Brief Title: Phase 1, First-in-human, Dose-finding and Expansion Study to Evaluate XmAb®808 in Combination With Pembrolizumab in Advanced Solid Tumors

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Incidence of treatment-emergent adverse events (TEAEs)

Primary Outcome 1 - Timeframe: Up to 5 years

Primary Outcome 2 - Measure: Incidence of dose-limiting toxicities (DLTs)

Primary Outcome 2 - Timeframe: 49 days

CONDITION

• Head and Neck Squamous Cell Carcinoma
• Melanoma Excluding Uveal Melanoma
• Non-small Cell Lung Cancer
• Squamous or Non-squamous
• Urothelial Carcinoma
• Renal Cell Carcinoma
• Clear Cell
• Castration-resistant Prostate Cancer
• Ovarian Cancer
• Epithelial
• TNBC - Triple-Negative Breast Cancer
• Colorectal Cancer

ELIGIBILITY

Inclusion Criteria:
* Part A: Histologically confirmed advanced/metastatic castration-resistant prostate adenocarcinoma, epithelial ovarian cancer, head and neck squamous cell carcinoma, non-small cell lung cancer, urothelial carcinoma, melanoma, renal cell carcinoma, triple-negative breast cancer, or colorectal cancer that has progressed on standard therapies

- * Part B: Histologically confirmed advanced/metastatic castration-resistant prostate cancer that is PD1-naïve; head and neck squamous cell carcinoma that is PD1-naïve or has progressed on prior PD1 therapy; or melanoma that is PD1-naïve or has progressed on prior PD1 therapy

- * Measurable disease by RECIST 1.1; subjects with prostate cancer who have evaluable disease according to PCWG3 criteria may enroll

- * Life expectancy > 3 months

- * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

- * All subjects in Part A (dose escalation) must have adequate archival tumor sample. For subjects who do not have adequate archival tumor sample, a fresh tumor sample is mandatory.

- * All subjects in Part B (cohort expansion) must have a tumor lesion that can be biopsied and must agree to provide 2 fresh biopsies: one during screening and a second to be collected at the end of Cycle 1
Exclusion Criteria:
* Subjects currently receiving other anticancer therapies

- * Any prior treatment with an investigational agent targeting CD28

- * Treatment with systemic anticancer therapy (including immunotherapies) or radiation therapy within 4 weeks of the - start of study drug; a 1-week washout is allowed for palliative radiation; a 2-week washout is allowed for chemotherapy and small molecule (eg. kinase inhibitor) therapies

- * History of a life-threatening adverse event related to prior immunotherapy

- * Failure to recover from toxicity related to previous anticancer treatment

- * Known active central nervous system involvement by malignant disease. Subjects with - previously treated brain metastases may participate provided they are radiologically and clinically stable

- * Active known or suspected autoimmune disease (exceptions include subjects that have vitiligo; type 1 diabetes mellitus or residual hypothyroidism due to an autoimmune condition that is treatable with hormone replacement therapy only; psoriasis, atopic dermatitis, or another autoimmune skin condition that is managed without systemic therapy; or arthritis that is managed without systemic therapy beyond oral acetaminophen and nonsteroidal anti-inflammatory drugs)

- * Receipt of an organ allograft

- * Evidence of any serious bacterial, viral, parasitic, or systemic fungal infections within the 30 days prior to the first dose of study drug

- * Positive urine pregnancy test

- * Known hypersensitivity to pembrolizumab or to any ingredient in the formulation or component of the container

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Ben Thompson, MD PhD

Role: Study Director

Affiliation: Xencor, Inc.

Overall Contact

Name: Ben Thompson, MD PhD

Phone: (619) 517-7381, (858) 245-9419

Email: bthompson@xencor.com, asarot@xencor.com

LOCATION