A Study of SGN-B6A in Advanced Solid Tumors

This trial will look at a drug called SGN-B6A alone and with pembrolizumab, with or without chemotherapy, to find out whether it is safe for people who have solid tumors. It will study SGN-B6A to find out what its side effects are. A side effect is anything the drug does besides treating cancer. It will also study whether SGN-B6A works to treat solid tumors. The study will have four parts. Part A of the study will find out how much SGN-B6A should be given to participants. Part B will use the dose found in Part A to find out how safe SGN-B6A is and if it works to treat solid tumors. Part C of the study will find out how safe SGN-B6A is in combination with these other drugs. Part D will include people who have not received treatment. This part of the study will find out how safe SGN-B6A is in combination with these other drugs and if these combinations work to treat solid tumors. In Parts C and D, participants will receive SGN-B6A with either: Pembrolizumab or, Pembrolizumab and carboplatin, or Pembrolizumab and cisplatin.

Carcinoma, Non-Small Cell Lung, Squamous Cell Carcinoma of Head and Neck, HER2 Negative Breast Neoplasms, Esophageal Squamous Cell Carcinoma, Esophageal Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma, Ovarian Neoplasms, Cutaneous Squamous Cell Cancer, Exocrine Pancreatic Adenocarcinoma, Urinary Bladder Neoplasms, Uterine Cervical Neoplasms, Stomach Neoplasms

NSCLC, HNSCC, cSCC, ESCC, EAC, GEJ, HGSOC, Advanced HER2-Negative Breast Cancer, High Grade Serous Ovarian Cancer, Non-Small Cell Lung Cancer, Head and Neck Squamous Cell Cancer, Esophageal Cancer, Bladder Cancer, Cervical Cancer, Gastric Cancer, Seattle Genetics

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.

Through 30-37 days following last dose of SGN-B6A. For participants receiving pembrolizumab up to 90 days after last dose of pembrolizumab; up to 3 years

Confirmed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by investigator assessment

The proportion of participants with complete response (CR) or partial response (PR) which is subsequently confirmed as assessed according to RECIST v1.1.

The time from the first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of progressive disease (PD) or to death due to any cause

The time from the start of any study treatment to the first documentation of PD, or death due to any cause

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