A Study of BI-1206 in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors

Inclusion Criteria:

• Is willing and able to provide written informed consent for the trial.

• Is ≥18 years of age on day of signing informed consent.

• Phase I only: Has a histologically confirmed advanced solid tumor. Subjects musthave received at least 2 doses of an approved anti-PD-1/L1 mAb, and have documentedprogression on or within 12 weeks from the last dose of anti-PD-1/L1 mAb.

• For patients with NSCLC (phase 2A SC cohorts):

Have a histologically confirmed diagnosis of advanced or metastatic NSCLC and not have an EGFR sensitizing (activating) mutation or an ALK translocation.

Have a PD-L1 positive (TPS≥50%) tumor as determined by IHC at a local laboratory.

Have not received prior systemic immunotherapy or chemotherapy treatment for their advanced/metastatic NSCLC.

Have provided formalin-fixed tumor tissue sample from a biopsy of a tumor lesion either at the time of or after the diagnosis of advanced or metastatic disease has been made and from a lesion not previously irradiated to perform biomarker analysis.

• For patients with uveal melanoma (phase 2A SC cohort): Have a histologically confirmed diagnosis of advanced or metastatic uveal melanoma

Have a PD-L1 positive (TPS≥1%) tumor as determined by IHC at a local laboratory.

Have not received prior systemic immunotherapy or chemotherapy treatment for their advanced/metastatic uveal melanoma. Subjects who have received previous treatment with tebentafusp and/or liver directed therapy are allowed.

Have provided formalin-fixed tumor tissue sample from a biopsy of a tumor lesion either at the time of or after the diagnosis of advanced or metastatic disease has been made and from a site not previously irradiated to perform biomarker analysis.

• Phase I only: Is intolerant of, refuses, or is not eligible for standardantineoplastic therapy.

• Has at least 1 measurable disease lesion as defined by Response Evaluation Criteriain Solid Tumors (RECIST v1.1)

• Phase IIa only: Is willing to provide an archival tumor tissue sample or newlyobtained [core, incisional, OR excisional] biopsy of a tumor lesion not previouslyirradiated.

• Is able to safely undergo a baseline tumor tissue biopsy prior to first dose ofBI-1206.

• Has a life expectancy of ≥12 weeks.

• Has an ECOG performance status of 0-1.

• Has adequate organ function as confirmed by laboratory values listed in the mainbody of the protocol

• Phase IIa only: Participants who are HBsAg positive are eligible if they havereceived HBV antiviral therapy for at least 4 weeks and have undetectable HBV viralload prior to enrolment

• Phase IIa only: Participants with history of HCV infection are eligible if HCV viralload is undetectable at Screening

• Phase IIa only: Has adequate hematological and biochemical indices as listed in themain body of the protocol

Exclusion Criteria:

• Needs doses of prednisolone >10 mg daily (or equipotent doses of othercorticosteroids) while on the study, other than as premedication.

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

• Has known or suspected hypersensitivity to pembrolizumab or BI-1206 or any of theirexcipients.

• Has cardiac or renal amyloid light-chain (AL) amyloidosis.

• Has received radiotherapy within 2 weeks of the first dose of BI-1206.

• Has not recovered from AEs to at least Grade 1 by CTCAE v5.0 (or higher) due toprior anticancer therapies• Has a history of (non-infectious) pneumonitis thatrequired steroids or has current pneumonitis

• Has an active, known or suspected autoimmune disease.

• Is a female subject and has the ability to become pregnant (or already pregnant orlactating/breastfeeding)

• Is a male subject with partner(s) of childbearing potential (unless he agrees to usea barrier method of contraception during the study and for 12 months aftercompleting treatment)

• Has had major surgery from which the subject has not yet recovered Is at highmedical risk because of non-malignant systemic disease, including severe activeinfections on treatment with antibiotics, antifungals, or antivirals

• Has presence of chronic graft-versus-host disease.

• Has had an allogenic tissue/solid organ transplant.

• Has a known history of HIV infection

• Has a history of active tuberculosis (Bacillus tuberculosis)

• Has received a live vaccine within 30 days before the first dose of study treatment

• Has uncontrolled or significant cardiovascular disease as listed in the main body ofthe protocol

• Has a known psychiatric or substance abuse disorder that would interfere with thesubject's ability to cooperate with the requirements of the study

• Has a history or current evidence of any condition, therapy, or laboratoryabnormality that might confound the results of the study, interfere with thesubject's participation for the full duration of the study, or lead to participationnot being in the best interest of the subject, in the opinion of the treatingInvestigator.

• Is participating or planning to participate in another interventional clinical studyor has participated in a study of an investigational agent or has used aninvestigational device within 4 weeks prior to the first dose of study drug

• Has a known additional malignancy of another type, with the exception of adequatelytreated cone-biopsied carcinoma in situ (e.g., breast carcinoma, cervical cancer insitu) and basal or squamous cell carcinoma of the skin

• Has a diagnosis of primary or acquired immunodeficiency disorder or has taken anyother form of immunosuppressive therapy within 7 days prior to the first dose ofstudy drug.

• Is unable to attend the study site to receive the study treatment

Additional exclusion criteria are described in the protocol.