Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma, Non-Small-Cell Lung

Carcinoma

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Lung Neoplasms

Adenocarcinoma

Carcinoma, Transitional Cell

Endometrial Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Head and Neck Neoplasms

Transitional Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Reproductive Control Agents

Pembrolizumab

Dinoprostone

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Subjects will receive escalating doses of TPST-1495 administered orally twice daily until maximum tolerated dose is reached or until disease progression

Subjects will receive alternative TPST-1495 administration schedules until RP2D for the selected schedule is determined or until disease progression.

Subjects will receive selected dose regimen from dose and schedule optimization stage until disease progression

Subjects will receive alternative TPST-1495 administration schedules in combination with pembrolizumab until RP2D for the selected schedule is determined or until disease progression.

TPST-1495 administered orally twice daily

TPST-1495 twice daily

TPST-1495 administered orally once daily or on intermittent schedule

TPST-1495 once daily or on intermittent schedule

Pembrolizumab dosed per label recommendations

Samuel Whiting, MD PhD

This is a first-in-human Phase 1a/1b, multicenter, open-label, dose-escalation, dose and schedule optimization, and expansion study of TPST-1495 as a single agent and in combination with pembrolizumab to determine its maximum tolerated dose (MTD) and or recommended Phase 2 dose (RP2D), 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 escalation and dose-finding portions of the study. However, the preferred tumor types for enrollment are colorectal cancer (CRC), non-small cell lung cancer (NSCLC), squamous cell carcinoma of the head and neck (SCCHN), urothelial cancer, endometrial cancer, and gastroesophageal junction (GEJ) or gastric adenocarcinoma. Enrollment in the expansion cohorts is limited to the following tumor types: endometrial, SCCHN, CRC, and a basket cohort in subjects selected for an activating mutation in PIK3Ca.

This is a first-in-human Phase 1a/1b, multicenter, open-label, dose-escalation, dose and schedule optimization, and expansion study of TPST-1495 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 colorectal cancer (CRC), non-small cell lung cancer (NSCLC), squamous cell carcinoma of the head and neck (SCCHN), urothelial cancer, endometrial cancer, and gastroesophageal junction (GEJ) or gastric adenocarcinoma. Tumor prostaglandin production and downstream signaling in both tumor cells and other cell types, including immune suppressive cell population in the tumor microenvironment, is thought to be a principal driver of progression in each of these selected malignancies. To be eligible, subjects must have no remaining standard therapy known to confer clinical benefit.

The study is composed of 3 stages. The Dose-Escalation stage will determine the MTD of single-agent TPST-1495 administered twice a day (BID). The Schedule and Dose Optimization stage will evaluate alternative TPST-1495 single-agent administration schedules and determine an RP2D for the selected schedule. This arm will also evaluate TPST-1495 in combination with pembrolizumab. The Expansion stage will evaluate the activity of TPST-1495 as a single agent and in combination with pembrolizumab at the selected schedule and dose in disease-specific cohorts and in a basket cohort in subjects selected for an activating mutation in PIK3Ca.

open-label dose escalation, schedule and dose optimization, and dose expansion

Phase 1a/1b Study of TPST-1495 as a Single Agent and in Combination With Pembrolizumab in Subjects With Solid Tumors

Phase 1a/1b Open Label Dose-escalation and Expansion Study of TPST-1495 as a Single Agent and in Combination With Pembrolizumab in Subjects With Solid Tumors

Determination of maximum tolerated dose and/or recommended Phase 2 dose (RP2D) and optimum dose schedule for TPST-1495 as a single agent and in combination with pembrolizumab based on dose limiting toxicities

Incidence of treatment-emergent adverse events and serious adverse events for TPST-1495

Maximum serum concentration (Cmax) of TPST-1495

Area under the serum concentration-time curve (AUC) of TPST-1495

Terminal elimination half-life (t 1/2) of TPST-1495

Preliminary efficacy of TPST-1495 as a single agent and in combination with pembrolizumab as assessed by overall response rate (ORR) using RECIST version 1.1

Preliminary efficacy of TPST-1495 as a single agent and in combination with pembrolizumab as assessed by progression free survival (PFS)

Preliminary efficacy of TPST-1495 as a single agent and in combination with pembrolizumab as assessed by duration of response (DoR)

