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

Gilead Sciences

Status and phase: Completed; Phase 1

Conditions: Breast Cancer; Esophagogastric Cancer; Non-small Cell Lung Cancer; Colorectal Cancer; Pancreatic Cancer

Treatments: Drug: 5-FU; Drug: Pemetrexed; Drug: Andecaliximab; Drug: Bevacizumab; Drug: Paclitaxel; Drug: Gemcitabine; Drug: Irinotecan; Drug: Oxaliplatin; Drug: Leucovorin; Drug: Nab-paclitaxel; Drug: Carboplatin

Study type: Interventional

Funder types: Industry

Identifiers

NCT01803282

GS-US-296-0101

Details and patient eligibility

About

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.

Enrollment: 236 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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236 participants in 12 patient groups

Part A: ADX 200 mg

Experimental group

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.

Treatment:

Drug: Andecaliximab

Part A: ADX 600 mg

Experimental group

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.

Treatment:

Drug: Andecaliximab

Part A: ADX 1800 mg

Experimental group

Description:

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

Treatment:

Drug: Andecaliximab

Part B: PAC, ADX 800 mg

Experimental group

Description:

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.

Treatment:

Drug: Gemcitabine

Drug: Nab-paclitaxel

Drug: Andecaliximab

Part B: LAC, ADX 1200 mg

Experimental group

Description:

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.

Treatment:

Drug: Andecaliximab

Drug: Pemetrexed

Drug: Carboplatin

Part B: LSC, ADX 1200 mg

Experimental group

Description:

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.

Treatment:

Drug: Paclitaxel

Drug: Andecaliximab

Drug: Carboplatin

Part B: EGC, ADX 800 mg

Experimental group

Description:

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.

Treatment:

Drug: 5-FU

Drug: Oxaliplatin

Drug: Leucovorin

Drug: Andecaliximab

Part B: FL CRC, ADX 800 mg+BEV 5 mg/kg

Experimental group

Description:

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.

Treatment:

Drug: 5-FU

Drug: Oxaliplatin

Drug: Leucovorin

Drug: Andecaliximab

Drug: Bevacizumab

Part B: FL CRC, ADX 800 mg+BEV 10 mg/kg

Experimental group

Description:

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.

Treatment:

Drug: 5-FU

Drug: Oxaliplatin

Drug: Leucovorin

Drug: Andecaliximab

Drug: Bevacizumab

Part B: SL CRC, ADX 800 mg+BEV 5 mg/kg

Experimental group

Description:

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.

Treatment:

Drug: 5-FU

Drug: Irinotecan

Drug: Leucovorin

Drug: Andecaliximab

Drug: Bevacizumab

Part B: SL CRC, ADX 800 mg+BEV 10 mg/kg

Experimental group

Description:

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.

Treatment:

Drug: 5-FU

Drug: Irinotecan

Drug: Leucovorin

Drug: Andecaliximab

Drug: Bevacizumab

Part B: BRCA, ADX 800 mg

Experimental group

Description:

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.

Treatment:

Drug: Paclitaxel

Drug: Andecaliximab