A Study of XmAb®22841 Monotherapy & in Combination w/ Pembrolizumab in Subjects w/ Selected Advanced Solid Tumors

Inclusion Criteria

• •PART A (Dose Escalation Cohorts)
• •1. All subjects' cancer must have progressed after treatment with all available therapies that are known to confer clinical benefit, or are intolerant to treatment, or refuse standard treatment.
• •2. All subjects must have adequate archival tumor, or give consent to a fresh tumor biopsy.
• •3. Subjects have an ECOG performance status of 0-1.
• •4. Subjects in monotherapy and combination therapy cohorts must have histologically or cytologically confirmed advanced or metastatic solid tumors, including the following:
• •1. Melanoma
• •2. Cervical carcinoma
• •3. Pancreatic carcinoma
• •4. Breast carcinoma that is estrogen receptor, progesterone receptor, and Her2 negative (TNBC)
• •5. Hepatocellular carcinoma
• •6. Urothelial carcinoma
• •7. Squamous cell carcinoma of the head and neck (HNSCC)
• •8. Nasopharyngeal carcinoma (NPC)
• •9. Renal cell carcinoma
• •10. Colorectal carcinoma or endometrial carcinoma
• •11. Small cell lung carcinoma or NSCLC
• •12. Gastric or gastroesophageal junction adenocarcinoma
• •13. Prostate adenocarcinoma
• •14. Epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer
• •15. Intrahepatic cholangiocarcinoma
• •5. Subjects in the combination cohorts in Part A with XmAb22841 and pembrolizumab may have an advanced solid tumor that either:
• •* has progressed after treatment with all available therapies that are known to confer clinical benefit, or is intolerant or has refused standard treatment (as for the XmAb22841 monotherapy cohorts), or
• •* is of a tumor type for which pembrolizumab is an approved indication and has not previously been treated with an agent targeting PD1 or PDL1.
• •PART B (Dose Expansion Cohorts)
• •XmAb22841 Single Agent Cohort
• •1\. Must have histologically or cytologically confirmed advanced or metastatic solid tumor that has progressed after treatment with all available therapies that are known to confer clinical benefit, or are intolerant to treatment, or refuse standard treatment. Eligible tumor types include the following:
• •1. Anti-PD1 refractory melanoma (or any uveal melanoma)
• •2. Anti-PD1 refractory NSCLC
• •3. Anti-PD1 refractory renal cell carcinoma (with clear cell component)
• •4. Anti-PD1 refractory urothelial carcinoma
• •5. Head and neck squamous cell carcinoma
• •6. Hepatocellular carcinoma
• •7. Gastric adenocarcinoma
• •8. Cervical carcinoma
• •9. Breast carcinoma that is estrogen receptor, progesterone receptor, and HER2 negative (TNBC)
• •10. Epithelial ovarian cancer
• •11. Nasopharyngeal carcinoma
• •12. Squamous cell anal carcinoma
• •13. Squamous cell penile carcinoma
• •14. Squamous cell vulvar carcinoma
• •XmAb22841 + Pembrolizumab Cohorts
• •1. Anti-PD-1 refractory melanoma (excluding uveal melanoma)
• •2. Anti-PD-1 naïve melanoma (excluding uveal melanoma)
• •3. Anti-PD-1 refractory NSCLC
• •4. Anti-PD1 naïve NSCLC
• •a. Must be PD-L1 high (TPS ≥ 50%), with no EGFR or ALK aberrations
• •5. Anti-PD1 naïve urothelial carcinoma
• •1. Must be PDL1 positive (CPS of ≥ 10), or ineligible for any platinum-containing chemotherapy regardless of PDL1 status; or
• •2. Had disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy