A Study of HC-7366 to Establish the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D)

NCT05121948 | Terminated Phase 1 FDA Drug

• 1 other identifier: HC366-FCP2111
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 7

Brief Summary

This is a first in human, multicenter, open label, Phase 1a and 1b dose-escalation and dose-expansion study to establish the maximum tolerated dose, recommended Phase 2 dose, and evaluate the safety and tolerability of QD oral dosing of HC 7366 in a dose escalating fashion in subjects with advanced solid tumors. Up to 40 subjects will be enrolled into the Phase 1a dose-escalation part of the study. The study will be conducted in the United States at approximately 7 to 10 sites. Every effort will be made to ensure approximately 50% of all subjects enrolled into Phase 1a of this study are subjects with the tumors of special interest including squamous cell carcinoma of the head and neck, colorectal cancer, non-small cell lung cancer, and transitional cell carcinoma of the bladder. Subjects with other solid tumor types are also eligible provided study selection criteria are met and they do not exceed 50% of all enrolled subjects. All subjects in Phase 1b will enroll with clear cell renal cell carcinoma. The Phase 1a study will follow a traditional 3+3 design. The starting dose level will be 10 mg QD, escalating to 20, 40, 75, 125, and 150 mg QD as safety allows. All doses are to be administered in the fasting state with water at least 1 hour before food or at least 2 hours after food. The Phase 1b dose-expansion will be at a single dose level of 75 mg based on the safety, tolerability, PK/PD results from Phase 1a to obtain additional safety and preliminary efficacy information. At the discretion of the safety monitoring committee and sponsor, the cohort may be expanded to enroll additional patients and/ or 1-2 additional cohorts will be opened. Up to 30 subjects may be enrolled in the Phase 1b portion of the study at the 75 mg dose. Replacement patients will be enrolled if necessary. Subjects will be dosed until unacceptable toxicity, disease progression per immune-related Response Evaluation Criteria in Solid Tumors, discontinuation of treatment for other protocol allowed reason (eg, subject refusal), any other administrative reasons, or after 2 years of treatment, whichever occurs first. For scheduling purposes, dosing in Phase 1a and 1b will occur in 3 week cycles and computed tomography scans will be conducted once every 6 weeks from Cycle 1/Day 1, with the first postbaseline scan after 6 weeks of dosing (precycle 3) until confirmed disease progression, death, start of new anticancer therapy, withdrawal of consent, or end of study, whichever occurs first.

Conditions

Squamous Cell Carcinoma of Head and Neck; Colo-rectal Cancer; Non Small Cell Lung Cancer; Transitional Cell Carcinoma of the Bladder; Other Solid Tumors; Clear Cell Renal Cell Carcinoma

Keywords

SCCHN; CRC; NSCLC; TCC; Phase 1; First in human; HC-7366; ccRCC

Outcome Measures

Primary Outcomes (8)

• Determination of MTD of HC-7366

  When orally administered once daily in a dose escalating fashion in subjects with selected, advanced solid tumors

  Within 18 months of last patient enrolled

• Determination of Recommended Phase 2 dose of HC-7366

  When orally administered once daily in a dose escalating fashion in subjects with selected, advanced solid tumors

  Within 18 months of last patient enrolled

• Occurrence of dose-limiting toxicities (DLTs)

  Within 18 months of last patient enrolled

• Incidence and severity of treatment-emergent adverse events (TEAEs) and treatment related TEAEs according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v 5.0

  Within 18 months of last patient enrolled

• Incidence of TEAEs leading to premature discontinuation

  Within 18 months of last patient enrolled

• Incidence of laboratory abnormalities, based on NCI CTCAE grades of hematology, serum chemistry, and urinalysis test results

  Within 18 months of last patient enrolled

• Incidence of abnormalities observed in 12 lead ECG parameters

  Within 18 months of last patient enrolled

• Incidence of abnormalities observed in vital signs measurements

  Within 18 months of last patient enrolled

Secondary Outcomes (16)

• Area under the plasma concentration versus time curve from time 0 until last measurable concentration (AUC 0-last)

