Clinical trial NCT01803282: Study to Evaluate the Safety and Tolerability of Andecaliximab as Monotherapy and in Combination With Chemotherapy in Participants With Advanced Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pancreatic Cancer
Non-small Cell Lung Cancer
Esophagogastric Cancer
Colorectal Cancer
Breast Cancer
Keywords: Solid Tumor
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2013-03-04
Enrollment: 236
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Percentage of Participants Experiencing Treatment-Emergent Adverse Events
timeFrame: Part A: First dose date up to 32 weeks plus 30 days; Part B: First dose date up to 181 weeks plus 30 days
measure: Percentage of Participants Experiencing Laboratory Abnormalities
timeFrame: 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 outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Oncology
state: Alabama
city: Scottsdale
country: United States
facility: Pinnacle Oncology Hematology
state: Arizona
city: Bakersfield
country: United States
facility: Comprehensive Blood and Cancer Center
state: California
city: Encinitas
country: United States
facility: San Diego Pacific Oncology and Hematology Associates, Inc.
state: California
city: Los Angeles
country: United States
facility: University of Southern California (USC)
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: Santa Monica
country: United States
facility: UCLA Medical Center
state: California
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Fort Wayne
country: United States
facility: Parkview Research Center
state: Indiana
city: Goshen
country: United States
facility: Indiana University Health Goshen Center for Cancer Care
state: Indiana
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Cornell University
state: New York
city: Greenville
country: United States
facility: Greenville Health System, Institute for Translational Oncology Research
state: South Carolina
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Tacoma
country: United States
facility: Northwest Medical Specialties
state: Washington
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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
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. 15_suppl (May 20, 2018) 3578-3578
citation: 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
citation: 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
citation: 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
citation: 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
citation: 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
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 (ASCO) 52nd Annual Meeting; 2016 03 June- 07 June; Chicago, IL
citation: 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
citation: 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.