Brief Title: A Study of SGN-B6A in Advanced Solid Tumors

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Number of participants with adverse events (AEs)

Primary Outcome 1 - Timeframe: 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

Primary Outcome 2 - Measure: Number of patients with laboratory abnormalities

Primary Outcome 2 - Timeframe: Through 30-37 days following last dose of SGN-B6A; up to 3 years

Primary Outcome 3 - Measure: Number of participants with dose-limiting toxicities (DLTs)

Primary Outcome 3 - Timeframe: Through 30-37 days following last dose of SGN-B6A; up to 3 years

CONDITION

• 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

ELIGIBILITY

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: Participants must be eligible for pembrolizumab monotherapy per local standard of care.

- * Part D only: Participants must not have received frontline systemic therapy for locally advanced or metastatic disease (prior definitively intended or adjuvant therapy is allowed with the exception of PD-[L]1).

- * 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 2 or greater per the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 5.0 (NCI CTCAE v5.0)

- * 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 Only: 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).

- * Part D Only: Has NSCLC with an actionable genomic alteration

- * 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

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Scott Knowles, MD, PhD

Role: Study Director

Affiliation: Seagen Inc.

Overall Contact

Name: Scott Knowles, MD, PhD

Phone: 866-333-7436

Email: clinicaltrials@seagen.com

LOCATION