Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)

Select Inclusion Criteria:

• Males or females aged ≥18 years.

• Parts 1 and 3 (escalation cohorts): Subjects with locally advanced or metastatic nonresectable solid tumors, whose disease has progressed despite all standard therapiesor for whom no further standard or clinically acceptable therapy exists.

• Part 2 (single-agent expansion cohort): Subjects with NSCLC, melanoma, HNSCC, G/GEA,RCC, or TCC, with histologically confirmed, locally advanced or metastatic,non-resectable disease, which has progressed despite all standard therapiesincluding CPI or for whom no standard or clinically acceptable therapy exists.

• Part 4 (expansion cohorts in combination with pembrolizumab, with or withoutchemotherapy): Subjects with melanoma (all types), HNSCC, G/GEA, RCC, TCC, NSCLC, orMSI-high, TMB-high, MMR-deficient tumors, with histologically confirmed, locallyadvanced or metastatic, non resectable disease, which is either CPI-naive (melanoma,HNSCC, NPC) or progressed despite all standard therapies including CPI (NSCLC, RCC,TCC, uveal melanoma, MSI-high, TMB-high, or MMR-deficient solid tumors) or for whomno standard or clinically acceptable therapy exists.

• For Cohort F3 (NSCLC), subjects may have progressed on no more than 2 lines ofstandard therapy that must include at least one PD-1/L1 regimen.

• For Cohort F4 (HNSCC and NPC), subjects may be previously treated with no more than 1 prior chemotherapy regimen in metastatic setting. Prior PD-1/L1 in curative (neo-adjuvant/adjuvant) setting is allowed only if completed >/= 6 months prior toprogression to local recurrence or metastatic disease.

• All subjects with non-squamous NSCLC must have documentation of absence of tumoractivating EGFR mutations and absence of ALK gene rearrangements.

• PD-L1 by IHC (22C3): Parts 1 and 3: IHC optional. Part 2: IHC result mandatory butany score allowed. Combined Positive Score (CPS) ≥ 1% (or Tumor Proportion Score ≥50% for NSCLC; for TMB-high tumors, any TPS% is allowed). Part 4: Combined PositiveScore (CPS) ≥ 1% (or Tumor Proportion Score ≥50% for NSCLC; for TMB-high tumors, anyTPS% is allowed).

• Adequate hematologic, coagulation, hepatic and renal function and ECOG score asdefined per protocol.

Select Exclusion Criteria:

• Prior exposure to OX40 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 withcertain exceptions.

• Hematologic malignancies (e.g., ALL, AML, MDS, CLL, CML, NHL, Hodgkin's 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-106.

• Known active central nervous system (CNS) metastases and/or carcinomatousmeningitis. Exception: Subjects who are previously treated and are radiologicallyand clinically stable without the requirement for steroid treatment for at least 14days prior to first dose of study treatment may be allowed study entry if certaincriteria apply.

• 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.

• Diagnosis of immunodeficiency or treatment with systemic immunosuppressivemedications within 7 days prior to the first dose of study drug. Certain exceptionsas defined in protocol apply.

• History of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV)infection. Exceptions as defined in protocol 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; or oxygen saturation <92% on room air.

• 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.

• Additional in- and exclusion criteria per protocol.