CGX1321 in Subjects With Advanced Solid Tumors and CGX1321 With Pembrolizumab or Encorafenib + Cetuximab in Subjects With Advanced GI Tumors (Keynote 596)

NCT02675946 | Unknown Phase 1

• 2 other identifiers: CGX1321-101MK3475-596
• Study Type: interventional
• Target: 72
• Locations: 2 countries
• Sites: 26

Brief Summary

This is a multicenter, open-label study conducted in two phases: Phase 1 consisting of a CGX1321 Single Agent Dose Escalation Phase in solid tumors, CGX1321 Single Agent Dose Expansion Phase in GI tumors and Roll-over Cohort of CGX1321 and pembrolizumab in subjects who have progressed on single agent CGX1321 and Phase 1b consisting of CGX1321 in combination with pembrolizumab in colorectal tumors and CGX1321 in combination with encorafenib + cetuximab in BRAFV600E mutated colorectal tumors. Both phases are to evaluate safety, pharmacokinetics, and clinical activity.

Conditions

Solid Tumors; GI Cancer

Keywords

WNT inhibitor

Outcome Measures

Primary Outcomes (1)

• Number of participants with adverse events and/or abnormal laboratory values that are related to treatment

  safety

  55 months

Secondary Outcomes (5)

• CGX1321 area under the curve

  30 Days

• CGX1321 maximum or peak concentration

  30 Days

• CGX1321 minimum or trough concentration

  30 Days

• CGX1321 time to maximum concentration

  30 Days

• CGX1321 half-life

  30 Days

Study Arms (3)

Arm 1: CGX1321 Single Agent dose escalation and dose expansion

EXPERIMENTAL

Arm 1: Dose Escalation Phase: Ascending doses of CGX1321 once daily, orally, for 3 weeks (21 days) followed by a one-week (7-day) washout period in each 28-day cycle Dose Expansion Phase: CGX1321, at the MTD (identified in the Dose Escalation Phase), once daily, orally, for 3 weeks (21 days) followed by a one-week (7-day) washout period in each 28-day cycle.

Drug: CGX1321

Arm 2: CGX1321 in combination with pembrolizumab dose escalation, dose expansion and Roll-over,

EXPERIMENTAL

Arm 2: Roll-over Cohort: CGX1321 at a dose identified in Phase 1b, once daily, orally, for 2 weeks (14 days) followed by a one-week (7-day) washout period in combination with pembrolizumab administered IV once every three weeks (in each 21-day cycle). Arm 2: Phase 1b: Ascending doses of CGX1321, once daily, orally, for 2 weeks (14 days) followed by a one-week (7-day) washout period in combination with pembrolizumab administered IV once every three weeks (in each 21-day cycle).

Drug: CGX1321; Drug: Pembrolizumab

Arm 3: CGX1321 in combination with encorafenib + cetuximab, dose escalation and dose expansion

EXPERIMENTAL

Arm 3: Phase 1b: Ascending doses of CGX1321, once daily, orally for 3 weeks (21 days) followed by a one-week (7 day) washout period in combination with enocrafenib administered orally once daily and cetuximab administered IV once weekly

Drug: CGX1321; Drug: encorafenib; Drug: cetuximab

Interventions

CGX1321 DRUG

Arm 1: CGX1321 Single Agent dose escalation and dose expansion; Arm 2: CGX1321 in combination with pembrolizumab dose escalation, dose expansion and Roll-over,; Arm 3: CGX1321 in combination with encorafenib + cetuximab, dose escalation and dose expansion

Pembrolizumab DRUG

Also known as: Keytruda

Arm 2: CGX1321 in combination with pembrolizumab dose escalation, dose expansion and Roll-over,

encorafenib DRUG

Also known as: Braftovi

Arm 3: CGX1321 in combination with encorafenib + cetuximab, dose escalation and dose expansion

cetuximab DRUG

Also known as: Erbitux

Arm 3: CGX1321 in combination with encorafenib + cetuximab, dose escalation and dose expansion

Eligibility Criteria

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

You may qualify if:

• Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (Phase 1) or immune-related (ir)RECIST 1.1 (Phase 1b and Roll-over Cohort). Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
• Minimum estimated life expectancy of 3 months
• Age 18 years or older
• Must have adequate organ function, including the following:
• Absolute neutrophil count (ANC) ≥ 1.5 x109/L; platelet count ≥ 100 x 109/L; hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L
• International normalized ratio (INR) or prothrombin time (PT) and activated partial thromboplastin Time (aPTT) ≤ 1.5 times the upper limit of normal (ULN) unless subject is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
• Hepatic: total bilirubin ≤ 1.5 times ULN, aspartate transaminase (AST) and/or alanine aminotransferase (ALT) ≤ 2.5 times ULN (≤ 5 times ULN if liver metastases)
• Renal: serum creatinine ≤ 1.25 times the ULN or estimated creatinine clearance ≥ 60 mL/min (Cockcroft and Gault formula \[http://www.mdcalc.com/creatinine-clearance-cockcroft-gault-equation/\])
• Recovery (to baseline or to Grade 1 or less) from prior treatment-related toxicities
• Ability to swallow capsules
• Ability to comply with treatment, laboratory monitoring and required clinic visits
• Able to understand and willing to sign the informed consent form (ICF)
• In addition, the following criteria must be met based on the group to be enrolled into:
• For subjects in the Phase 1 Single Agent CGX1321 Dose Escalation phase:
• Pathologically-confirmed, locally advanced or metastatic solid tumors in subjects that have relapsed or are refractory to or are not considered medically suitable to receive standard of care treatment

