A Study of SGN-BB228 in Advanced Melanoma and Other Solid Tumors

Primary Outcome Measures

1. Number of participants with adverse events (AEs) [ Time Frame: Through 30 days after the last study treatment; approximately 7 months ]
   Any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment.
2. Number of participants with laboratory abnormalities [ Time Frame: Through 30 days after the last study treatment; approximately 7 months ]
3. Number of participants with dose limiting toxicities [ Time Frame: Up to 28 days ]

Secondary Outcome Measures

1. Number of participants with antidrug antibodies [ Time Frame: Through 30 days after the last study treatment; approximately 7 months ]
   To be summarized using descriptive statistics
2. Pharmacokinetic (PK) parameter – Area under the curve (AUC) [ Time Frame: Through 30 days after the last study treatment; approximately 7 months ]
   To be summarized using descriptive statistics
3. PK parameter – Maximum Concentration (Cmax) [ Time Frame: Through 30 days after the last study treatment; approximately 7 months ]
   To be summarized using descriptive statistics
4. PK parameter – Time to maximum concentration (Tmax) [ Time Frame: Through 30 days after the last study treatment; approximately 7 months ]
   To be summarized using descriptive statistics
5. PK parameter – Apparent terminal half-life (t1/2) [ Time Frame: Through 30 days after the last study treatment; approximately 7 months ]
   To be summarized using descriptive statistics
6. PK parameter – Trough concentration (Ctrough) [ Time Frame: Through 30 days after the last study treatment; approximately 7 months ]
   To be summarized using descriptive statistics
7. Objective response rate (ORR) [ Time Frame: Up to approximately 1 year ]
   The proportion of participants with a complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as assessed by the investigator
8. Duration of response (DOR) [ Time Frame: Up to approximately 1 year ]
   The time from start of the first documentation of objective tumor response (CR or PR) to the first documentation of progressive disease (PD) (based on radiographic assessments per RECIST v1.1) or death due to any cause
9. Progression-free survival (PFS) [ Time Frame: Up to approximately 1 year ]
   The time from the start of study treatment to the first documentation of PD (per RECIST v1.1 as assessed by the investigator) or death due to any cause
10. Overall survival (OS) [ Time Frame: Approximately 2 years ]
    The time from the start of study treatment to death due to any cause

Inclusion Criteria

• All Parts: Participants must have disease that is relapsed, refractory, or intolerant to standard of care. Participants must have histologically or cytologically confirmed metastatic malignancy.
• Participants must have one of the following tumor types:
  • Parts A and B: Participants must have unresectable cutaneous melanoma.
  • Part C: Participants must have one of the following tumor types:
    • Cutaneous Melanoma
    • Non-small Cell Lung Cancer (NSCLC)
    • Colorectal Cancer (CRC)
    • Pancreatic Cancer
    • Mesothelioma
• For participants with cutaneous melanoma
  • Must have been previously treated with an anti-programmed death-1 (anti-PD-1) or anti-programmed death ligand-1 (anti-PD-L1) agent given alone or with other therapies.
  • Participants with a targetable BRAF mutation must have been treated with, been intolerant of, or declined treatment with BRAF/MEK targeted therapy prior to study entry.
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
• Measurable disease per RECIST v1.1 at baseline

Exclusion Criteria

• History of another malignancy within 3 years before the first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy.
• Active central nervous system metastases or leptomeningeal disease. Participants with previously treated brain metastases may participate provided they are:
  • clinically stable for at least 4 weeks prior to study entry after brain metastasis treatment,
  • they have no new or enlarging brain metastases,
  • and are off of corticosteroids prescribed for symptoms associated with brain metastases for at least 7 days prior to the first dose of study drug.
• Prior therapies cannot include any drugs targeting CD228 or 4-1BB
• Immunotherapy, biologics, and/or other approved or investigational antitumor treatment that is not completed 4 weeks prior to first dose of study drug, or within 2 weeks prior to the first dose of study drug if the underlying disease has progressed on treatment