplasty, stenting, or bypassgrafting.

• Congestive heart failure [New York Heart Association (NYHA) Class III or IV]

• Symptomatic pericarditis

• Known history of HIV infection

• Active tuberculosis infection or other microbial infection or any active systemicinfection requiring parenteral antibiotic therapy. All prior infections must haveresolved following optimal therapy.

• 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.

• History of idiopathic pulmonary fibrosis, interstitial lung disease, bronchialasthma, organizing pneumonia, bronchiolitis obliterans, drug-induced pneumonitis, oridiopathic pneumonitis

• History of organ transplantation including allogeneic bone marrow transplantation

• Participant has a diagnosis of immunodeficiency or has been receiving systemicsteroid therapy or any other form of immunosuppressive therapy within 7 days priorto initiating protocol therapy.

• Participant has received a live vaccine within 7 days of initiating protocoltherapy. Seasonal flu vaccines that do not contain live virus and COVID 19 vaccinesare permitted.

• Psychiatric illness/social situations that would limit compliance with studyrequirements

• Pregnant, lactating, breastfeeding, or intending to become pregnant during the studyand for 150 days after the study