Study to Evaluate the Safety and Tolerability of Andecaliximab as Monotherapy and in Combination With Chemotherapy in Participants With Advanced Solid Tumors

NCT ID: NCT01803282

Last Updated: 2020-06-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 236 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-03-29
• Study Completion Date: 2019-04-23

Brief Summary

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.

Conditions

Pancreatic Cancer; Non-small Cell Lung Cancer; Esophagogastric Cancer; Colorectal Cancer; Breast Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part A: ADX 200 mg

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.

Group Type: EXPERIMENTAL

Andecaliximab

Intervention Type: DRUG

Administered intravenous infusion

Part A: ADX 600 mg

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.

Group Type: EXPERIMENTAL

Andecaliximab

Intervention Type: DRUG

Administered intravenous infusion

Part A: ADX 1800 mg

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

Group Type: EXPERIMENTAL

Andecaliximab

Intervention Type: DRUG

Administered intravenous infusion

Part B: PAC, ADX 800 mg

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.

Group Type: EXPERIMENTAL

Andecaliximab

Intervention Type: DRUG

Administered intravenous infusion

Gemcitabine

Intervention Type: DRUG

Administered intravenously on Days 1, 8, and 15 of each 28-day treatment cycle

Nab-paclitaxel

Intervention Type: DRUG

Administered intravenously on Days 1, 8, and 15 of each 28-day treatment cycle

Part B: LAC, ADX 1200 mg

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.

Group Type: EXPERIMENTAL

Andecaliximab

Intervention Type: DRUG

Administered intravenous infusion

Carboplatin

Intervention Type: DRUG

Administered intravenously on Day 1 of each 21-day treatment cycle

Pemetrexed

Intervention Type: DRUG

Administered intravenously on Day 1 of each 21-day treatment cycle

Part B: LSC, ADX 1200 mg

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.

Group Type: EXPERIMENTAL

Andecaliximab

Intervention Type: DRUG

Administered intravenous infusion

Carboplatin

Intervention Type: DRUG

Administered intravenously on Day 1 of each 21-day treatment cycle

Paclitaxel

Intervention Type: DRUG

Administered intravenously on Days 1, 8 and 15 of each 28-day treatment cycle (Breast cancer) or on Day 1 of each 21-day treatment cycle (NSCLC)

Part B: EGC, ADX 800 mg

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.

Group Type: EXPERIMENTAL

Andecaliximab

Intervention Type: DRUG

Administered intravenous infusion

Leucovorin

Intervention Type: DRUG

Administered intravenously on Days 1 and 15 of each 28-day treatment cycle

Oxaliplatin

Intervention Type: DRUG

Administered intravenously on Days 1 and 15 of each 28-day treatment cycle

5-FU

Intervention Type: DRUG

Administered intravenously on Days 1 and 15 of each 28-day treatment cycle

Part B: FL CRC, ADX 800 mg+BEV 5 mg/kg

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.

Group Type: EXPERIMENTAL

Andecaliximab

Intervention Type: DRUG

Administered intravenous infusion

Leucovorin

Intervention Type: DRUG

Administered intravenously on Days 1 and 15 of each 28-day treatment cycle

Oxaliplatin

Intervention Type: DRUG

Administered intravenously on Days 1 and 15 of each 28-day treatment cycle

5-FU

Intervention Type: DRUG

Administered intravenously on Days 1 and 15 of each 28-day treatment cycle

Bevacizumab

Intervention Type: DRUG

Administered intravenously on Days 1 and 15 of each 28-day treatment cycle

Part B: FL CRC, ADX 800 mg+BEV 10 mg/kg

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.

Group Type: EXPERIMENTAL

Andecaliximab

Intervention Type: DRUG

Administered intravenous infusion

Leucovorin

Intervention Type: DRUG

Administered intravenously on Days 1 and 15 of each 28-day treatment cycle

Oxaliplatin

Intervention Type: DRUG

Administered intravenously on Days 1 and 15 of each 28-day treatment cycle

5-FU

Intervention Type: DRUG

Administered intravenously on Days 1 and 15 of each 28-day treatment cycle

Bevacizumab

Intervention Type: DRUG

Administered intravenously on Days 1 and 15 of each 28-day treatment cycle

Part B: SL CRC, ADX 800 mg+BEV 5 mg/kg

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.

