Study To Evaluate The Safety And Tolerability Of Andecaliximab As Monotherapy And In Combination With Chemotherapy In Participants With Advanced Solid Tumors

Study Overview

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

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.

N/A

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

GS-US-296-0101

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2013-02-27	Results First Submitted 2020-04-20	Last Update Submitted that met QC Criteria 2020-05-20
First Submitted that Met QC Criteria 2013-02-28	Results First Submitted that Met QC Criteria 2020-04-20	Last Update Posted (ACTUAL) 2020-06-02
First Posted (ACTUAL) 2013-03-04	Results First Posted 2020-05-04	Last Verified 2020-05

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Sequential

Masking:
None

Arms and Interventions

Participant Group/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, unacc	DRUG: Andecaliximab Administered intravenous infusion
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, unacc	DRUG: Andecaliximab Administered intravenous infusion
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, unac	DRUG: Andecaliximab Administered intravenous infusion
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 oth	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,	DRUG: Andecaliximab Administered intravenous infusion 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	DRUG: Andecaliximab Administered intravenous infusion 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	DRUG: Andecaliximab Administered intravenous infusion 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, una	DRUG: Andecaliximab Administered intravenous infusion 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 o	DRUG: Andecaliximab Administered intravenous infusion 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 progres	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	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	DRUG: Andecaliximab Administered intravenous infusion 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)

Primary Outcome Measures	Measure Description	Time Frame
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

Secondary Outcome Measures	Measure Description	Time Frame

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

STUDY_DIRECTOR: Gilead Study Director, Gilead Sciences

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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.
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
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.

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