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

NCT01803282 | Completed Phase 1 Results FDA Drug

• 1 other identifier: GS-US-296-0101
• Study Type: interventional
• Target: 236
• Locations: 1 country
• Sites: 18

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

Keywords

Solid Tumor

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants Experiencing Treatment-Emergent Adverse Events

  Part A: First dose date up to 32 weeks plus 30 days; Part B: First dose date up to 181 weeks plus 30 days

• Percentage of Participants Experiencing Laboratory Abnormalities

  Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. Participants with any laboratory abnormality were reported.

  Part A: First dose date up to 32 weeks plus 30 days; Part B: First dose date up to 181 weeks plus 30 days

Study Arms (12)

Part A: ADX 200 mg

EXPERIMENTAL

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.

Drug: Andecaliximab

Part A: ADX 600 mg

EXPERIMENTAL

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.

Drug: Andecaliximab

Part A: ADX 1800 mg

EXPERIMENTAL

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

Drug: Andecaliximab

Part B: PAC, ADX 800 mg

EXPERIMENTAL

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.

Drug: Andecaliximab; Drug: Gemcitabine; Drug: Nab-paclitaxel

Part B: LAC, ADX 1200 mg

EXPERIMENTAL

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.

Drug: Andecaliximab; Drug: Carboplatin; Drug: Pemetrexed

Part B: LSC, ADX 1200 mg

EXPERIMENTAL

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.

Drug: Andecaliximab; Drug: Carboplatin; Drug: Paclitaxel

Part B: EGC, ADX 800 mg

EXPERIMENTAL

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.

Drug: Andecaliximab; Drug: Leucovorin; Drug: Oxaliplatin; Drug: 5-FU

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

EXPERIMENTAL

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.

Drug: Andecaliximab; Drug: Leucovorin; Drug: Oxaliplatin; Drug: 5-FU; Drug: Bevacizumab

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

EXPERIMENTAL

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.

Drug: Andecaliximab; Drug: Leucovorin; Drug: Oxaliplatin; Drug: 5-FU; Drug: Bevacizumab

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

EXPERIMENTAL

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.

Drug: Andecaliximab; Drug: Leucovorin; Drug: 5-FU; Drug: Bevacizumab; Drug: Irinotecan

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

EXPERIMENTAL

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.

Drug: Andecaliximab; Drug: Leucovorin; Drug: 5-FU; Drug: Bevacizumab; Drug: Irinotecan

Part B: BRCA, ADX 800 mg

EXPERIMENTAL

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.

Drug: Andecaliximab; Drug: Paclitaxel

Interventions

Andecaliximab DRUG

Administered intravenous infusion

Also known as: GS-5745

Part A: ADX 1800 mg; Part A: ADX 200 mg; Part A: ADX 600 mg; Part B: BRCA, ADX 800 mg; Part B: EGC, ADX 800 mg; Part B: FL CRC, ADX 800 mg+BEV 10 mg/kg; Part B: FL CRC, ADX 800 mg+BEV 5 mg/kg; Part B: LAC, ADX 1200 mg; Part B: LSC, ADX 1200 mg; Part B: PAC, ADX 800 mg; Part B: SL CRC, ADX 800 mg+BEV 10 mg/kg; Part B: SL CRC, ADX 800 mg+BEV 5 mg/kg

Gemcitabine DRUG

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

Part B: PAC, ADX 800 mg

Nab-paclitaxel DRUG

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

Part B: PAC, ADX 800 mg

Carboplatin DRUG

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

Part B: LAC, ADX 1200 mg; Part B: LSC, ADX 1200 mg

Pemetrexed DRUG

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

Part B: LAC, ADX 1200 mg

Leucovorin DRUG

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

Part B: EGC, ADX 800 mg; Part B: FL CRC, ADX 800 mg+BEV 10 mg/kg; Part B: FL CRC, ADX 800 mg+BEV 5 mg/kg; Part B: SL CRC, ADX 800 mg+BEV 10 mg/kg; Part B: SL CRC, ADX 800 mg+BEV 5 mg/kg

Oxaliplatin DRUG

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

Part B: EGC, ADX 800 mg; Part B: FL CRC, ADX 800 mg+BEV 10 mg/kg; Part B: FL CRC, ADX 800 mg+BEV 5 mg/kg

5-FU DRUG

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

Part B: EGC, ADX 800 mg; Part B: FL CRC, ADX 800 mg+BEV 10 mg/kg; Part B: FL CRC, ADX 800 mg+BEV 5 mg/kg; Part B: SL CRC, ADX 800 mg+BEV 10 mg/kg; Part B: SL CRC, ADX 800 mg+BEV 5 mg/kg

Bevacizumab 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; Part B: FL CRC, ADX 800 mg+BEV 5 mg/kg; Part B: SL CRC, ADX 800 mg+BEV 10 mg/kg; Part B: SL CRC, ADX 800 mg+BEV 5 mg/kg

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

Paclitaxel 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: BRCA, ADX 800 mg; Part B: LSC, ADX 1200 mg

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (18)

Alabama Oncology

Birmingham, Alabama, 35243, United States

Location

Pinnacle Oncology Hematology

Scottsdale, Arizona, 85258, United States

Location

Comprehensive Blood and Cancer Center

Bakersfield, California, 93309, United States

Location

San Diego Pacific Oncology and Hematology Associates, Inc.

Encinitas, California, 92024, United States

Location

University of Southern California (USC)

Los Angeles, California, 90033, United States

Location

California Pacific Medical Center

San Francisco, California, 94115, United States

Location

UCLA Medical Center

Santa Monica, California, 90404, United States

Location

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

Location

Parkview Research Center

Fort Wayne, Indiana, 46845, United States

Location

Indiana University Health Goshen Center for Cancer Care

Goshen, Indiana, 46526, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Cornell University

New York, New York, 10021, United States

Location

Greenville Health System, Institute for Translational Oncology Research

Greenville, South Carolina, 29605, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Vanderbilt

Nashville, Tennessee, 37232, United States

Location

UT Southwestern

Dallas, Texas, 75390, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

Northwest Medical Specialties

Tacoma, Washington, 98405, United States

Location

Related Publications (11)

• 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.

  PMID: 29691300 RESULT

• 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

  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

  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

  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

  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

  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

  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

  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

  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

  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.

  PMID: 25961845 RESULT

MeSH Terms

Conditions

Pancreatic Neoplasms; Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms; Breast Neoplasms

Interventions

andecaliximab; Gemcitabine; 130-nm albumin-bound paclitaxel; Carboplatin; Pemetrexed; Leucovorin; Oxaliplatin; Fluorouracil; Bevacizumab; Irinotecan; Paclitaxel

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Camptothecin; Alkaloids; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: February 27, 2013
• First Posted: March 4, 2013
• Study Start: March 29, 2013
• Primary Completion: April 23, 2019
• Study Completion: April 23, 2019
• Last Updated: June 2, 2020
• Results First Posted: May 4, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (18)