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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Pancreatic Cancer, Non-small Cell Lung Cancer, Esophagogastric Cancer, Colorectal Cancer, Breast Cancer

Intervention / Treatment
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* Drug: Andecaliximab
* Drug: Gemcitabine
* Drug: Nab-paclitaxel
* Drug: Carboplatin
* Drug: Pemetrexed
* Drug: Leucovorin
* Drug: Oxaliplatin
* Drug: 5-FU
* Drug: Bevacizumab
* Drug: Irinotecan
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: ADX 200 mg<br>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<br>* Administered intravenous infusion<br>* Other names: GS-5745;|
| Experimental: Part A: ADX 600 mg<br>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<br>* Administered intravenous infusion<br>* Other names: GS-5745;|
| Experimental: Part A: ADX 1800 mg<br>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<br>* Administered intravenous infusion<br>* Other names: GS-5745;|
| Experimental: Part B: PAC, ADX 800 mg<br>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<br>* Administered intravenous infusion<br>* Other names: GS-5745;Drug: Gemcitabine<br>* Administered intravenously on Days 1, 8, and 15 of each 28-day treatment cycle<br>Drug: Nab-paclitaxel<br>* Administered intravenously on Days 1, 8, and 15 of each 28-day treatment cycle<br>|
| Experimental: Part B: LAC, ADX 1200 mg<br>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<br>* Administered intravenous infusion<br>* Other names: GS-5745;Drug: Carboplatin<br>* Administered intravenously on Day 1 of each 21-day treatment cycle<br>Drug: Pemetrexed<br>* Administered intravenously on Day 1 of each 21-day treatment cycle<br>|
| Experimental: Part B: LSC, ADX 1200 mg<br>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<br>* Administered intravenous infusion<br>* Other names: GS-5745;Drug: Carboplatin<br>* Administered intravenously on Day 1 of each 21-day treatment cycle<br>Drug: Paclitaxel<br>* 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)<br>|
| Experimental: Part B: EGC, ADX 800 mg<br>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<br>* Administered intravenous infusion<br>* Other names: GS-5745;Drug: Leucovorin<br>* Administered intravenously on Days 1 and 15 of each 28-day treatment cycle<br>Drug: Oxaliplatin<br>* Administered intravenously on Days 1 and 15 of each 28-day treatment cycle<br>Drug: 5-FU<br>* Administered intravenously on Days 1 and 15 of each 28-day treatment cycle<br>|
| Experimental: Part B: FL CRC, ADX 800 mg+BEV 5 mg/kg<br>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<br>* Administered intravenous infusion<br>* Other names: GS-5745;Drug: Leucovorin<br>* Administered intravenously on Days 1 and 15 of each 28-day treatment cycle<br>Drug: Oxaliplatin<br>* Administered intravenously on Days 1 and 15 of each 28-day treatment cycle<br>Drug: 5-FU<br>* Administered intravenously on Days 1 and 15 of each 28-day treatment cycle<br>Drug: Bevacizumab<br>* Administered intravenously on Days 1 and 15 of each 28-day treatment cycle<br>|
| Experimental: Part B: FL CRC, ADX 800 mg+BEV 10 mg/kg<br>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<br>* Administered intravenous infusion<br>* Other names: GS-5745;Drug: Leucovorin<br>* Administered intravenously on Days 1 and 15 of each 28-day treatment cycle<br>Drug: Oxaliplatin<br>* Administered intravenously on Days 1 and 15 of each 28-day treatment cycle<br>Drug: 5-FU<br>* Administered intravenously on Days 1 and 15 of each 28-day treatment cycle<br>Drug: Bevacizumab<br>* Administered intravenously on Days 1 and 15 of each 28-day treatment cycle<br>|
| Experimental: Part B: SL CRC, ADX 800 mg+BEV 5 mg/kg<br>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<br>* Administered intravenous infusion<br>* Other names: GS-5745;Drug: Leucovorin<br>* Administered intravenously on Days 1 and 15 of each 28-day treatment cycle<br>Drug: 5-FU<br>* Administered intravenously on Days 1 and 15 of each 28-day treatment cycle<br>Drug: Bevacizumab<br>* Administered intravenously on Days 1 and 15 of each 28-day treatment cycle<br>Drug: Irinotecan<br>* Administered intravenously on Days 1 and 15 of each 28-day treatment cycle<br>|
| Experimental: Part B: SL CRC, ADX 800 mg+BEV 10 mg/kg<br>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<br>* Administered intravenous infusion<br>* Other names: GS-5745;Drug: Leucovorin<br>* Administered intravenously on Days 1 and 15 of each 28-day treatment cycle<br>Drug: 5-FU<br>* Administered intravenously on Days 1 and 15 of each 28-day treatment cycle<br>Drug: Bevacizumab<br>* Administered intravenously on Days 1 and 15 of each 28-day treatment cycle<br>Drug: Irinotecan<br>* Administered intravenously on Days 1 and 15 of each 28-day treatment cycle<br>|
| Experimental: Part B: BRCA, ADX 800 mg<br>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<br>* Administered intravenous infusion<br>* Other names: GS-5745;Drug: Paclitaxel<br>* 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)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Solid Tumor