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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01803282
• Other study ID #: GS-US-296-0101
• Status: Completed
• Phase: Phase 1
• Start date: March 29, 2013
• Est. completion date: April 23, 2019

Study information

• Verified date: May 2020
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 236
• Est. completion date: April 23, 2019
• Est. primary completion date: April 23, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Andecaliximab
Administered intravenous infusion
• Gemcitabine
Administered intravenously on Days 1, 8, and 15 of each 28-day treatment cycle
• Nab-paclitaxel
Administered intravenously on Days 1, 8, and 15 of each 28-day treatment cycle
• Carboplatin
Administered intravenously on Day 1 of each 21-day treatment cycle
• Pemetrexed
Administered intravenously on Day 1 of each 21-day treatment cycle
• Leucovorin
Administered intravenously on Days 1 and 15 of each 28-day treatment cycle
• Oxaliplatin
Administered intravenously on Days 1 and 15 of each 28-day treatment cycle
• 5-FU
Administered intravenously on Days 1 and 15 of each 28-day treatment cycle
• Bevacizumab
Administered intravenously on Days 1 and 15 of each 28-day treatment cycle
• Irinotecan
Administered intravenously on Days 1 and 15 of each 28-day treatment cycle
• 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)

Locations

Country	Name	City	State
United States	Comprehensive Blood and Cancer Center	Bakersfield	California
United States	Alabama Oncology	Birmingham	Alabama
United States	UT Southwestern	Dallas	Texas
United States	San Diego Pacific Oncology and Hematology Associates, Inc.	Encinitas	California
United States	Parkview Research Center	Fort Wayne	Indiana
United States	Indiana University Health Goshen Center for Cancer Care	Goshen	Indiana
United States	Greenville Health System, Institute for Translational Oncology Research	Greenville	South Carolina
United States	University of Southern California (USC)	Los Angeles	California
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Vanderbilt	Nashville	Tennessee
United States	Cornell University	New York	New York
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	University of Utah	Salt Lake City	Utah
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	Pinnacle Oncology Hematology	Scottsdale	Arizona
United States	Northwest Medical Specialties	Tacoma	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Country where clinical trial is conducted

United States, 

References & Publications (11)

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

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 3

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 2

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 Gastro

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 Ameri

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 (sup

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 Efficaci — View Citation

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 (ASC

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 G — View Citation

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. 1

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 f

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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