S095035 as a Single Agent and in Combination in Adult Participants With Advanced or Metastatic Solid Tumors With Deletion of MTAP

Inclusion Criteria:

• Estimated life expectancy ≥3 months.

• ECOG PS 0-1

• Participants able to comply with highly effective method of birth controlrequirements.

• Participants with histologically confirmed advanced or metastatic solid tumor's (excluding central nervous system tumors other than IDHwt glioblastoma), withmeasurable disease as per RECIST 1.1 or RANO 2.0 criteria for participants withIDHwt glioblastoma, that have progressed after at least one prior treatment regimengiven for advanced/metastatic disease, and for whom additional effective standardtherapy is not available. Patients in China with IDHwt glioblastoma will not beincluded.

• Participants with pre-existing documented MTAP homozygous gene deletion in theirtumor tissue, determined using a next generation sequencing in vitro diagnostic testprior to screening.

• Phase 1 only - Participants (except IDHwt glioblastoma) willing to undergo pairedfresh biopsy (pre-treatment and on-treatment) procedure. Exceptions may be made forfeasibility and safety concerns. IDHwt glioblastoma must provide archival tissuefrom most recent surgery or biopsy.

• Adequate organ functions.

• Phase 2 only - Participants in dose expansion, except those with IDHwt glioblastoma,must provide newly collected tumor biopsies at screening. If not medically feasiblearchival tissue may be used, provided it was collected within 3 months before studyentry and no treatment has been received since the most recent biopsy.

• Phase 2 only - Participants with IDHwt glioblastoma must provide archival tissuefrom their most recent surgery or biopsy, collected before screening.

• Phase 2 only - Participants in China who are to be considered for enrollment in thesingle agent dose expansion Arms and who have a pre-existing, documentedcyclin-dependent kinase inhibitor 2A (CDKN2A) homozygous gene deletion in theirtumor tissue (confirmed by an NGS IVD test), but do not have homozygous MTAPdeletion reported, will need to be pre-screened to confirm homozygous MTAP deletion.Pre screening for homozygous MTAP deletion will be conducted using a central NGS IVDtest using an archival tumor tissue, preferably the most recent and not older than 3years.

• Phase 2 Arm 1a only - Participants with histologically or cytologically confirmedmetastatic or unresectable locally advanced NSCLC with homozygous deletion of MTAP,with measurable disease as per RECIST version 1.1, who have progressed orexperienced disease recurrence during or after at least 1 prior line ofstandard-of-care systemic therapy in the advanced/metastatic setting.

• Phase 2 Arm 1b only - Participants with histologically or cytologically confirmedmetastatic or unresectable locally advanced BTC with homozygous deletion of MTAP,who have progressed or experienced disease recurrence during or after at least 1prior line of standard-of-care systemic therapy in the advanced/metastatic setting.

• Phase 2 Arm 1c only - Participants with histologically or cytologically confirmedmetastatic or unresectable locally advanced PDAC with homozygous deletion of MTAP,who have progressed or experienced disease recurrence during or after at least 1prior line of standard-of-care systemic therapy in the advanced/metastatic setting.

• Phase 2 Arm 1d only - Participants with any other locally advanced or metastaticmalignancies with homozygous deletion of MTAP, who have received and progressed ofexperienced recurrence during or after receiving at least 1 prior line ofstandard-of-care systemic therapy in the advanced/metastatic setting.

• Phase 2 Arm 2a only - Participants with histologically or cytologically confirmedmetastatic or unresectable locally advanced BTC with homozygous deletion of MTAP,who have progressed or experienced disease recurrence during or after receiving atleast 1 prior line of standard-of care systemic therapy in the advanced/metastaticsetting.

• Phase 2 Arm 2b only - Participants with histologically or cytologically confirmedmetastatic or unresectable locally advanced gastroesophageal cancer with homozygousdeletion of MTAP, who have progressed or experienced disease recurrence during orafter receiving at least 1 prior line of standard-of-care systemic therapy in theadvanced/metastatic setting.

• Phase 2 Arm 2c only - Participants with histologically or cytologically confirmedmetastatic or unresectable locally advanced PDAC with homozygous deletion of MTAP,who have progressed or experienced disease recurrence during or after receiving atleast 1 prior line of standard-of-care systemic therapy in the advanced/metastaticsetting.

Exclusion Criteria:

• Inability to take an orally administered drug, or medical disorder or prior surgicalresection that may affect the absorption of the study drug.

• Active second primary malignancy other than non-melanoma skin cancers, nonmetastaticprostate cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of thebreast, or other malignancy that the Sponsor's Medical monitor and investigatoragree and document that it should not be exclusionary.

• Known prior severe hypersensitivity to any component of the study drug formulation.

• Major surgery within 4 weeks prior to the first study drug administration orparticipants who have not recovered from side effects of the surgery.

• Have a known history of Gilbert's syndrome.

• Participants with a known clinically significant cardiovascular disease orcondition.

• Participants with thrombosis, or a history of deep vein thrombosis or pulmonaryembolism, within 4 weeks prior to first IMP administration.

• Active brain metastases.

• Participants who have received systemic anticancer treatment or radiotherapy lessthan 2 weeks before the first dose of study drug

• Pregnant or lactating women.

• Women of childbearing potential who have a positive pregnancy test within 7 daysprior to the first day of study drug administration.

• History of gastrointestinal perforation and /or fistula or aorto-esophageal fistulawithin 6 months prior to first study drug intake.

• Severe or uncontrolled active acute or chronic infection.

• Participants who have already received a MAT2A or PRMT5 inhibitor.

• A medical condition that results in increased clinically significantphotosensitivity (e.g., solar urticaria, lupus erythematosus, etc.).

• Participants who are scheduled to receive the S095035-TNG462 combination, with aknown clinically significant ophthalmologic disease, including:

• Prior history of drug-induced or toxic retinopathy or optic neuropathy

• Uncontrolled glaucoma

• Pre-existing macular degeneration

• Ongoing Grade ≥2 retinopathy, optic neuropathy, or optic neuritis

• Other known active retinal pathology