Safety and Tolerability Study in Solid Tumors

Study ID

Cancer Related

Healthy Volunteers

Study Sites

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

Joyce Bolluyt

Principal Investigator
Saad Khan

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 54 participants.

Part B is a dose expansion to obtain additional safety and tolerability data with GS-5745 in
participants with advanced pancreatic adenocarcinoma, lung adenocarcinoma, lung squamous
cell carcinoma, or esophagogastric adenocarcinoma. In Part B, participants will receive
GS-5745 in combination with standard-of-care chemotherapy. Part B will consist of between
70 to 145 participants.

Participant Eligibility

Inclusion Criteria:

1. Male or female > 18 years of age

2. 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

3. Part B Pancreatic Adenocarcinoma:

a. Presence of histologically confirmed inoperable locally advanced or metastatic
pancreatic adenocarcinoma

4. Part B NSCLC:

1. Stage IIIB with malignant pleural effusion/pleural seeding or stage IV
histologically confirmed NSCLC

2. Absence of known epidermal growth factor receptor (EGFR) mutation

3. Absence of known translocation or inversion events involving the ALK gene locus
(resulting in EML4-ALK fusion)

5. Part B Esophagogastric Adenocarcinoma:

1. Histologically confirmed inoperable advanced gastric adenocarcinoma (including
adenocarcinoma of the gastrooesophageal junction) or relapsed gastric

2. Human epidermal growth factor receptor 2 (HER2)-negative tumor (primary tumor or
metastatic lesion)

6. All acute toxic effects of any prior antitumor therapy resolved to Grade ≤ 1 before
the start of study drug dosing (with the exception of alopecia [Grade 1 or 2
permitted] and neurotoxicity [Grade 1 or 2 permitted])

7. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1

8. Life expectancy of > 3 months in the opinion of the Investigator

9. Adequate organ function defined as follows:

1. Hematologic: Platelets ≥ 100 x 10^9/L; Hemoglobin ≥ 9.0 g/dL; absolute
neutrophil count (ANC) ≥ 1.5 x 10^9/L

2. Hepatic: aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 x
ULN (if liver metastases are present, ≤ 5 x ULN); Total or conjugated bilirubin
≤ 1.5 x ULN

3. Renal: Serum Creatinine ≤ 1.5 x ULN

10. Coagulation: international normalized ratio (INR) ≤ 1.6 (unless receiving
anticoagulation therapy). Subjects on full-dose oral anticoagulation must be on a
stable dose (minimum duration 14 days). If receiving warfarin, the subject must have
an INR ≤ 3.0 and no active bleeding (ie, no bleeding within 14 days prior to first
dose of study drug). Subjects on low molecular weight heparin will be allowed.

11. For female subjects of childbearing potential, willingness to use a
protocol-recommended method of contraception from the screening visit throughout the
study treatment period and for 90 days following the last dose of study drugs. Note:
A female subject is considered to be of childbearing potential unless she has had a
hysterectomy, bilateral tubal ligation, or bilateral oophorectomy; has medically
documented ovarian failure (with serum estradiol and follicle-stimulating hormone
[FSH] levels within the institutional postmenopausal range and a negative serum or
urine Beta-HCG), or is menopausal (age > 55 years with amenorrhea for > 6 months).

12. For male subjects of childbearing potential having intercourse with females of
childbearing potential, willingness to use a protocol-recommended method of
contraception from the start of study drug, throughout the study treatment period,
and for 90 days following the last dose of study drugs, and to refrain from sperm
donation from the start of study drug, throughout the study treatment period, and for
90 days following the last dose of study drugs. Note: A male subject is considered
able to father a child unless he has had a bilateral vasectomy with documented
aspermia or a bilateral orchiectomy, or has ongoing testicular suppression with a
depot luteinizing hormone releasing hormone (LH RH) agonist (eg, goserelin acetate
[Zoladex®]), leuprolide acetate [Lupron®]), or triptorelin pamoate [Trelstar®]).

13. Willingness to comply with scheduled visits, drug administration plan, imaging
studies, laboratory tests, other study procedures, and study restrictions

14. Evidence of a signed informed consent form

Exclusion Criteria:

1. History or evidence of clinically significant disorder, condition, or disease that,
in the opinion of the Investigator and Medical Monitor would pose a risk to subject
safety or interfere with the study evaluations, procedures, or completion

2. Pregnant or lactating

3. Subject with known central nervous system (CNS) metastases, unless metastases are
treated and stable and the subject does not require systemic steroids

4. For Part B, small cell lung cancer

5. For Part B, diagnosis of pancreatic islet cell neoplasm

6. For Part B, subjects who have received prior cytotoxic chemotherapy to treat their
metastatic disease

7. Myocardial infarction, symptomatic congestive heart failure (New York Heart
Association Classification > Class II), unstable angina, or serious uncontrolled
cardiac arrhythmia within the last 6 months of study Day 1

8. History of major surgery within 28 days prior to enrollment

9. Serious systemic fungal, bacterial, viral, or other infection that is not controlled
or requires IV antibiotics

10. Anti-tumor therapy (chemotherapy, antibody therapy, molecular targeted therapy)
within 28 days or 5 half-lives, whichever is shorter, of study drug dosing (6 weeks
for nitrosoureas, mitomycin C, or molecular agents with t½ > 10 days); concurrent use
of hormone therapy for breast or prostate cancer is permitted

11. Clinically significant bleeding within 28 days of Day 1

12. Subjects known to be positive for human immunodeficiency virus (HIV), hepatitis C, or
hepatitis B