A Safety Study of SGN-CD47M in Patients With Solid Tumors

• ClinicalTrials.gov Identifier: NCT03957096
• Recruitment Status: Terminated
• First Posted: May 21, 2019
• Last Update Posted: September 17, 2020
• Sponsor: Seagen Inc.
• Information provided by (Responsible Party): Seagen Inc.

Study Description

Brief Summary:

This trial will study SGN-CD47M to find out whether it is an effective treatment for different types of solid tumors and what side effects (unwanted effects) may occur. The study will have two parts. Part A of the study will find out how much SGN-CD47M should be given for treatment and how often. Part B of the study will use the dose found in Part A and look at how safe and effective the treatment is.

Condition or disease	Intervention/treatment	Phase
Soft Tissue Sarcoma; Colorectal Cancer; Head and Neck Squamous Cell Carcinoma; Non-small Cell Lung Carcinoma; Breast Carcinoma; Ovarian Carcinoma; Exocrine Pancreatic Carcinoma; Gastric Carcinoma; Melanoma	Drug: SGN-CD47M	Phase 1

Detailed Description:

This is a dose-escalation study designed to evaluate the safety, tolerability, pharmacokinetics (PK), and antitumor activity of SGN-CD47M in adults with advanced solid tumors. The study will be conducted in 2 parts:

Part A - Dose escalation: Up to approximately 25 patients will be treated to evaluate the safety, tolerability, and PK of SGN-CD47M, and to identify the maximum tolerated dose (MTD) and/or optimal dose.

Part B - Dose expansion: Up to approximately 180 patients will be treated in expansion cohorts at the MTD or optimal dose to further characterize the safety, PK, and antitumor activity of SGN-CD47M.

In eligible patients, standard therapies must have failed, been intolerable, or been considered medically inappropriate by the investigator. If the MTD is not reached in Part A, safety, PK, pharmacodynamic, and biomarker analyses, as well as preliminary antitumor activity, will be used to determine the optimal dose. Patients in Part A may continue on treatment until confirmed progressive disease (PD) or unacceptable toxicity, whichever occurs first. The dose(s) to be examined in Part B will be at or below the MTD and/or the optimal dose determined in Part A.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 16 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1 Study of SGN-CD47M in Patients With Advanced Solid Tumors
• Actual Study Start Date: July 17, 2019
• Actual Primary Completion Date: September 14, 2020
• Actual Study Completion Date: September 14, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: SGN-CD47M	Drug: SGN-CD47M; SGN-CD47M administered intravenously

Outcome Measures

Primary Outcome Measures :

1. Number of patients with adverse events [ Time Frame: Up to approximately 24 months ]
2. Number of patients with laboratory abnormalities [ Time Frame: Up to approximately 24 months ]
3. Number of patients with dose-limiting toxicities (DLTs) [ Time Frame: 28 days ]

Secondary Outcome Measures :

1. Objective response rate (ORR) per RECIST v1.1 [ Time Frame: Up to approximately 2.5 years ]
   Defined as the proportion of patients with CR or PR
2. ORR per iRECIST [ Time Frame: Up to approximately 2.5 years ]
   Defined as the proportion of patients with iCR or iPR
3. Duration of objective response (DOR) per RECIST v1.1 [ Time Frame: Up to approximately 2.5 years ]
   Defined as the time from start of the first documentation of objective tumor response (CR or PR) to the first documentation of disease progression or to death due to any cause, whichever comes first
4. DOR per iRECIST [ Time Frame: Up to approximately 2.5 years ]
5. Duration of complete response (CR) per RECIST v1.1 [ Time Frame: Up to approximately 2.5 years ]
   Defined as the time from start of the first documentation of objective tumor response to the first documentation of confirmed tumor progression or to death due to any cause, whichever comes first for the subgroup of patients achieving a CR
6. Duration of CR per iRECIST [ Time Frame: Up to approximately 2.5 years ]
7. Progression-free survival (PFS) per RECIST v1.1 [ Time Frame: Up to approximately 2.5 years ]
   Defined as the time from start of study treatment to first documentation of disease progression or to death due to any cause, whichever comes first
8. PFS per iRECIST [ Time Frame: Up to approximately 2.5 years ]
9. Overall survival (OS) [ Time Frame: Up to approximately 4 years ]
   Defined as the time from the start of any study treatment to the date of death due to any cause
10. Area under the concentration-time curve (AUC) [ Time Frame: Up to approximately 24 months ]
11. Maximum concentration (Cmax) [ Time Frame: Up to approximately 24 months ]
12. Time to Cmax (Tmax) [ Time Frame: Up to approximately 24 months ]
13. Trough concentration (Ctrough) [ Time Frame: Up to approximately 24 months ]
14. Incidence of antidrug antibodies (ADA) [ Time Frame: Up to approximately 24 months ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Histologically or cytologically confirmed metastatic or unresectable solid malignancy within one of the following indications:

  1. Soft tissue sarcoma
  2. Colorectal carcinoma
  3. Non-small cell lung carcinoma
  4. Head and neck squamous cell carcinoma
  5. Breast carcinoma
  6. Ovarian carcinoma
  7. Exocrine pancreatic adenocarcinoma
  8. Gastric carcinoma
  9. Melanoma
• Relapsed, refractory, or progressive disease with no appropriate standard therapy available at the time of enrollment
• ECOG performance status of 0 or 1
• Measureable disease per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 at baseline
• Patients of childbearing potential may not be pregnant, must agree not to become pregnant until at 30 days after last dose of study drug, and must use 2 effective means of birth control.
• Patients who can father children must use 2 effective means of birth control and must agree not to donate sperm until at least 60 days after last dose of study drug.

Exclusion Criteria:

• History of another malignancy within 3 years prior to first dose of study drug (exceptions for malignancies with negligible risk of metastasis)
• Previous exposure to CD47 or SIRPα targeted therapy
• Chemotherapy, systemic radiotherapy, biologics, other anti-neoplastic or investigational agents, and/or other antitumor treatment with immunotherapy that is not completed 4 weeks prior to first dose of SGN-CD47M. Focal radiotherapy that is not completed 2 weeks prior to the first dose of SGN-CD47M
• Known active central nervous system metastases
• Positive for hepatitis B, active hepatitis C infections, positive for human immunodeficiency virus (HIV), or known active or latent tuberculosis
• History of sickle cell anemia, auto-immune hemolytic anemia, or idiopathic thrombocytopenic purpura
• Carcinomatous meningitis
• Red blood cell transfusion within 4 weeks prior to enrollment or platelet transfusion within 2 weeks prior to enrollment
• Any active Grade 3 or higher viral, bacterial, or fungal infection within 2 weeks prior to first dose
• History of a cerebral vascular event, unstable angina, myocardial infarction, or cardiac symptoms consistent with New York Heart Association Class III-IV within 6 months prior to first dose
• Condition requiring systemic treatment with corticosteroids or other immunosuppressive medications within 2 week prior to first dose
• Active autoimmune disease, autoimmune-related toxicity from prior immuno-oncology-based therapy
• Estimated life expectancy of less than 12 weeks

Contacts and Locations

Locations

United States, Ohio

Case Western Reserve University / University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States, 44106

United States, Oregon

Providence Portland Medical Center

Portland, Oregon, United States, 97213

United States, Tennessee

Tennessee Oncology-Nashvilee/Sarah Cannon Research Institute

Nashville, Tennessee, United States, 37203

United States, Texas

MD Anderson Cancer Center / University of Texas

Houston, Texas, United States, 77030-4095

NEXT Oncology

San Antonio, Texas, United States, 78229

Sponsors and Collaborators

Seagen Inc.

Investigators

• Study Director: Michael Schmitt, MD, PhD; Seagen Inc.

More Information

• Responsible Party: Seagen Inc.
• ClinicalTrials.gov Identifier: NCT03957096
• Other Study ID Numbers: SGN47M-001
• First Posted: May 21, 2019
• Last Update Posted: September 17, 2020
• Last Verified: September 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Seagen Inc.:

HNSCC; NSCLC

Additional relevant MeSH terms:

Carcinoma; Sarcoma; Breast Neoplasms; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Non-Small-Cell Lung; Pancreatic Neoplasms; Stomach Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Carcinoma, Squamous Cell; Neoplasms, Connective and Soft Tissue; Breast Diseases; Skin Diseases; Head and Neck Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Endocrine Gland Neoplasms; Endocrine System Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Pancreatic Diseases