Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Clinical Activity of Defactinib in Combination With Avelumab in Epithelial Ovarian Cancer

NCT02943317 | Terminated Phase 1

• 1 other identifier: VS-6063-107
• Study Type: interventional
• Target: 98
• Locations: 1 country
• Sites: 5

Brief Summary

This is a Phase 1/1b, open-label, multicenter, dose-escalation and dose expansion trial to evaluate the safety, efficacy, PK and PD of defactinib (VS-6063) in combination with avelumab in epithelial ovarian cancer.

Conditions

Epithelial Ovarian Cancer

Outcome Measures

Primary Outcomes (3)

• Number of Participants taking defactinib in combination with avelumab with Adverse Events as a Measure of Safety and Tolerability

  Up to 90 days after last dose

• maximum tolerated dose (MTD) of defactinib in combination with avelumab (Part A)

  From start of treatment to end of Cycle 1 (28 days)

• best overall response according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (Part B)

  From start of treatment, assessed up to 52 weeks

Secondary Outcomes (7)

• time to treatment response disease control

  12, 24, 36, and 52 weeks

• best overall response according to immune-related response evaluation criteria in solid tumors (irRECIST)

  From start of treatment, assessed up to 52 weeks

• immune related progression-free survival (irPFS) time according to irRECIST and RECIST v1.1

  From start of treatment until first documented progression or death, whichever comes first, assessed up to 52 weeks

• progression-free survival (PFS) time according to irRECIST and RECIST v1.1

  From start of treatment until first documented progression or death, whichever comes first, assessed up to 52 weeks

• overall Survival (OS)

  From start of treatment until death, assessed up to 52 weeks

Study Arms (2)

Part A: VS-6063

EXPERIMENTAL

Part A - Oral VS-6063 (defactinib) twice-daily (BID) continuously starting on Day 1 of Cycle 1.

Drug: Part A - VS-6063

Part A: Avelumab

EXPERIMENTAL

Part A - avelumab IV treatment in 28-day cycles (10 mg/kg over approximately 1 hour on Days 1 and 15).

Drug: Part A - Avelumab

Interventions

Part A - VS-6063 DRUG

Part A - Oral VS-6063 (defactinib) twice-daily (BID) continuously starting on Day 1 of Cycle 1.

Also known as: Defactinib

Part A: VS-6063

Part A - Avelumab DRUG

Part A - avelumab IV treatment in 28-day cycles (10 mg/kg over approximately 1 hour on Days 1 and 15).

Part A: Avelumab

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to provide signed and dated informed consent before initiation of any study procedures.
• Willing and able to participate in the trial and comply with all trial requirements.
• Female subject aged ≥ 18 years.
• Histologically or cytologically-confirmed recurrent or resistant (progression within 6 months following the last administered platinum based therapy or progression after subsequent therapy in previously relapsed subjects), stage III-IV epithelial ovarian, fallopian tube or peritoneal cancer subjects (according to American Joint Committee on Cancer/Union for International Cancer Control TNM and International Federation of Gynecology and Obstetrics Staging System, 7th edition) whose disease has progressed following adjuvant therapy or therapy for metastatic disease.
• Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST 1.1.
• Confirmed availability of archived FFPE tumor tissue block, or a minimum of 15 slides. If archived FFPE tissue is not available, then fresh tumor sample may be obtained in accordance with local institutional practice for tumor biopsies.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1, measured within 72 hours before the start of treatment.
• Predicted life expectancy of ≥ 3 months.
• Adequate renal function with normal serum creatinine, or if creatinine above or below institutional normal range, a calculated glomerular filtration rate of ≥ 50 mL/min/1.73m2 (e.g., as calculated by the Cockcroft Gault formula) using actual body weight; if subject has body mass index \> 30 kg/m2, lean body weight must be used.
• Adequate hepatic function (total bilirubin ≤ 1.5 × upper limit of normal \[ULN\] for the institution; aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 × ULN.
• Adequate bone marrow function (hemoglobin \[Hb\] ≥ 9.0 g/dL \[subjects may be transfused to Hb ≥ 9.0 g/dL\]; platelets ≥ 100 × 109cells/L; absolute neutrophil count \[ANC\] ≥ 1.5 × 109 cells/L without the use of hematopoietic growth factors).
• Corrected QT interval (QTc) \< 470 msec (as calculated by the Fridericia correction formula \[QTcF\]).
• Negative pregnancy test within 72 hours prior to the first dose of protocol therapy for women of childbearing potential. Must be willing to use effective contraception for 30 days before the first study drug administration, for the duration of trial participation and at least for 60 days after stopping trial participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this trial, the treating physician must be informed immediately.

