This is a first-in-human Phase 1a/1b, multicenter, open-label, dose-escalation and expansion study of TPST-1495 administered as a single agent and in combination with pembrolizumab to determine its maximum tolerated dose (MTD), safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary anti-tumor activity in subjects with advanced solid tumors. Subjects with all histologic types of solid tumors are eligible for the study. However, the preferred tumor types for enrollment are microsatellite-stable colorectal cancer (MSS CRC), adenocarcinoma of the lung, squamous cell carcinoma of the head and neck (SCCHN), bladder cancer, triple negative breast cancer (TNBC) and gastric cancer.
This is a first-in-human Phase 1a/1b, multicenter, open-label, dose-escalation and expansion
study of TPST-1495 administered as a single agent and in combination with pembrolizumab to
determine its MTD, safety, tolerability, pharmacokinetics (PD), pharmacodynamics (PK) and
preliminary anti-tumor activity in subjects with advanced solid tumors. Subjects with all
histologic types of solid tumors are eligible for the study. However, the preferred tumor
types for enrollment are microsatellite-stable colorectal cancer (MSS CRC), adenocarcinoma of
the lung, squamous cell carcinoma of the head and neck (SCCHN), bladder cancer, triple
negative breast cancer (TNBC) and gastric cancer. To be eligible, subjects must have no
remaining standard known to confer clinical benefit. This trial is composed of dose
escalation and dose expansion cohorts.
|Overal Status||Start Date||Phase||Study Type|
|Recruiting||May 6, 2020||Phase 1||Interventional|
Primary Outcome 1 - Measure: Determination of maximum tolerated dose based on dose limiting toxicities
Primary Outcome 1 - Time Frame: From start of treatment to treatment termination visit, up to 24 months
Subjects must meet all the following inclusion criteria to be eligible:
1. Subjects must have a histologically-confirmed malignancy that is metastatic or
unresectable for which there is no remaining standard therapy known to confer clinical
benefit. While all solid tumor types are eligible for the study, there is a preference
to enroll patients with MSS colorectal cancer, squamous cell carcinoma of the head and
neck, bladder cancer and triple negative breast cancer and gastric cancer. Prior anti
PD-1 or PDL-1 is permitted provided that the subject did not discontinue prior
therapies due to immune-related adverse events.
2. Subjects must have a tumor that is at least 1 cm in a single dimension and is
radiographically apparent on CT or MRI.
3. Eastern Cooperative Oncology Group performance status of 0 or 1 at enrollment
4. Life expectancy ≥ 12 weeks
5. Subjects must have received their last chemotherapy, biologic therapy or
investigational therapy at least 4 weeks prior to enrollment.
6. Adequate organ and marrow function (subjects must not have received transfusions or
growth factor support within 14 days prior to first dose of investigational product)
as defined below:
- Hemoglobin ≥ 10.0 g/dL
- Absolute neutrophil count ≥ 1,000 mm3
- Platelet count ≥ 100,000/mm3
- Bilirubin ≤ 1.5 × institutional upper limit of normal (ULN); for subjects with
documented/suspected Gilbert's disease, bilirubin should be ≤ 2 × ULN.
- Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 × ULN; for
subjects with liver metastases, AST or ALT ≤ 5 × ULN
- Creatinine ≤ 1.5×ULN OR calculated creatinine clearance (CrCl) ≥ 60 mL/min for
subjects with creatinine levels > 1.5× institutional ULN.
Subjects who meet any of the following exclusion criteria will not be eligible to receive
1. Concurrent enrollment in another clinical study, unless it is an observational (non
interventional) clinical study, a specimen-collection study or the follow-up period of
an interventional study. The use of an investigational device or agent must be stopped
at least 4 weeks prior to enrollment.
2. Chronic use (i.e., daily for 7 days or more) of nonsteroidal anti-inflammatory drugs
or COX-2 inhibitors within 2 weeks of enrollment.
3. Gastrointestinal ulcer or active colitis within 28 days of enrollment.
4. New York Heart Association Classification II, III or IV.
5. Baseline QTcF > 470 milliseconds
6. Receipt of live attenuated vaccines within 30 days prior to the first dose of
7. Active or prior documented autoimmune or inflammatory disorders including inflammatory
bowel disease (e.g., colitis or Crohn's disease), systemic lupus erythematosus,
Sarcoidosis syndrome, or Wegener syndrome (granulomatosis with polyangiitis, Graves'
disease, rheumatoid arthritis, hypophysitis, uveitis, etc.)
8. Active infection requiring therapy (including tuberculosis) or positive tests for
hepatitis B surface antigen (HBsAg) or hepatitis C antibody test and hepatitis C (HCV)
ribonucleic acid (RNA) test1. The HCV RNA test will be performed only for patients who
have positive HCV antibody test. Patients with a negative HBsAg test and a positive
total hepatitis B core antibody (HBcAb) test at screening are eligible for the study.
9. Uncontrolled intercurrent illness, including but not limited to, ongoing or active
infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
angina pectoris, cardiac arrhythmia, serious chronic gastrointestinal conditions
associated with diarrhea, or psychiatric illness/social situations including a history
of substance abuse that would limit compliance with study requirement, substantially
increase risk of incurring AEs or compromise the ability of the patient to give
written informed consent.
10. Administration of the following drugs is prohibited while taking TPST 1495: glyburide,
cefaclor, cefonicid, cefoxitin, cephradine, cidofovir, zidovudine, digoxin, docetaxel,
paclitaxel, pitavastatin, rosuvastatin, simvastatin or saquinavir
Minimum Age: 18 Years
Maximum Age: N/A
Healthy Volunteers: No
Name: Robert Stagg, PharmD
Role: Study Director
Affiliation: Tempest Therapeutics
Name: Tempest Clinical Trial Support
Grand Rapids, Michigan 49546
|Carolina BioOncology Institute
Huntersville, North Carolina 28078
Sophia Jean-Francois, BS
|South Texas Accelerated Research Therapeutics (START)
San Antonio, Texas 78229
Edwin F Blanco-Cepeda, BSN, RN