Study of INBRX-105 and INBRX-105 With Pembrolizumab in Patients With Solid Tumors Including Head and Neck Cancer

Inclusion Criteria:

• Parts 1 and 3 (escalation cohorts; completed): Patients with locally advanced ormetastatic non-resectable solid tumors, whose disease has progressed despitestandard therapy and for whom no further standard therapy exists.

• Part 2 (expansion cohorts): Patients with non-small cell lung cancer, cutaneousmelanoma, head and neck squamous cell carcinoma or solid tumors amenable to pairedbiopsies, with locally advanced or metastatic, non-resectable disease, which hasprogressed despite standard therapy or for whom no standard or clinically acceptabletherapy exists.

• Part 4 relapsed or refractory to CPI cohorts: NSCLC, cutaneous melanoma, HNSCC,MSI/TMB-high or MMRd solid tumors

• Part 4 CPI naive cohorts: locally advanced or metastatic, non-resectable NSCLC orHNSCC

• Refractory or relapsed to anti-PD-1 or anti-PD-L1, and anti-CTLA4 if applicable (NOTE: For all tumor types with checkpoint inhibitor approvals) with exception ofthe treatment naive NSCLC cohort.

• PD-L1 positivity by immunohistochemistry (IHC): Parts 1 and 3 (escalation cohorts)PD-L1 positivity is not required. Parts 2 and 4 (expansion cohorts): CombinedPositive Score (CPS) or Tumor Proportion Score (TPS) above certain thresholds asdefined per protocol.

• Adequate hematologic, coagulation, hepatic and renal function as defined perprotocol.

• Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.

Exclusion Criteria:

• Prior exposure to 4-1BB agonists.

• Receipt of any investigational product or any approved anticancer drug(s) orbiological product(s) within 4 weeks prior to the first dose of study drug.Exceptions: Hormone replacement therapy, testosterone, or oral contraceptives. NOTE:Previous exposure to anti-PD-L1 checkpoint inhibitor requires a minimum washoutperiod of 24 weeks prior to the first dose of study drug.

• Hematologic malignancies (e.g., ALL, AML, MDS, CLL, CML, NHL, Hodgkin lymphoma andmultiple myeloma).

• Prior or concurrent malignancies. Exception: Subjects with a prior or concurrentmalignancy whose natural history or treatment does not have the potential tointerfere with the safety or efficacy assessments of INBRX-105.

• Known or active primary central nervous system (CNS) tumors, leptomeningeal diseaseand CNS metastases. Exception: Subjects with previously treated, asymptomatic, andclinically stable CNS metastases may be allowed study entry if certain criteriaapply.

• Grade ≥ 3 immune-related adverse events (irAEs) or irAE that lead to discontinuationof prior immunotherapy. Some exceptions as defined per protocol apply.

• Active autoimmune disease or documented history of autoimmune disease that requiredsystemic steroids or other immunosuppressive medications. Certain exceptions asdefined in protocol apply.

• Treatment with systemic immunosuppressive medications within 4 weeks prior to thefirst dose of study drug. Certain exceptions as defined in protocol apply.

• History of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).Exceptions as defined in protocol for expansion cohorts will apply.

• History of hepatitis or cirrhosis (e.g., non-alcohol steatohepatitis, alcohol ordrug-related, autoimmune, hepatitis B, or hepatitis C). Exceptions as defined inprotocol for expansion cohorts will apply.

• Active interstitial lung disease (ILD) or pneumonitis or a history of ILD orpneumonitis requiring treatment with steroids or other immunosuppressivemedications.

• Clinically significant cardiac condition, including myocardial infarction,uncontrolled angina, cerebrovascular accident, or other acute uncontrolled heartdisease < 3 months; left ventricular ejection fraction (LVEF) < 50%; New York HeartAssociation (NYHA) Class III or IV congestive heart failure; or uncontrolledhypertension.

• Active, hemodynamically significant pulmonary embolism within 3 months prior toenrollment on this trial.

• Major surgery within 4 weeks prior to enrollment on this trial.

• Anti-infectious drug treatments (i.e., antibiotics) within 4 weeks prior to thefirst dose of study drug.

• Prior organ allograft transplantations or allogeneic peripheral blood stem cell (PBSC) or bone marrow (BM) transplantation.