A Study of SGN-B6A in Advanced Solid Tumors

Inclusion Criteria:

Disease indication

Participants must have histologically or cytologically confirmed metastatic or unresectable solid malignancy within one of the tumor types listed below (dependent on study part).

Non-small cell lung cancer (NSCLC)
Head and neck squamous cell cancer (HNSCC)
Advanced HER2-negative breast cancer
Esophageal squamous cell carcinoma (ESCC)
Esophageal/Gastro-esophageal junction adenocarcinoma (EAC/GEJ)
Cutaneous squamous cell cancer (cSCC)
Exocrine pancreatic adenocarcinoma
Bladder cancer
Cervical cancer
Gastric cancer
High grade serous ovarian cancer (HGSOC)
Part A only: Participants must have disease that is relapsed or refractory or be intolerant to standard-of-care therapies and should have no appropriate standard-of-care therapeutic options.
Part B only: Participants must have disease that is relapsed or refractory or be intolerant to standard-of-care therapies. Participants must have received platinum-based therapy and a PD-1/PD-L1 inhibitor, if applicable and available.
Part C only: For pembrolizumab combination cohorts, participants must be eligible for pembrolizumab monotherapy per local standard of care. For pembrolizumab with cisplatin or carboplatin, participants must be eligible for both pembrolizumab and the platinum agent per local standard of care.
Part D only: Participants must be treatment naive for locally advanced or metastatic systemic therapy (prior definitively intended or adjuvant therapy is allowed with the exception of PD-[L]1 inhibitors).

Participants enrolled in the following study parts should have a tumor site accessible for biopsy and agree to biopsy as follows:

Disease-specific expansion cohorts (Part B and Part D): A baseline fresh tumor biopsy is required. An archival biopsy collected within 90 days may be used.
Biology expansion cohort: pretreatment biopsy and on-treatment (Cycle 1) biopsy
An Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
Measurable disease per the RECIST v1.1 at baseline

Exclusion Criteria

History of another malignancy within 3 years before first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy. Exceptions are malignancies with a negligible risk of metastasis or death.

Known active central nervous system metastases. 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,
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 first dose of study drug.
Carcinomatous meningitis
Previous receipt of an MMAE-containing agent or an agent targeting integrin beta-6
Pre-existing neuropathy Grade 1 or greater per the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 5.0 (NCI CTCAE v5.0) for Parts C and D cohorts with cisplatin or carboplatin; Grade 2 or greater per the NCI CTCAE v5.0 for all other cohorts

Any uncontrolled Grade 3 or higher (per NCI CTCAE v5.0) viral, bacterial, or fungal infection within 2 weeks prior to the first dose of SGN-B6A.

Routine antimicrobial prophylaxis is permitted
Grade ≥3 pulmonary disease unrelated to underlying malignancy. This includes clinically severe pulmonary function compromise resulting from clinically significant pulmonary illnesses
Part C and D: Prior therapy with a PD-1 inhibitor, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor and was discontinued from that treatment due to a Grade 3 or higher immune-mediated adverse event (IMAE).
History of noninfectious interstitial lung disease (ILD) or pneumonitis that required steroids, current ILD or pneumonitis, or suspected ILD or pneumonitis that cannot be ruled out by imaging at screening
Known diffusing capacity of the lung for carbon monoxide (DLCO; adjusted for hemoglobin) <50% predicted