A Study of HC-5404-FU to Establish the Maximum Tolerated Dose (MTD)

Summary

Study HC-404-FCP-2011 is a first in human, Phase 1a, multi-center, open-label study to establish the maximum tolerated dose (MTD) and evaluate the safety and tolerability of oral dosing of HC-5404-FU in a dose-escalating fashion. Up to 36 qualified subjects at 3 to 5 US sites, who have specific tumor types of renal cell carcinoma (RCC), gastric cancer (GC), metastatic breast cancer (MBC), small cell lung cancer (SCLC), and other solid tumors (e.g., non-small cell lung cancer, colorectal cancer, carcinoma of unknown primary) with the exception of rapidly progressing neoplasms (e.g., pancreatic cancer, glioblastoma, hepatocellular carcinoma) will receive HC-5404-FU. Every effort will be made to ensure approximately 50% of all subjects enrolled will be subjects with RCC and GC. The starting dose level is 25 mg twice daily (BID), escalating to 50, 100, and 200 mg BID as safety allows, following the Bayesian Optimal Interval (BOIN) design. The safety monitoring committee (SMC) will evaluate the DLTs and cumulative safety and PK data at the end of each cohort. Based on the SMC recommendations after a comprehensive review of PK and safety data for 200 mg BID dose, higher dose levels will be evaluated, starting with 400 mg BID. The dose will escalate to 600 mg and then 900 mg following the BOIN design starting with 1 subject at each escalated dose, until the MTD is reached or the sponsor or SMC declares the dose most appropriate for clinical development. This Phase 1a will be expanded into a Phase 1b/2a study through a protocol amendment and will then assess the dose and tumor type(s) selected in Phase 1a as the most appropriate for further clinical development. Subjects will be dosed until unacceptable toxicity, disease progression per immune-related Response Evaluation Criteria in Solid Tumors (iRECIST), subject withdrawal, any other administrative reasons, or after 2 years of treatment, whichever occurs first. Efficacy will be assessed via Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1); computed tomography (CT) scans will be conducted every 6 weeks. Safety, including occurrence of dose-limiting toxicities (DLTs), pharmacokinetics (PK), and biomarker parameters will also be assessed.

Conditions

• Renal Cell Carcinoma
• Gastric Cancer
• Metastatic Breast Cancer
• Small-cell Lung Cancer
• Other Solid Tumors

Interventions

DRUG

HC-5404-FU

HC 5404-FU (hemi fumarate salt of HC 5404) is a novel, highly selective, and potent PERK inhibitor. Preclinical pharmacological studies demonstrated high specificity of HC 5404-FU to PERK and decreased viability of tumor cells. HC 5404-FU will be orally administered BID every day with food or within 30 minutes of completing a meal, starting at 25 mg, with doses escalating to 50, 100, 200, 400, 600, and 900 mg BID as safety allows for each 3-week treatment cycle.

Sponsors & Collaborators

• Covance

  collaborator INDUSTRY

• HiberCell, Inc.

  lead INDUSTRY

Principal Investigators

• Jose Iglesias, MD · Consultant Chief Medical Officer for HiberCell, Inc.

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-06-08

Primary Completion

2023-12-07

Completion

2024-01-30

FDA Drug

Yes

Countries

• United States

Study Locations