You may not qualify if:

• Concurrent anticancer treatment, major surgery or use of any investigational drug within 28 days or 5 half-lives, whichever is shorter, before the start of trial treatment; palliative radiation therapy is allowed if \> 21 days before planned first dose of study drugs and any toxicity is ≤ Grade 1.
• Concurrent systemic therapy with immunosuppressive agents; use of hormonal agents within 7 days before the start of trial treatment. Note: subjects receiving bisphosphonate or denosumab are eligible provided treatment was initiated at least 14 days before the first dose of avelumab. Subjects receiving immunosuppressive agents (such as corticosteroids) for any reason should be tapered off these drugs before initiation of the study treatment (with the exception of subjects with adrenal insufficiency, who may continue corticosteroids at physiologic replacement dose, equivalent to ≤ 10 mg prednisone daily). Steroids with no or minimal systemic effect (topical, inhalation) are allowed.
• Prior treatment with a drug of the focal adhesion kinase (FAK) inhibitor class.
• Prior therapy with specific antibody/drug targeting immune or coregulatory or costimulatory proteins (such as checkpoints e.g., PD-1 or PD L1, 4-1BB, OX40 or CTLA-4 antibodies).
• Receipt of any organ transplantation including autologous or allogeneic stem-cell transplantation.
• Uncontrolled brain metastases (Stable brain metastases either treated or being treated with a stable dose of anticonvulsants, with no dose change within 28 days before enrollment, will be allowed.).
• Women who are pregnant or breastfeeding.
• Any evidence of serious active infections; any infections being treated must complete antibiotic therapy at least 7 days before planned first dose.
• Active or history of any autoimmune disease (subjects with diabetes type 1, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible).
• Current acute or chronic colitis, inflammatory bowel disease, pneumonitis or pulmonary fibrosis.
• Known severe hypersensitivity reactions to monoclonal antibodies; any history of anaphylaxis or uncontrolled asthma.
• Uncontrolled or severe cardiovascular disease, including myocardial infarct or unstable angina within 6 months before study treatment, New York Heart Association Class II or greater congestive heart failure, serious arrhythmias requiring medication for treatment, clinically significant pericardial disease or cardiac amyloidosis.
• Known history of stroke or cerebrovascular accident within 6 months before enrollment.
• Known infection with human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS) (testing not required).
• Active hepatitis B or C (testing required).

Sponsors & Collaborators

• Verastem, Inc.: lead

Study Sites (5)

Florida Cancer Specialists & Research Institute (FCS)

Sarasota, Florida, 34232, United States

Location

Dana Farber Cancer Instiyute

Boston, Massachusetts, 02215, United States

Location

Stephenson Cancer Center (University of Oklahoma)

Oklahoma City, Oklahoma, 73104, United States

Location

Sarah Cannon Research Institute at Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Mary Crowley Cancer Research Centers

Dallas, Texas, 75251, United States

Location

MeSH Terms

Conditions

Carcinoma, Ovarian Epithelial

Interventions

defactinib

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Ovarian Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Study Officials

• Hagop Youssoufian, MD

  Verastem, Inc.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 17, 2016
• First Posted: October 24, 2016
• Study Start: October 1, 2016
• Primary Completion: August 28, 2018
• Study Completion: December 28, 2018
• Last Updated: April 30, 2019

Record last verified: 2018-07

Locations

US (5)