  Within 24 months of last patient enrolled

• Area under the plasma concentration versus time curve from time 0 to 24 hours postdose (AUC 0-24)

  Within 24 months of last patient enrolled

• Area under the plasma concentration versus time curve from time 0 extrapolated to infinity (AUC 0-∞)

  Within 24 months of last patient enrolled

• Area under the plasma concentration versus time curve over a dosing interval (AUC 0-t)

  Within 24 months of last patient enrolled

• Peak plasma concentration (Cmax)

  Within 24 months of last patient enrolled

Study Arms (8)

Phase 1a Cohort 1 - 10 mg

EXPERIMENTAL

10 mg capsules of HC-7366 administered orally once a day in the fasting state with water at least 1 hour before food or at least 2 hours after food of each 3-week treatment cycle

Drug: HC-7366

Phase 1a Cohort 2 - 20 mg

EXPERIMENTAL

20 mg capsules of HC-7366 administered orally once a day in the fasting state with water at least 1 hour before food or at least 2 hours after food of each 3-week treatment cycle

Drug: HC-7366

Phase 1a Cohort 3 - 40 mg

EXPERIMENTAL

40 mg capsules of HC-7366 administered orally once a day in the fasting state with water at least 1 hour before food or at least 2 hours after food of each 3-week treatment cycle

Drug: HC-7366

Phase 1a Cohort 4 - 75 mg

EXPERIMENTAL

75 mg capsules of HC-7366 administered orally once a day in the fasting state with water at least 1 hour before food or at least 2 hours after food of each 3-week treatment cycle

Drug: HC-7366

Phase 1a Cohort 5 - 125 mg

EXPERIMENTAL

125 mg capsules of HC-7366 administered orally once a day in the fasting state with water at least 1 hour before food or at least 2 hours after food of each 3-week treatment cycle

Drug: HC-7366

Phase 1a Cohort 6 - 150 mg

EXPERIMENTAL

150 mg capsules of HC-7366 administered orally once a day in the fasting state with water at least 1 hour before food or at least 2 hours after food of each 3-week treatment cycle

Drug: HC-7366

Phase 1b Cohort 7 - Dose 1 Chosen for Expansion

EXPERIMENTAL

XX mg capsules of HC-7366 administered orally once a day in the fasting state with water at least 1 hour before food or at least 2 hours after food of each 3-week treatment cycle

Drug: HC-7366

Phase 1b Cohort 8 - Dose 2 Chosen for Expansion

EXPERIMENTAL

XX mg capsules of HC-7366 administered orally once a day in the fasting state with water at least 1 hour before food or at least 2 hours after food of each 3-week treatment cycle

Drug: HC-7366

Interventions

HC-7366 DRUG

HC-7366 drug product is an immediate release capsule formulation of HC-7366 potassium salt monohydrate (HC-7366-K) in a hard gelatin capsule for oral administration. Each capsule contains HC-7366-K monohydrate (the active ingredient), lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, colloidal silicon dioxide, and magnesium stearate. Capsules are supplied in 3 strengths: 10, 25, and 100 mg HC-7366 free acid equivalent.

