A Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GS-5745 as Monotherapy and in Combination With Chemotherapy in Subjects With Advanced Solid Tumors
| Registry | NCT01803282 |
|---|---|
| Status | Completed |
| Phase | Phase 1 |
| Study type | Interventional; non randomized, sequential, masking: none, treatment |
| Enrollment | 236 (Actual) |
| Sponsor | Gilead Sciences (Industry) |
| Conditions | Pancreatic Cancer, Non-small Cell Lung Cancer, Esophagogastric Cancer, Colorectal Cancer, Breast Cancer |
| Interventions | Andecaliximab, Gemcitabine, Nab-paclitaxel, Carboplatin, Pemetrexed, Leucovorin, Oxaliplatin, 5-FU, Bevacizumab, Irinotecan, Paclitaxel (Drug) |
| Dates | start 2013-03-29, primary completion 2019-04-23, completion 2019-04-23, first posted 2013-03-04, last updated 2020-06-02 |
| Locations | 18 sites in United States |
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The primary objective of the study is to determine the maximum tolerated dose of andecaliximab monotherapy and to evaluate the safety and tolerability of andecaliximab (formerly GS-5745) alone and in combination with chemotherapy.
The study consists of 2 parts (Parts A and B). Participants can only qualify for and participate in 1 part.
Part A is a sequential dose escalation to determine the maximum tolerated dose of andecaliximab in participants with advanced solid tumors that are refractory to or intolerant to standard therapy or for which no standard therapy exists. In Part A, participants will receive andecaliximab only.
Part B is a dose expansion to obtain additional safety and tolerability data for andecaliximab in participants with advanced pancreatic adenocarcinoma, lung adenocarcinoma, lung squamous cell carcinoma, esophagogastric adenocarcinoma, colorectal cancer, or breast cancer. In Part B, participants will receive andecaliximab in combination with standard-of-care chemotherapy.
| Arm | Type | Interventions | Description |
|---|---|---|---|
| Part A: ADX 200 mg | Experimental | Drug: Andecaliximab | Participants with advanced solid tumors who fail or are intolerant to standard therapy or for whom no standard therapy exists, will receive 200 mg ADX as monotherapy via IV infusion (approximately 30 minutes) every 2 weeks until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug. |
| Part A: ADX 600 mg | Experimental | Drug: Andecaliximab | Participants with advanced solid tumors who fail or are intolerant to standard therapy or for whom no standard therapy exists, will receive 600 mg ADX as monotherapy via IV infusion (approximately 30 minutes) every 2 weeks until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug. |
| Part A: ADX 1800 mg | Experimental | Drug: Andecaliximab | Participants with advanced solid tumors who fail or are intolerant to standard therapy or for whom no standard therapy exists, will receive 1800 mg ADX as monotherapy via IV infusion (approximately 30 minutes) every 2 weeks until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug |
| Part B: PAC, ADX 800 mg | Experimental | Drug: Andecaliximab; Drug: Gemcitabine; Drug: Nab-paclitaxel | Participants with PAC will receive ADX 800 mg every 2 weeks via IV infusion in addition to the 28-day cycle chemotherapy (gemcitabine and nab paclitaxel, on Days 1, 8, and 15) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug. |
| Part B: LAC, ADX 1200 mg | Experimental | Drug: Andecaliximab; Drug: Carboplatin; Drug: Pemetrexed | Participants with lung adenocarcinoma (LAC) will receive ADX 1200 mg every 3 weeks via IV infusion in addition to the 21-day cycle chemotherapy (carboplatin and pemetrexed, on Day 1) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug. |
| Part B: LSC, ADX 1200 mg | Experimental | Drug: Andecaliximab; Drug: Carboplatin; Drug: Paclitaxel | Participants with lung squamous cell carcinoma (LSC) will receive ADX 1200 mg every 3 weeks via IV infusion in addition to the 21-day cycle chemotherapy (carboplatin and paclitaxel, on Day 1) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug. |
| Part B: EGC, ADX 800 mg | Experimental | Drug: Andecaliximab; Drug: Leucovorin; Drug: Oxaliplatin; Drug: 5-FU | Participants with esophagogastric adenocarcinoma (EGC) will receive ADX 800 mg every 2 weeks via IV infusion in addition to the 28-day cycle chemotherapy (leucovorin+oxaliplatin+5-fluorouracil {5-FU} \[mFOLFOX6\], on Days 1 and 15) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug. |
| Part B: FL CRC, ADX 800 mg+BEV 5 mg/kg | Experimental | Drug: Andecaliximab; Drug: Leucovorin; Drug: Oxaliplatin; Drug: 5-FU; Drug: Bevacizumab | Participants with colorectal cancer (CRC) will receive first-line (FL) treatment with ADX 800 mg every 2 weeks via IV infusion in addition to the 28-day cycle chemotherapy (mFOLFOX6 and bevacizumab 5 mg/kg, on Days 1 and 15) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug. |
| Part B: FL CRC, ADX 800 mg+BEV 10 mg/kg | Experimental | Drug: Andecaliximab; Drug: Leucovorin; Drug: Oxaliplatin; Drug: 5-FU; Drug: Bevacizumab | Participants with CRC will receive FL treatment with ADX 800 mg every 2 weeks via IV infusion in addition to the 28-day cycle chemotherapy (mFOLFOX6 and bevacizumab 10 mg/kg, on Days 1 and 15) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug. |
