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

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Frequency of adverse events of INBRX-106 as single agent and in combination with pembrolizumab

Primary Outcome 1 - Timeframe: ~2 years

Primary Outcome 2 - Measure: Severity of adverse events of INBRX-106 as single agent and in combination with pembrolizumab

Primary Outcome 2 - Timeframe: ~2 years

Primary Outcome 3 - Measure: MTD and/or RP2D of INBRX-106 as single agent and in combination with pembrolizumab

Primary Outcome 3 - Timeframe: ~2 years

Primary Outcome 4 - Measure: Antitumor activity of INBRX-106 in combination with pembrolizumab in expansion cohorts

Primary Outcome 4 - Timeframe: ~2 years

Primary Outcome 5 - Measure: Frequency and severity of adverse events of INBRX-106 in combination with pembrolizumab and chemotherapy in adults with locally advanced or metastatic NSCLC or resectable Stage II

Primary Outcome 5 - Timeframe: ~2 years

Primary Outcome 6 - Measure: IIIA or IIIB (T3-4N2) NSCLC

Primary Outcome 6 - Timeframe: ~2 years

Primary Outcome 7 - Measure: To assess the antitumor activity of INBRX-106 in combination with pembrolizumab and platinum doublet chemotherapy as neoadjuvant/adjuvant therapy in adult subjects with NSCLC. (Cohort F8)

Primary Outcome 7 - Timeframe: N/A

CONDITION

• Solid Tumor
• Non-Small Cell Lung Cancer
• Head and Neck Cancer
• Melanoma
• Gastric Cancer
• Renal Cell Carcinoma
• Urothelial Carcinoma
• Resectable Non-Small-Cell Lung Cancer

ELIGIBILITY

Select Inclusion Criteria:
* Males or females aged ≥18 years.

- * Parts 1 and 3 (escalation cohorts): Subjects with locally advanced or metastatic non resectable solid tumors, whose disease has progressed despite all standard therapies or 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 therapies including CPI or for whom no standard or clinically acceptable therapy exists.

- * Part 4 (expansion cohorts in combination with pembrolizumab, with or without chemotherapy): Subjects with melanoma (all types), HNSCC, G/GEA, RCC, TCC, NSCLC, or MSI-high, TMB-high, MMR-deficient tumors, with histologically confirmed, locally advanced 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 whom no standard or clinically acceptable therapy exists.

- * For Cohort F3 (NSCLC), subjects may have progressed on no more than 2 lines of standard 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 to progression to local recurrence or metastatic disease.

- * For Cohort F8, subjects must have previously untreated, histologically confirmed Stage II, IIIA or IIIB (T3-4N2) NSCLC. Lymph node disease requires histologic confirmation, while T3 disease requires only radiographic documentation. Subjects need to be able to undergo planned surgery.

- * All subjects with non-squamous NSCLC must have documentation of absence of tumor activating EGFR mutations and absence of ALK gene rearrangements.

- * PD-L1 by IHC (22C3): Parts 1 and 3: IHC optional. Part 2: IHC result mandatory but any 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 Positive Score (CPS) ≥ 1% (or Tumor Proportion Score ≥50% for NSCLC; for TMB-high tumors, any TPS% is allowed). For Cohort F8, any TPS (including 0%) is acceptable.

- * Adequate hematologic, coagulation, hepatic and renal function and ECOG score as defined per protocol.
Select Exclusion Criteria:
* Prior exposure to OX40 agonists. Exposure to anti-PD-1 and/or anti PD-L2 CPIs or an agent targeting other co-stimulatory T-cell receptor pathways.

- * Receipt of any investigational product or any approved anticancer drug(s) or biological product(s) within 4 weeks prior to the first dose of study drug with certain exceptions.

- * Hematologic malignancies (e.g., ALL, AML, MDS, CLL, CML, NHL, Hodgkin's lymphoma and multiple myeloma)

- * Prior or concurrent malignancies. Exception: Subjects with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessments of INBRX-106.

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

- * Active autoimmune disease or documented history of autoimmune disease that required systemic steroids or other immunosuppressive medications. Certain exceptions as defined in protocol apply.

- * Diagnosis of immunodeficiency or treatment with systemic immunosuppressive medications within 7 days prior to the first dose of study drug. Certain exceptions as 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 or pneumonitis requiring treatment with steroids or other immunosuppressive medications.

- * Clinically significant cardiac condition, including myocardial infarction, uncontrolled angina, viral myocarditis, cerebrovascular accident, or other acute uncontrolled heart disease < 3 months prior to enrollment on this trial; left ventricular ejection fraction (LVEF) < 50%; New York Heart Association (NYHA) Class III or IV congestive heart failure; or uncontrolled hypertension; or oxygen saturation <92% on room air. - * Active, hemodynamically significant pulmonary embolism within 12 weeks prior to enrollment 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 the first 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.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Clinical Lead

Role: Study Director

Affiliation: Inhibrx Biosciences, Inc

Overall Contact

Name: Study Director - Inhibrx Biosciences, Inc

Phone: 858-500-7833

Email: [email protected]

LOCATION