Phase I/IIa Study of H002 in NSCLC With Active EGFR Mutation

NCT05519293 | Recruiting Phase 1 FDA Drug

• 1 other identifier: H002-101
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 4

Brief Summary

This is a phase I/IIa, open-label, dose-escalation and expansion study to evaluate the safety, tolerability, PK and preliminary anti-tumor activity of H002 when given orally in patients with active EGFR mutation locally advanced or metastatic non-small cell lung cancer (NSCLC). The study will contain two parts: Part A is dose escalation phase (i.e., Phase I) and Part B is dose expansion phase (i.e., Phase IIa).

Conditions

Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (3)

• DOSE ESCALATION PHASE：Incidence of dose-limiting toxicities (DLTs) at Cycle 0 and Cycle1. Incidence and severity of treatment-emergent adverse events (TEAEs), with severity determined according to National Cancer Institute (NCI) CTCAE v5.0.

  To evaluate the safety and tolerability of H002 and to determine the maximal tolerable dose (MTD), or if possible, a dose/exposure predicted to result in optimal biological dose (OBD) or recommended phase II dose (RP2D).

  At the end of Cycle 1 (include 4 days in Cycle 0 and 21 days in Cycle1)

• DOSE EXPANSION PHASE：Objective Response Rate (ORR)

  To obtain a preliminary evaluation of the anti-tumor activity at the selected dose(s) of H002 when given orally as determined according to RECIST v1.1.

  Up to approximately 30 months

• DOSE EXPANSION PHASE：Incidence and severity of TEAEs, with severity determined according to NCI CTCAE v5.0.

  To evaluate the safety at the selected dose(s) of H002 when given orally.

  Up to approximately 30 months

Secondary Outcomes (10)

• Peak Plasma Concentration (Cmax)

  Up to approximately 30 months

• Time to reach maximum concentration (Tmax)

  Up to approximately 30 months

• Area under the plasma concentration versus time curve (AUC)

  Up to approximately 30 months

• Time for half the drug concentration to be eliminated（t1/2）

  Up to approximately 30 months

• DOSE ESCALATION PHASE：Objective Response Rate (ORR)

  Up to approximately 30 months

Study Arms (6)

20 mg QD, oral

EXPERIMENTAL

H002 20mg QD, orally administered in fasting state, receive a single dose of H002 orally, followed by a 4-day washout period. Then, the same dose of H002 will be administered QD until disease progression or not tolerated.

Drug: H002

40 mg QD, oral

EXPERIMENTAL

H002 40mg QD, orally administered in fasting state, receive a single dose of H002 orally, followed by a 4-day washout period. Then, the same dose of H002 will be administered QD until disease progression or not tolerated.

Drug: H002

80 mg QD, oral

EXPERIMENTAL

H002 80mg QD, orally administered in fasting state, receive a single dose of H002 orally, followed by a 4-day washout period. Then, the same dose of H002 will be administered QD until disease progression or not tolerated.

Drug: H002

150 mg QD, oral

EXPERIMENTAL

H002 150mg QD, orally administered in fasting state, receive a single dose of H002 orally, followed by a 4-day washout period. Then, the same dose of H002 will be administered QD until disease progression or not tolerated.

Drug: H002

250 mg QD, oral

EXPERIMENTAL

H002 250mg QD, orally administered in fasting state, receive a single dose of H002 orally, followed by a 4-day washout period. Then, the same dose of H002 will be administered QD until disease progression or not tolerated.

Drug: H002

350 mg QD, oral

EXPERIMENTAL

H002 350mg QD, orally administered in fasting state, receive a single dose of H002 orally, followed by a 4-day washout period. Then, the same dose of H002 will be administered QD until disease progression or not tolerated.