| Part B: SL CRC, ADX 800 mg+BEV 5 mg/kg | Experimental | Drug: Andecaliximab; Drug: Leucovorin; Drug: 5-FU; Drug: Bevacizumab; Drug: Irinotecan | Participants with CRC will receive second-line (SL) treatment with ADX 800 mg every 2 weeks via IV infusion in addition to the 28-day cycle chemotherapy (leucovorin+irinotecan+5-FU \[FOLFIRI\] and bevacizumab 5 mg/kg, on Days 1 and 15) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug. |
| Part B: SL CRC, ADX 800 mg+BEV 10 mg/kg | Experimental | Drug: Andecaliximab; Drug: Leucovorin; Drug: 5-FU; Drug: Bevacizumab; Drug: Irinotecan | Participants with CRC will receive SL treatment with ADX 800 mg every 2 weeks via IV infusion in addition to the 28-day cycle chemotherapy (FOLFIRI and bevacizumab 10 mg/kg, on Days 1 and 15) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug. |
| Part B: BRCA, ADX 800 mg | Experimental | Drug: Andecaliximab; Drug: Paclitaxel | Participants with breast cancer (BRCA) will receive ADX 800 mg every 2 weeks via IV infusion in addition to the 28-day cycle chemotherapy (paclitaxel, on Days 1, 8, and 15) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug. |
Sex: All, ages: 18 Years to any
Key Inclusion Criteria: * Part A: histologically or cytologically confirmed advanced malignant solid tumor that is refractory to or intolerant of standard therapy or for which no standard therapy is available * Part B: Pancreatic Adenocarcinoma * Presence of histologically confirmed inoperable locally advanced or metastatic pancreatic adenocarcinoma * Part B: NSCLC * Stage IIIB with malignant pleural effusion/pleural seeding or stage IV histologically confirmed NSCLC * Absence of known epidermal growth factor receptor (EGFR) mutation * Absence of known translocation or inversion events involving the ALK gene locus (resulting in EML4-ALK fusion) * Part B: Esophagogastric Adenocarcinoma: * Histologically confirmed inoperable advanced gastric adenocarcinoma (including adenocarcinoma of the gastrooesophageal junction) or relapsed gastric adenocarcinoma * Human epidermal growth factor receptor 2 (HER2)-negative tumor (primary tumor or metastatic lesion) * Part B: First-Line Colorectal Cancer * Histologically confirmed inoperable advanced adenocarcinoma of the colon or rectum * Radiographically measureable disease * No prior cytotoxic chemotherapy to treat their metastatic disease * Part B: Second-Line Colorectal Cancer * Histologically confirmed inoperable advanced adenocarcinoma of the colon or rectum * Radiographically measureable disease * Received first-line combination therapy containing oxaliplatin and fluoropyrimidine with or without bevacizumab for metastatic disease with documented evidence of disease progression during or after treatment completion * Part B: Breast Cancer * Histologically or cytologically confirmed metastatic breast cancer * Radiographically measureable disease * Previous hormonal therapy for metastatic breast cancer or cytotoxic adjuvant chemotherapy is allowed * Treatment with weekly single-agent paclitaxel is appropriate in the opinion of the treating physician * HER-2 negative tumor (primary tumor or metastatic lesion) * Adequate organ function Key Exclusion Criteria: * Pregnant or lactating * Individuals with known central nervous system (CNS) metastases, unless metastases are treated and stable and the individual does not require systemic steroids * Myocardial infarction, symptomatic congestive heart failure, unstable angina, or serious uncontrolled cardiac arrhythmia within the last 6 months * Anti-tumor therapy within 28 days of study drug dosing; concurrent use of hormone therapy for breast or prostate cancer is permitted Note: Other protocol defined Inclusion/Exclusion criteria may apply.
| Facility | City | Country | Status |
|---|---|---|---|
| Alabama Oncology | Birmingham, Alabama | United States | |
| Pinnacle Oncology Hematology | Scottsdale, Arizona | United States | |
| Comprehensive Blood and Cancer Center | Bakersfield, California | United States | |
| San Diego Pacific Oncology and Hematology Associates, Inc. | Encinitas, California | United States | |
| University of Southern California (USC) | Los Angeles, California | United States | |
| California Pacific Medical Center | San Francisco, California | United States | |
| UCLA Medical Center | Santa Monica, California | United States | |
| Florida Cancer Specialists | Sarasota, Florida | United States | |
| Parkview Research Center | Fort Wayne, Indiana | United States | |
| Indiana University Health Goshen Center for Cancer Care | Goshen, Indiana | United States | |
| Washington University School of Medicine | St Louis, Missouri | United States | |
| Cornell University | New York, New York | United States | |
| Greenville Health System, Institute for Translational Oncology Research | Greenville, South Carolina | United States | |
| Sarah Cannon Research Institute | Nashville, Tennessee | United States | |
| Vanderbilt | Nashville, Tennessee | United States | |
| UT Southwestern | Dallas, Texas | United States | |
| University of Utah | Salt Lake City, Utah | United States | |
| Northwest Medical Specialties | Tacoma, Washington | United States |