Tempest Therapeutics

Digestive System Diseases

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

14-day cycles of combined AGEN2034 3 mg/Kg iv on D1 of each cycle, and oral CR6086 30 mg twice a day for 14 days

14-day cycles of combined AGEN2034 3 mg/Kg iv on D1 of each cycle, and oral CR6086 90 mg twice a day for 14 days

14-day cycles of combined AGEN2034 3 mg/Kg iv on D1 of each cycle, and oral CR6086 180 mg twice a day for 14 days

CR6086

AGEN2034 3 mg/Kg iv on D1 of each 14- day cycle

AGEN2034

Principal Investigator

This Phase Ib/IIa study has been designed according to a 3+3 dose escalation/dose expansion design. A dose expansion will be conducted at both the intermediate and high dose levels, if tolerated, with the purpose of generating additional and more robust safety and preliminary efficacy data. No control arm was included, as the target patient population of this study consists of patients in whom the overall survival is less than 6 months and treatment options are very limited and often poorly tolerated, making unlikely that the study results can be significantly biased.

In this study, the combination of the PGE2 inhibition (through the EP4 receptor antagonist CR6086) with the immune checkpoint blockade (through the anti-PD-1 AGEN2034) is being evaluated. CR6086 is a potent and selective, orally bioavailable, targeted immunomodulator small molecule acting as an EP4 receptor antagonist. AGEN2034 (balstilimab) is a novel, fully human monoclonal immunoglobulin G4 antibody, designed to block programmed cell death 1 (PD-1) from interacting with its ligands (PD-L) PD-L1 and PD-L2, currently being developed for the treatment of advanced malignancies. EP4 receptor antagonists turn the status of the tumor microenvironment into a favourable one, i.e. immune-responsive, representing thus a rational therapeutic approach in combination with ICIs in primarily refractory cancers.

Prospective, open label, non-randomized, single-arm (non-controlled), multiple ascending dose (dose escalation)

A Phase Ib/IIa Study of CR6086 in Combination With Balstilimab in pMMR-MSS Metastatic Colorectal Cancer Patients

An Open-label, Single-arm, Phase Ib/IIa Trial to Evaluate the Safety and Efficacy of the EP4 Receptor Antagonist CR6086 in Combination With the PD-1 Inhibitor Balstilimab (AGEN2034), in Patients With Pretreated Mismatch-repair-proficient and Microsatellite Stable Metastatic Colorectal Cancer

Proportion of patients who have achieved CR, PR, or stable disease (SD) per RECIST 1.1 / iRECIST

Proportion of patients who have achieved CR or PR per RECIST 1.1 / iRECIST

Time from first documentation of response (CR or PR) until the time of first documentation of disease progression per RECIST 1.1 / iRECIST

Time from the first dose of study drugs to the earlier date of assessment of progression per RECIST 1.1 / iRECIST, or death by any cause in the absence of progression

Proportion of patients alive and free of disease progression per RECIST 1.1 / iRECIST at specific timepoints, or death by any cause in the absence of progression

Time from the first dose of study drugs to the date of death by any cause

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase 1a/1b Study of TPST-1495 as a Single Agent and in Combination With Pembrolizumab in Subjects With Solid Tumors	NCT04344795	Solid Tumor Colorectal Canc... Non Small Cell ... Squamous Cell C... Urothelial Carc... Endometrial Can... Gastroesophagea... Gastric Adenoca... Solid Tumors Wi...	TPST-1495 twice... TPST-1495 once ... Pembrolizumab	18 Years -	Tempest Therapeutics
A Phase Ib/IIa Study of CR6086 in Combination With Balstilimab in pMMR-MSS Metastatic Colorectal Cancer Patients	NCT05205330	Refractory Meta... Solid Tumor Metastatic Micr... Mismatch Repair...	CR6086 AGEN2034	18 Years -	Rottapharm Biotech
Phase 1a/1b Study of TPST-1495 as a Single Agent and in Combination With Pembrolizumab in Subjects With Solid Tumors	NCT04344795	Solid Tumor Colorectal Canc... Non Small Cell ... Squamous Cell C... Urothelial Carc... Endometrial Can... Gastroesophagea... Gastric Adenoca... Solid Tumors Wi...	TPST-1495 twice... TPST-1495 once ... Pembrolizumab	18 Years -	Tempest Therapeutics

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