Drug: H002

Interventions

H002 DRUG

Small molecule, Capsule

150 mg QD, oral; 20 mg QD, oral; 250 mg QD, oral; 350 mg QD, oral; 40 mg QD, oral; 80 mg QD, oral

Eligibility Criteria

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

You may qualify if:

• Males or females aged ≥ 18 years at time of signing informed consent form (ICF).
• Histological or cytological confirmed diagnosis of unresectable locally advanced or metastatic NSCLC.
• Subjects must have NSCLC harboring one or more active EGFR mutations known to be associated with EGFR-TKI sensitivity (including, but not limited to Del19 and L858R).
• Part A: All subjects may provide tumor sample to central laboratory to analyze the EGFR mutation status according to their own willingness;
• Part B: All subjects must provide tumor sample to central laboratory to analyze the EGFR mutation status. And subjects must have NSCLC harboring EGFR C797S mutation.
• Note: Tumor sample can be either an archival sample or a sample obtained by pretreatment biopsy prior to H002 treatment.
• Subjects must have radiological documented disease progression while on a previous continuous treatment with osimertinib or another third-generation EGFR-TKI as well as disease progression on the last treatment administered prior to enrolling in the study.
• Presence of at least one measurable lesion according to RECIST v1.1 per investigator assessment.
• ECOG performance status of 0-1.
• Life expectancy ≥ 12 weeks.
• Adequate hematologic and organ function per protocol.
• Women of childbearing potential (WOCBP) and fertile males with WOCBP partners must use highly effective contraception per protocol throughout the study. WOCBP must have a negative serum and/or urine pregnancy test result within 7 days prior to the first dose of H002.
• Signed ICF, and this must be obtained before the performance of any protocol-specific procedures.

You may not qualify if:

• Treatment with any of the following:
• Prior treatment with an EGFR-TKI within 8 days or approximately 5 × t1/2 prior to the first dose of H002, whichever is longer; Prior treatment with immunotherapy or biotherapy within 4 weeks prior to the first dose of H002; Radiotherapy (palliative radiotherapy is completed at least 2 weeks prior to the first dose of H002 can be enrolled) within 4 weeks prior to the first dose of H002; Herbal therapy that has anti-tumor effects within 2 weeks prior to the first dose of H002; Mitomycin and nitrosourea within 6 weeks prior to the first dose of H002; Oral fluorouracil such as tegafur and capecitabine within 2 weeks prior to the first dose of H002; Chemotherapy (except for mitomycin, nitrosourea, and fluorouracil oral drugs), or other anti-tumor drugs for the treatment of NSCLC within 4 weeks or approximately 5 × t1/2 prior to the first dose of H002, whichever is longer.
• Subjects with EGFR exon 20 insertion mutations only.
• Prior marketed and/or investigational treatment for EGFR C797S mutation (including, but not limited to BTP-661411, TQB3804 and BLU-945).
• Is currently participating and receiving investigational therapy or using an investigational device, or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks or 5 × t1/2 of the investigational product, whichever is longer, prior to the first dose of H002.
• Is expected to require any other form of anti-tumor therapy while on study.
• Unresolved toxicity greater than CTCAE v5.0 Grade 1 from prior anti-tumor therapy.
• ≥ CTCAE v5.0 Grade 2 skin toxicity at screening.
• Treatment with strong inhibitors, strong inducers and sensitive substrates of CYP3A4, substrates and inhibitors for P-glycoprotein (P-gp), as well as substrates for breast cancer resistance protein (BCRP) within 2 weeks prior to the first dose of H002, or anticipation of need for such drugs during study treatment.
• Uncontrollable pleural effusion, ascites, or pericardial effusion.
• Subjects who have symptomatic brain metastases, meningeal metastasis or spinal cord compression.
• Subjects who have a chronic or active infection that required systemic treatment within 2 weeks prior to the first dose of H002.
• Subjects who have gastrointestinal disorders that will affect oral administration or the investigator judges that the absorption of H002 will be interfered.
• History of hypersensitivity to active or inactive excipients of H002 or drugs with a similar chemical structure or class to H002.
• Subjects who received a diagnosis of, and/or tested positive at screening for human immunodeficiency virus (HIV).

Sponsors & Collaborators

• RedCloud Bio: lead
• Parexel: collaborator

Study Sites (4)

Valkyrie Clinical Trials

Los Angeles, California, 90067, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Columbia University

New York, New York, 10032, United States

RECRUITING

NEXT Virginia

Fairfax, Virginia, 22031, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Louis Zhang

  RedCloud Bio

  STUDY DIRECTOR

Central Study Contacts

Anna Chen

CONTACT

+886 2 2176-9685; Anna.Chen@parexel.com

Study Design

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

Model Details: Dose-escalation and Expansion

Study Record Dates

• First Submitted: August 3, 2022
• First Posted: August 29, 2022
• Study Start: December 15, 2022
• Primary Completion: February 28, 2025
• Study Completion: February 28, 2025
• Last Updated: April 11, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)