Clinical trial · Interventional
Study to Evaluate the Safety and Tolerability of Andecaliximab as Monotherapy and in Combination With Chemotherapy in Participants With Advanced Solid Tumors
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
NCT01803282CI-TRIAL-00045366completedPhase 1Results postedClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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
Conditions (5)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Breast Cancer | Malignant Breast Neoplasm | CURATED_EXACT | 0.92 |
| Colorectal Cancer | Malignant Colorectal Neoplasm | CURATED_BROADER | 0.80 |
| Esophagogastric Cancer | — | UNRESOLVED | — |
| Non-small Cell Lung Cancer | Lung Non-Small Cell Carcinoma | ALIAS | 0.90 |
| Pancreatic Cancer | Malignant Pancreatic Neoplasm | CURATED_EXACT | 0.92 |
Interventions
Interventions (11)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| 5-FU | Drug | Fluorouracil | ALIAS |
| Andecaliximab | Drug | — | UNRESOLVED |
| Bevacizumab | Drug | Bevacizumab | ALIAS |
| Carboplatin | Drug | Carboplatin | ALIAS |
| Gemcitabine | Drug | Gemcitabine | ALIAS |
| Irinotecan | Drug | Irinotecan | ALIAS |
| Leucovorin | Drug | Leucovorin | ALIAS |
| Nab-paclitaxel | Drug | Nab-paclitaxel | ALIAS |
| Oxaliplatin |
Design
Arms and outcomes
Arms (12)
- type
- EXPERIMENTAL
- label
- Part A: ADX 200 mg
- description
- 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.
- interventionNames
- Drug: Andecaliximab
- type
- EXPERIMENTAL
- label
- Part A: ADX 600 mg
- description
- 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.
- interventionNames
- Drug: Andecaliximab
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
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.
References
Publications (11)
- RESULTShah 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
- RESULTLenz 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
- RESULTWainberg 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
- RESULTBendell 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
- RESULTBrachmann 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
- RESULTJuric 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
- RESULTZavodovskaya 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