You may not qualify if:

• All subjects must be excluded from participating in the study if subjects meet any of the following criteria:
• Prior exposure to a WNT inhibitor. Note: Not applicable for subjects entering Roll-over Cohort
• Received any of the following within the specified time frame prior to administration of study drug:
• Previous therapy for malignancy within 21 days, including any investigational agents, chemotherapy, immunotherapy, biological or hormonal therapy Note: Only applicable for subjects in single-agent dose escalation cohorts
• Major surgery within 4 weeks of first dose of study treatment
• Radiotherapy within 2 weeks of first dose of study treatment. Note for Phase 1b or Roll-over Cohorts: Subjects must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
• Significant GI or variceal bleeding or subdural hematoma within 3 months of first dose of study treatment
• Known active central nervous system metastases and/or carcinomatous meningitis Note: Subjects with previously treated brain metastases may participate provided they are radiographically stable (without evidence of progression by imaging (using the identical imaging modality for each assessment, either magnetic resonance imaging \[MRI\] or computed tomography \[CT\] scan) for at least four weeks prior to the first dose of study treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 14 days prior to the first dose of study treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug
• Currently receiving medications known to be inhibitors of CYP3A4/5. Subjects currently receiving medications of known inducers of CYP3A4/5 or substrates of CYP2C8/9 and CYP1A2 may be excluded unless determined by the Investigator to be in the best interest of the subject and are approved by the Sponsor
• Osteoporosis based on a T-score of \< -2.5 at the left or right total hip, left or right femoral neck or lumbar spine (L1 - L4) as determined by dual-energy x-ray absorptiometry (DXA) scan
• Subjects with bone metastases that:
• Have a prior history of a pathologic fracture
• Have a lytic lesion requiring an orthopedic intervention or
• Are not receiving a bisphosphonate (zoledronic acid or denosumab) as per institutional guidelines

Sponsors & Collaborators

• Curegenix Inc.: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (26)

Memorial Care

Long Beach, California, 90806, United States

NOT YET RECRUITING

St. Joseph's Santa Rosa

Santa Rosa, California, 95403, United States

NOT YET RECRUITING

Sarah Cannon Research Institute at HealthONE

Denver, Colorado, 80218, United States

COMPLETED

Hartford Health Care

Hartford, Connecticut, 06106, United States

NOT YET RECRUITING

Lombardi Comprehensive Cancer Center

Washington D.C., District of Columbia, 20007, United States

RECRUITING

Unknown Facility

Brooksville, Florida, 34613, United States

NOT YET RECRUITING

CSNF Cancer Specialists of North Florida (QCCA)

Jacksonville, Florida, 32256, United States

NOT YET RECRUITING

Ocala Oncology

Ocala, Florida, 34474, United States

NOT YET RECRUITING

University Cancer & Blood Center (QCCA)

Athens, Georgia, 30607, United States

NOT YET RECRUITING

Hawaii Cancer Center

Honolulu, Hawaii, 96813, United States

NOT YET RECRUITING

Edward H. Kaplan MD and Associates

Skokie, Illinois, 60076, United States

NOT YET RECRUITING

Goshen Health

Goshen, Indiana, 46526, United States

NOT YET RECRUITING

Community Health Network

Indianapolis, Indiana, 46250, United States

NOT YET RECRUITING

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21287, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Nebraska Cancer Specialists (QCCA)

Omaha, Nebraska, 68130, United States

NOT YET RECRUITING

Summit Medical Group

Florham Park, New Jersey, 07932, United States

NOT YET RECRUITING

Duke Cancer Center, Duke University Medical Center

Durham, North Carolina, 27710, United States

RECRUITING

Gettysburg Cancer Center

Gettysburg, Pennsylvania, 17325, United States

NOT YET RECRUITING

Sanford Health

Sioux Falls, South Dakota, 57104, United States

NOT YET RECRUITING

Baptist Cancer Center

Memphis, Tennessee, 38120, United States

NOT YET RECRUITING

START (South Texas Accelerated Research Therapeutics, LLC)

San Antonio, Texas, 78229, United States

COMPLETED

Northwest Medical Specialists (QCCA)

Tacoma, Washington, 98405, United States

NOT YET RECRUITING

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792, United States

RECRUITING

Taipei Medical University Hospital

Taipei, 11031, Taiwan

COMPLETED

MeSH Terms

Conditions

Gastrointestinal Neoplasms

Interventions

CGX1321; pembrolizumab; encorafenib; Cetuximab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Laurie Rosenstein

CONTACT

rosensteinl@us.curegenix.com

Study Design

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

Model Details: Enrollment to Single Agent Dose Expansion, Roll-over Cohort, Phase 1b CGX1321-101 in combination with pembrolizumab dose expansion and Phase 1b CGX1321 in combination with encorafenib + cetuximab dose escalation and dose expansion

Study Record Dates

• First Submitted: January 22, 2016
• First Posted: February 5, 2016
• Study Start: February 1, 2016
• Primary Completion: March 1, 2023
• Study Completion: March 1, 2023
• Last Updated: January 26, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1); US (25)