Safety and Tolerability Study in Solid Tumors

Study ID
GS-US-296-0101

Cancer Related
Yes

Healthy Volunteers
No

Study Sites

  • Clements University Hospital
  • UT Southwestern Ambulatory Services
  • Zale Lipshy University Hospital

Contact
Joyce Bolluyt
214/648-7007
joyce.bolluyt@utsouthwestern.edu

Principal Investigator
Saad Khan, M.D.

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

Brief Overview


This is an open-label, multicenter, sequential dose-escalation, and expansion study to
evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of 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 GS-5745 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
GS-5745 only. Part A will consist of between 12 to 48 participants.

Part B is a dose expansion to obtain additional safety and tolerability data for GS-5745 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 GS-5745 in combination with standard-of-care chemotherapy. Part
B will consist of between 115 to 265 participants.

Participant Eligibility


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

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