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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01803282
Recruitment Status : Completed
First Posted : March 4, 2013
Results First Posted : May 4, 2020
Last Update Posted : June 2, 2020
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Study Description
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Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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.


Condition or disease Intervention/treatment Phase
Pancreatic Cancer Non-small Cell Lung Cancer Esophagogastric Cancer Colorectal Cancer Breast Cancer Drug: Andecaliximab Drug: Gemcitabine Drug: Nab-paclitaxel Drug: Carboplatin Drug: Pemetrexed Drug: Leucovorin Drug: Oxaliplatin Drug: 5-FU Drug: Bevacizumab Drug: Irinotecan Drug: Paclitaxel Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 236 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : March 29, 2013
Actual Primary Completion Date : April 23, 2019
Actual Study Completion Date : April 23, 2019

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: 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.
 Drug: Andecaliximab
Administered intravenous infusion
Other Name: GS-5745
Experimental: 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.
 Drug: Andecaliximab
Administered intravenous infusion
Other Name: GS-5745
Experimental: 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
 Drug: Andecaliximab
Administered intravenous infusion
Other Name: GS-5745
Experimental: 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.
 Drug: Andecaliximab
Administered intravenous infusion
Other Name: GS-5745

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

Drug: Nab-paclitaxel
Administered intravenously on Days 1, 8, and 15 of each 28-day treatment cycle
Experimental: 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.
 Drug: Andecaliximab
Administered intravenous infusion
Other Name: GS-5745

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

Drug: Pemetrexed
Administered intravenously on Day 1 of each 21-day treatment cycle
Experimental: 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.
 Drug: Andecaliximab
Administered intravenous infusion
Other Name: GS-5745

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

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)
Experimental: 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.
 Drug: Andecaliximab
Administered intravenous infusion
Other Name: GS-5745

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

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

Drug: 5-FU
Administered intravenously on Days 1 and 15 of each 28-day treatment cycle
Experimental: 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.
 Drug: Andecaliximab
Administered intravenous infusion
Other Name: GS-5745

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

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

Drug: 5-FU
Administered intravenously on Days 1 and 15 of each 28-day treatment cycle

Drug: Bevacizumab
Administered intravenously on Days 1 and 15 of each 28-day treatment cycle
Experimental: 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.
 Drug: Andecaliximab
Administered intravenous infusion
Other Name: GS-5745

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

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

Drug: 5-FU
Administered intravenously on Days 1 and 15 of each 28-day treatment cycle

Drug: Bevacizumab
Administered intravenously on Days 1 and 15 of each 28-day treatment cycle
Experimental: 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.
 Drug: Andecaliximab
Administered intravenous infusion
Other Name: GS-5745

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

Drug: 5-FU
Administered intravenously on Days 1 and 15 of each 28-day treatment cycle

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

Drug: Irinotecan
Administered intravenously on Days 1 and 15 of each 28-day treatment cycle
Experimental: 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.
 Drug: Andecaliximab
Administered intravenous infusion
Other Name: GS-5745

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

Drug: 5-FU
Administered intravenously on Days 1 and 15 of each 28-day treatment cycle

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

Drug: Irinotecan
Administered intravenously on Days 1 and 15 of each 28-day treatment cycle
Experimental: 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.
 Drug: Andecaliximab
Administered intravenous infusion
Other Name: GS-5745

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)


Outcome Measures
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Primary Outcome Measures :
  1. Percentage of Participants Experiencing Treatment-Emergent Adverse Events [ Time Frame: Part A: First dose date up to 32 weeks plus 30 days; Part B: First dose date up to 181 weeks plus 30 days ]
  2. Percentage of Participants Experiencing Laboratory Abnormalities [ Time Frame: Part A: First dose date up to 32 weeks plus 30 days; Part B: First dose date up to 181 weeks plus 30 days ]
    Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. Participants with any laboratory abnormality were reported.


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01803282


Locations
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Sponsors and Collaborators
Gilead Sciences
Investigators
Layout table for investigator information
Study Director: Gilead Study Director Gilead Sciences
  Study Documents (Full-Text)

Documents provided by Gilead Sciences:
Study Protocol  [PDF] August 1, 2016
Statistical Analysis Plan  [PDF] July 24, 2019

More Information
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Publications of Results:
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
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
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
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
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
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
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
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
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

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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01803282    
Other Study ID Numbers: GS-US-296-0101
First Posted: March 4, 2013    Key Record Dates
Results First Posted: May 4, 2020
Last Update Posted: June 2, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Gilead Sciences:
Solid Tumor
Additional relevant MeSH terms:
Layout table for MeSH terms
Leucovorin
Gemcitabine
Paclitaxel
Albumin-Bound Paclitaxel
Bevacizumab
Carboplatin
Oxaliplatin
Irinotecan
Pemetrexed
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
 Antineoplastic Agents, Immunological
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Topoisomerase I Inhibitors
Topoisomerase Inhibitors