Group Type: EXPERIMENTAL

Andecaliximab

Intervention Type: DRUG

Administered intravenous infusion

Leucovorin

Intervention Type: DRUG

Administered intravenously on Days 1 and 15 of each 28-day treatment cycle

5-FU

Intervention Type: DRUG

Administered intravenously on Days 1 and 15 of each 28-day treatment cycle

Bevacizumab

Intervention Type: DRUG

Administered intravenously on Days 1 and 15 of each 28-day treatment cycle

Irinotecan

Intervention Type: DRUG

Administered intravenously on Days 1 and 15 of each 28-day treatment cycle

Part B: SL CRC, ADX 800 mg+BEV 10 mg/kg

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.

Group Type: EXPERIMENTAL

Andecaliximab

Intervention Type: DRUG

Administered intravenous infusion

Leucovorin

Intervention Type: DRUG

Administered intravenously on Days 1 and 15 of each 28-day treatment cycle

5-FU

Intervention Type: DRUG

Administered intravenously on Days 1 and 15 of each 28-day treatment cycle

Bevacizumab

Intervention Type: DRUG

Administered intravenously on Days 1 and 15 of each 28-day treatment cycle

Irinotecan

Intervention Type: DRUG

Administered intravenously on Days 1 and 15 of each 28-day treatment cycle

Part B: BRCA, ADX 800 mg

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.

Group Type: EXPERIMENTAL

Andecaliximab

Intervention Type: DRUG

Administered intravenous infusion

Paclitaxel

Intervention Type: DRUG

Administered intravenously on Days 1, 8 and 15 of each 28-day treatment cycle (Breast cancer) or on Day 1 of each 21-day treatment cycle (NSCLC)

Interventions

Andecaliximab

Administered intravenous infusion

Intervention Type: DRUG

Gemcitabine

Administered intravenously on Days 1, 8, and 15 of each 28-day treatment cycle

Intervention Type: DRUG

Nab-paclitaxel

Administered intravenously on Days 1, 8, and 15 of each 28-day treatment cycle

Intervention Type: DRUG

Carboplatin

Administered intravenously on Day 1 of each 21-day treatment cycle

Intervention Type: DRUG

Pemetrexed

Administered intravenously on Day 1 of each 21-day treatment cycle

Intervention Type: DRUG

Leucovorin

Administered intravenously on Days 1 and 15 of each 28-day treatment cycle

Intervention Type: DRUG

Oxaliplatin

Administered intravenously on Days 1 and 15 of each 28-day treatment cycle

Intervention Type: DRUG

5-FU

Administered intravenously on Days 1 and 15 of each 28-day treatment cycle

Intervention Type: DRUG

Bevacizumab

Administered intravenously on Days 1 and 15 of each 28-day treatment cycle

Intervention Type: DRUG

Irinotecan

Administered intravenously on Days 1 and 15 of each 28-day treatment cycle

Intervention Type: DRUG

Paclitaxel

Administered intravenously on Days 1, 8 and 15 of each 28-day treatment cycle (Breast cancer) or on Day 1 of each 21-day treatment cycle (NSCLC)

Intervention Type: DRUG

Other Intervention Names

GS-5745

Eligibility Criteria

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

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

Countries

United States

References

Shah MA, Starodub A, Sharma S, Berlin J, Patel M, Wainberg ZA, Chaves J, Gordon M, Windsor K, Brachmann CB, Huang X, Vosganian G, Maltzman JD, Smith V, Silverman JA, Lenz HJ, Bendell JC. Andecaliximab/GS-5745 Alone and Combined with mFOLFOX6 in Advanced Gastric and Gastroesophageal Junction Adenocarcinoma: Results from a Phase I Study. Clin Cancer Res. 2018 Aug 15;24(16):3829-3837. doi: 10.1158/1078-0432.CCR-17-2469. Epub 2018 Apr 24.

