Clinical Trial: NCT01803282 - My Cancer Genome

NCT01803282

Description:

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.

Related Conditions:

Adenocarcinoma of the Gastroesophageal Junction
Esophageal Carcinoma
Gastric Adenocarcinoma
Malignant Solid Tumor
Non-Small Cell Lung Carcinoma
Pancreatic Carcinoma

Recruiting Status:

Completed

Phase:

Phase 1

URL:

https://clinicaltrials.gov/show/NCT01803282

Trial Eligibility

Document

Title

Brief Title: 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

Clinical Trial IDs

ORG STUDY ID: GS-US-296-0101
NCT ID: NCT01803282

Conditions

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

Interventions

Drug	Synonyms	Arms
Andecaliximab	GS-5745	Part A: ADX 1800 mg
Gemcitabine		Part B: PAC, ADX 800 mg
Nab-paclitaxel		Part B: PAC, ADX 800 mg
Carboplatin		Part B: LAC, ADX 1200 mg
Pemetrexed		Part B: LAC, ADX 1200 mg
Leucovorin		Part B: EGC, ADX 800 mg
Oxaliplatin		Part B: EGC, ADX 800 mg
5-FU		Part B: EGC, ADX 800 mg
Bevacizumab		Part B: FL CRC, ADX 800 mg+BEV 10 mg/kg
Irinotecan		Part B: SL CRC, ADX 800 mg+BEV 10 mg/kg
Paclitaxel		Part B: BRCA, ADX 800 mg

Purpose

Trial Arms

Name	Type	Description	Interventions
Part A: ADX 200 mg	Experimental	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.	Andecaliximab
Part A: ADX 600 mg	Experimental	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.	Andecaliximab
Part A: ADX 1800 mg	Experimental	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	Andecaliximab
Part B: PAC, ADX 800 mg	Experimental	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.	Andecaliximab Gemcitabine Nab-paclitaxel
Part B: LAC, ADX 1200 mg	Experimental	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.	Andecaliximab Carboplatin Pemetrexed
Part B: LSC, ADX 1200 mg	Experimental	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.	Andecaliximab Carboplatin Paclitaxel
Part B: EGC, ADX 800 mg	Experimental	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.	Andecaliximab Leucovorin Oxaliplatin 5-FU
Part B: FL CRC, ADX 800 mg+BEV 5 mg/kg	Experimental	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.	Andecaliximab Leucovorin Oxaliplatin 5-FU Bevacizumab
Part B: FL CRC, ADX 800 mg+BEV 10 mg/kg	Experimental	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.	Andecaliximab Leucovorin Oxaliplatin 5-FU Bevacizumab
Part B: SL CRC, ADX 800 mg+BEV 5 mg/kg	Experimental	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.	Andecaliximab Leucovorin 5-FU Bevacizumab Irinotecan
Part B: SL CRC, ADX 800 mg+BEV 10 mg/kg	Experimental	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.	Andecaliximab Leucovorin 5-FU Bevacizumab Irinotecan
Part B: BRCA, ADX 800 mg	Experimental	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.	Andecaliximab Paclitaxel

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.

Maximum Eligible Age:	N/A
Minimum Eligible Age:	18 Years
Eligible Gender:	All
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	Percentage of Participants Experiencing Treatment-Emergent Adverse Events
Time Frame:	Part A: First dose date up to 32 weeks plus 30 days; Part B: First dose date up to 181 weeks plus 30 days
Safety Issue:
Description:	Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. Participants with any laboratory abnormality were reported.

Details

Phase:	Phase 1
Primary Purpose:	Interventional
Overall Status:	Completed
Lead Sponsor:	Gilead Sciences

Trial Keywords

Solid Tumor

Last Updated

June 2, 2020

Clinical Trials /

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