Phase 1a Cohort 1 - 10 mg; Phase 1a Cohort 2 - 20 mg; Phase 1a Cohort 3 - 40 mg; Phase 1a Cohort 4 - 75 mg; Phase 1a Cohort 5 - 125 mg; Phase 1a Cohort 6 - 150 mg; Phase 1b Cohort 7 - Dose 1 Chosen for Expansion; Phase 1b Cohort 8 - Dose 2 Chosen for Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have a signed an informed consent form prior to any study specific procedures or treatment
• Be ≥18 years of age (male or female) at the time of consent
• Phase 1a:
• Have 1 of the following tumor types with qualifying characteristics, and have received at least 1 and no more than 5 prior lines of therapy for metastatic (stage IV) disease:
• SCCHN
• CRC
• NSCLC
• TCC
• Other solid tumors (eg, carcinoma of unknown primary) with the exception of rapidly progressing neoplasms (eg, pancreatic cancer, glioblastoma, hepatocellular carcinoma). Note: Subjects do not need to have progressed through all possible available therapies with known clinical benefit for their respective cancers to participate in this study. Note: Subjects with SCCHN, CRC, NSCLC, and TCC are a priority and should constitute as a whole, at least 50% of the enrolled population. Enrollment of all others will be capped when reaching a combined 50%, in order to maintain 18 slots for subjects with SCCHN, CRC, NSCLC, and TCC.
• Phase 1b:
• Have renal cell carcinoma with respective qualifying characteristics:
• Histological or cytological proof of component (any percentage) of clear cell RCC, excluding subjects that have any component of collecting duct or medullary histology are eligible
• Subjects with residual, but well-controlled endocrinopathy (eg, hypothyroidism) are eligible
• Subjects with metastatic or locally advanced unresectable RCC Note: Prior nephrectomy is not mandatory.
• Subjects with progressive disease after receipt of at least 2 and no more than 5 prior lines of therapy for metastatic (stage IV) disease, including but not limited to VEGF-directed tyrosine kinase inhibitors (TKIs), high-dose IL-2 , immune checkpoint inhibitors, mTOR inhibitors, or belzutifan, alone or in combination. Note: A line of therapy is considered complete once the patient has progressed following such treatment. If a treatment regimen is changed before disease progression due to toxicity, for example, this is still considered part of the same line of therapy. In addition, maintenance therapy \[that is, therapy with a different drug or drugs given to conserve an existing response or stable disease before disease progression\] is not considered an additional line of therapy.

You may not qualify if:

• Had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to the first dose of study treatment or who has not recovered from adverse reactions due to a previously administered agent or major surgery
• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
• Has a diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment. The use of physiologic doses of corticosteroids may be approved after consultation with the sponsor
• Has known history of active tuberculosis
• Has known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
• Has known active hepatitis B (eg, hepatitis B surface antigen reactive) or hepatitis C (eg, hepatitis C virus ribonucleic acid \[RNA\] \[qualitative\]) infection
• Has been diagnosed with any infectious process that would, in the opinion of the investigator, interfere with study participation, especially regarding site-specific testing and isolation requirements. This applies to viral infections including, but not limited to, severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection
• Has a history of clinically severe autoimmune disease, or history of organ transplant
• Has a history of retinitis or photosensitive skin disorders including (but not limited to) erythema multiforme, atopic eczema, psoriasis, viral exanthemata, pemphigus, and dermatitis herpetiformis
• Has known additional malignancy that is progressing or required active treatment within the previous 5 years. Exceptions include basal cell carcinoma or squamous cell carcinoma of the skin that has undergone potentially curative therapy, superficial bladder cancer, or in situ cervical cancer. Subjects with other malignancies are eligible if they were cured by surgery alone or surgery plus radiotherapy and have been continuously disease free for at least 5 years
• Has known active central nervous system metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of disease progression by imaging for at least 4 weeks prior to the first dose of study treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using systemic steroids for at least 7 days prior to study treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
• Has a history of interstitial lung disease, pneumonitis within 12 months prior to screening, or current pneumonitis
• Has an active infection requiring systemic therapy
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
• Has a clinically significant cardiovascular disease such as unstable angina, myocardial infarction, or acute coronary syndrome, symptomatic or uncontrolled arrhythmia, congestive heart failure, baseline electrocardiogram (ECG) abnormalities, including, but not limited to, QTc prolongation (as calculated using Fridericia formula) to greater than 450 ms for males or to greater than 470 ms for females, or any Class III or IV cardiac disease as defined by the New York Heart Association Functional Classification

Sponsors & Collaborators

• HiberCell, Inc.: lead
• Covance: collaborator

Study Sites (7)

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Sarah Cannon Research Institute /Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

The University of Texas M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Swedish Cancer Institute

Seattle, Washington, 98104, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Colonic Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma, Renal Cell

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Adenocarcinoma; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Jose Iglesias, MD

  Consultant Chief Medical Officer for HiberCell, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2021
• First Posted: November 16, 2021
• Study Start: February 23, 2022
• Primary Completion: February 9, 2024
• Study Completion: March 1, 2024
• Last Updated: March 8, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)