Reference Type: RESULT

PMID: 29691300 (View on PubMed)

Lenz H, Park H, Shah MA, Berlin JD, Bruetman D, Chaves J, et al. Results of a phase I study of andecaliximab in combination with mFOLFOX6 and bevacizumab in patients with previously untreated metastatic colorectal cancer. Annals of Oncology (2018) 29 (suppl_8): viii150-viii204

Reference Type: RESULT

Wainberg Z, Bendell J, Lenz H, Baron A, Berlin J, Bessudo A, et al. Results from a phase I study of andecaliximab in combination with FOLFIRI and bevacizumab in patients with second line metastatic colorectal cancer. Journal of Clinical Oncology 36, no. 15_suppl (May 20, 2018) 3578-3578

Reference Type: RESULT

Bendell J, Patel M, Brachmann C, Huang X, Maltzman J, Smith V, et al. Updated results of a phase 1 study combining the matrix metalloproteinase 9 inhibitor GS-5745 with gemcitabine and nab-paclitaxel in patients with advanced pancreatic cancer [Abstract 363] 2017 American Society of Clinical Oncology Gastrointestinal Cancers Symposium

Reference Type: RESULT

Brachmann C, Zhang Y, Zavodovskaya M, Hu J, Maltzman J, Smith V, et al. Evaluating collagen neoepitopes as pharmacodynamic biomarkers of GS-5745, an MMP9 inhibitor, in advanced gastric cancer [Abstract 58] 2017 American Society of Clinical Oncology Gastrointestinal Cancers Symposium

Reference Type: RESULT

Juric V, Mikels-Vigdal A, O'Sullivan C, Greenstein A, Stefanutti E, Barry-Hamilton V, et al. Inhibition of MMP9 improves anti-tumor immunity by changing the tumor microenvironment to promote T cell trafficking and activation. [Abstract 653/27]. 2017 American Association for Cancer Research Annual Meeting 110th Annual Meeting; 2017 01 April-05 April; Washington, DC

Reference Type: RESULT

Zavodovskaya M, Zhang Y, Xiao Y, Maltzman J, Smith V, Brachmann C, et al. Exploratory Serum Biomarker Analysis in Gastric Cancer Patients Treated with GS-5745, an MMP9 Inhibitor, in Combination with mFOLFOX6 [Abstract 4463/24]. 2017 American Association for Cancer Research Annual Meeting 110th Annual Meeting; 2017 01 April-05 April; Washington, DC

Reference Type: RESULT

Bendell J, Huang X, Smith V, Maltzman J, Starodub A. Results of a phase I study of GS-5745 in combination with gemcitabine and nab-paclitaxel in patients (pts) with advanced pancreatic cancer [abstract e15683] 2016. J Clin Oncol 34 supplemental

Reference Type: RESULT

Shah M, Starodub A, Wainberg Z, Smith V, Maltzman J, Bendell J. Results of a phase I study of GS-5745 in combination with mFOLFOX in patients with advanced unresectable gastric / GE junction tumors [Poster 4033]. American Society of Clinical Oncology (ASCO) 52nd Annual Meeting; 2016 03 June- 07 June; Chicago, IL

Reference Type: RESULT

Bendell J, Starodub A, Sharma S, Wainberg Z, Shah M, Thai D. Phase I Study of GS-5745 Alone and in Combination with Chemotherapy in Patients with Advanced Solid Tumors [Poster 4030]. American Society of Clinical Oncology (ASCO) 51st Annual Meeting; 2015 29 May-02 June; Chicago, IL

Reference Type: RESULT

Marshall DC, Lyman SK, McCauley S, Kovalenko M, Spangler R, Liu C, Lee M, O'Sullivan C, Barry-Hamilton V, Ghermazien H, Mikels-Vigdal A, Garcia CA, Jorgensen B, Velayo AC, Wang R, Adamkewicz JI, Smith V. Selective Allosteric Inhibition of MMP9 Is Efficacious in Preclinical Models of Ulcerative Colitis and Colorectal Cancer. PLoS One. 2015 May 11;10(5):e0127063. doi: 10.1371/journal.pone.0127063. eCollection 2015.

Reference Type: RESULT

PMID: 25961845 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

GS-US-296-0101

Identifier Type: -

Identifier Source: org_study_id