Clinical trial NCT03957096: A Safety Study of SGN-CD47M in Patients With Solid Tumors
Official title: A Phase 1 Study of SGN-CD47M in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: 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
Keywords: HNSCC
NSCLC
Lead sponsor: Seagen Inc.
Sponsor class: INDUSTRY
First posted: 2019-05-21
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Number of patients with adverse events
timeFrame: Up to approximately 24 months
measure: Number of patients with laboratory abnormalities
timeFrame: Up to approximately 24 months
measure: Number of patients with dose-limiting toxicities (DLTs)
timeFrame: 28 days
Secondary outcomes:
measure: Objective response rate (ORR) per RECIST v1.1
timeFrame: Up to approximately 2.5 years
measure: ORR per iRECIST
timeFrame: Up to approximately 2.5 years
measure: Duration of objective response (DOR) per RECIST v1.1
timeFrame: Up to approximately 2.5 years
measure: DOR per iRECIST
timeFrame: Up to approximately 2.5 years
measure: Duration of complete response (CR) per RECIST v1.1
timeFrame: Up to approximately 2.5 years
measure: Duration of CR per iRECIST
timeFrame: Up to approximately 2.5 years
measure: Progression-free survival (PFS) per RECIST v1.1
timeFrame: Up to approximately 2.5 years
measure: PFS per iRECIST
timeFrame: Up to approximately 2.5 years
measure: Overall survival (OS)
timeFrame: Up to approximately 4 years
measure: Area under the concentration-time curve (AUC)
timeFrame: Up to approximately 24 months
measure: Maximum concentration (Cmax)
timeFrame: Up to approximately 24 months
measure: Time to Cmax (Tmax)
timeFrame: Up to approximately 24 months
measure: Trough concentration (Ctrough)
timeFrame: Up to approximately 24 months
measure: Incidence of antidrug antibodies (ADA)
timeFrame: Up to approximately 24 months
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Case Western Reserve University / University Hospitals Cleveland Medical Center
state: Ohio
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Nashville
country: United States
facility: Tennessee Oncology-Nashvilee/Sarah Cannon Research Institute
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center / University of Texas
state: Texas
city: San Antonio
country: United States
facility: NEXT Oncology
state: Texas
Study officials:
affiliation: Seagen Inc.
name: Michael Schmitt, MD, PhD
role: STUDY_DIRECTOR
References: