Study of GEC255 in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation

GenEros Biopharma Hangzhou Ltd70 enrolled

Overview

The overall objective of this Phase 1 study is to evaluate the safety, Pharmacokinetics (PK), and anti-tumor activity of daily oral dosing with GEC255 tablets in subjects with advanced solid tumor with Kirsten Rat Sarcoma (KRAS) p.G12C mutation. To determine the recommended Phase 2 dose (RP2D) based on assessments of multiple dose escalation and expansion in target cohorts.

This First-in-human dose escalation and expansion study of GEC255 tablets in patients with advanced solid tumors with KRAS p.G12C mutation aims to evaluate the safety, tolerability, PK and preliminary efficacy of orally administered GEC255, to determine the MTD, DLT (if exists) and RP2D, and explore the potential biomarker associated with efficacy or drug resistance.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Advanced Solid Tumors

Interventions

GEC255 tabletsDRUG

Part 1: Dose escalation After initial starting dose cohort, daily dosages in subsequent cohorts are determined by cohort review committee. Part 2: Dose expansion Daily oral dosage RP2D based on data from Part 1

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Has histologically or cytologically confirmed advance tumors with KRAS p.G12C mutation and has poor response to standard of care therapy or intolerant to standard of care therapies (chemotherapy, targeting therapy or immunotherapy). 2. As assessed by the investigator, the subject must have at least one measurable lesion that meets the definition of Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 (subjects with only non-target lesions are allowed to be included in the dose escalation phase) 3. For the second part, subjects with non-small cell lung cancer must have received at least first-line platinum-based chemotherapy and/or immunotherapy /or anti-vascular therapy; subjects with colorectal cancer must have previously received second-line or above therapies and have tumor progression or recurrence. Except for KRAS mutations and other driver gene-positive subjects, they must have received at least first-line approved targeted therapy(if any) and are assessed by researchers that they hardly benefit from existing targeted therapies. 4. Has adequate organ functions, and had no blood transfusion, Erythropoietin (EPO), colony stimulating factor (CSF) or other supportive medical treatment within 14 days prior to the first dosing of GEC255. 5. Has estimated survival period ≥ 3 months. 6. Fertile female subjects must have negative serological test for pregnancy. All subjects must agree to take contraceptive measures from Informed Consent Form (ICF) signing till 3 months after last treatment. 7. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1. Exclusion Criteria: 1. Has received KRAS inhibitor treatment (for second part only). 2. Participated in other interventional clinical trials 4 weeks before enrollment or within 5 half-lives of the trial drug used last time (whichever is longer) . 3. Has had any anticancer treatments, including immunotherapy, chemotherapy, or radiotherapy within 4 weeks prior to the first dose of GEC255. 4. Has gastrointestinal disorder affecting absorption (eg, gastrectomy). 5. Has significant cardiovascular disease. Male subjects with corrected QT interval (QTc) ≥ 450ms, female subject with QTc ≥ 470ms 6. Has primary central nervous system (CNS) tumor; 7. Has unstable brain metastases with meningeal metastasis, spinal cord compression, symptomatic or requiring steroid/anti-epileptic medication 4 weeks before enrollment 8. HIV positive or active infection of hepatitis B virus (HBV), hepatitis C virus (HCV), syphilis, tuberculosis 9. Allergic to ingredients of GEC255; or is currently taking medicines which strongly inhibit CYP3A4.

Locations (1)

China West Hospital

Chengdu, Sichuan, China

RECRUITING

Outcomes

Primary Outcomes

Number of patients experiencing Dose limiting toxicities (DLTs) during the Maximum tolerated dose (MTD) evaluation period for study drug in monotherapy

characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study drug(Part 1)

Time frame: 28 days

Determine the recommended Phase II dose (RP2D) and preliminarily to develop a suitable dosing regimen

Measured by the number of subjects with dose limiting toxicities

Time frame: 24 months

Incidence of Treatment-Emergent Adverse Events

Characterized by type, frequency, severity (as graded by NCI-CTCAE version 5.0), timing, seriousness

Time frame: 24 months

Incidence of vital signs abnormalities

Characterized by type, frequency, severity (as graded by NCI CTCAE version5.0), and timing,seriousness

Time frame: 24 months

Incidence of ECG (PR interval, QRS complex, QT corrected interval prolonged, and QT interval corrected using Fridericia's formula) abnormalities

Characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing

Time frame: 24 months

Incidence of laboratory abnormalities

Characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing

Time frame: 24 months

Secondary Outcomes

All study parts, Area under the plasma concentration-time curve from time zero to time t(AUC0-t) of GEC255

Central Contacts

XinYu Liu, PhD

CONTACT

+8619941365716 xyliu@generosbiopharma.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.