A Phase 1/2, Dose Escalation and Expansion Study of the Safety, Tolerability, and Anti-tumor Activity of BND-22 Administered Alone and in Combination With Pembrolizumab or With Cetuximab in Patients With Advanced Solid Tumors

Primary Outcome Measures  :

1. Part 1: Incidence of treatment-emergent adverse events (TEAEs) dose limiting toxicities (DLT) [ Time Frame: Cycle 1 (28 days) ]Incidence of TEAEs meeting protocol defined DLT criteria
   
2. Part 1: Incidence of treatment-emergent adverse events [ Time Frame: Through study completion, an average of 5 months ]
   
3. Part 2: Objective Response Rate (ORR) per RECIST v1.1 [ Time Frame: Through study completion, an average of 3 months ]Proportion of participants with a best overall response of complete response (CR) or partial response (PR) per RECIST v1.1
   

Secondary Outcome Measures  :

1. Part 1: Maximum observed plasma concentration [Cmax] [ Time Frame: Through study completion, an average of 2 months ]
   
2. Part 2: Maximum observed plasma concentration [Cmax] [ Time Frame: Through study completion, an average of 3 months ]
   
3. Part 1: Terminal elimination half-life [T1/2] [ Time Frame: Through study completion, an average of 2 months ]
   
4. Part 2: Terminal elimination half-life [T1/2] [ Time Frame: Through study completion, an average of 3 months ]
   
5. Part 1: Area under the plasma concentration-time curve [AUC] [ Time Frame: Through study completion, an average of 2 months ]
   
6. Part 2: Area under the plasma concentration-time curve [AUC] [ Time Frame: Through study completion, an average of 3 months ]
   
7. Part 1: Incidence of anti-drug antibodies (ADA) [ Time Frame: Through study completion, an average of 5 months ]
   
8. Part 2: Incidence of anti-drug antibodies (ADA) [ Time Frame: Through study completion, an average of 6 months ]
   
9. Part 2: Progression Free Survival [ Time Frame: Through study completion, an average of 3 months ]Time from the date of first dose of study drug to the date of first documented disease progression or death
   
10. Part 2: Duration of Response [ Time Frame: Through study completion, an average of 6 months ]Duration between first documentation of CR or PR to first documentation of disease progression or death
    
11. Part 2: Incidence of Serious Adverse Events and Adverse Events [ Time Frame: Through study completion, an average of 6 months ]
    

Inclusion Criteria:

• Patients with unresectable or metastatic disease who are refractory to or are not candidates for standard approved therapy
• Histologic confirmation of malignancy
• Measurable disease per RECIST v1.1
• Eastern Cooperative Oncology Group Performance Status (ECOG) of 0 or 1
• Participants must have adequate organ function as defined by lab tests
• Part 1: Following tumor types: Breast cancer, cervical cancer, colorectal cancer, adenocarcinoma or squamous cell carcinoma of the esophagus, gastric or gastroesophageal junction adenocarcinoma, squamous cell carcinoma of the head and neck, hepatobiliary cancers (hepatocellular carcinoma (HCC), gallbladder cancer, cholangiocarcinoma), non-small cell lung cancer, renal cell carcinoma, squamous cell carcinoma of the skin, or urothelial carcinoma
• Part 2: Following tumor types: Squamous cell carcinoma of the head and neck, Gastric or gastroesophageal junction adenocarcinoma, Non-small cell lung cancer

Exclusion Criteria:

• Active, known or suspected autoimmune disease
• Condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications
• Brain or leptomeningeal metastases
• Known history of positive test for HIV
• Non-HCC patients: acute or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV); HCC patients: untreated active HBV or dual infection with HBV/HCV
• Participants after solid organ or allogeneic hematopoietic stem cell transplant
• History of life-threatening toxicity related to prior immune therapy
• History of life-threatening toxicity related to prior cetuximab or other anti-EGFR antibodies (for Sub-Part 1C)
• Unstable or deteriorating cardiovascular disease within the previous 6 months
• Any major surgery within 4 weeks of study drug administration
• Prior/Concomitant Therapy:
• Cytotoxic/Non-cytotoxic anti-cancer agents, unless at least 4 weeks have elapsed from last dose
• Use of other investigational drugs within 28 days
• Prior treatment with macrophage or natural killer (NK) cells activating therapies
• Administration of a live attenuated vaccine within 28 days