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

NCT05768321 | Unknown Phase 1

• 1 other identifier: GEC255-P1-01
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (6)

• 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)

  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

  24 months

• Incidence of Treatment-Emergent Adverse Events

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

  24 months

• Incidence of vital signs abnormalities

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

  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

  24 months

• Incidence of laboratory abnormalities

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

  24 months

Secondary Outcomes (14)

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

  Up to 24 months

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

  Up to 24 months

• All study parts,Area under the plasma concentration-time curve over dosing interval (AUCtau) of GEC255

  Up to 24 months

• All study parts,Apparent plasma clearance of drug after extravascular administration(CL/F) of GEC255

  Up to 24 months

• All study parts,Terminal half-life(t½) of GEC255

  Up to 24 months

Study Arms (1)

GEC255 treatment

EXPERIMENTAL

Oral tablet(s), once daily in 28-day cycles

Drug: GEC255 tablets

Interventions

GEC255 tablets DRUG

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

GEC255 treatment

Eligibility Criteria

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

You may qualify if:

• 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).
• 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)
• 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.
• 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.
• Has estimated survival period ≥ 3 months.
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1.

You may not qualify if:

• Has received KRAS inhibitor treatment (for second part only).
• 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) .
• Has had any anticancer treatments, including immunotherapy, chemotherapy, or radiotherapy within 4 weeks prior to the first dose of GEC255.
• Has gastrointestinal disorder affecting absorption (eg, gastrectomy).
• Has significant cardiovascular disease. Male subjects with corrected QT interval (QTc) ≥ 450ms, female subject with QTc ≥ 470ms
• Has primary central nervous system (CNS) tumor;
• Has unstable brain metastases with meningeal metastasis, spinal cord compression, symptomatic or requiring steroid/anti-epileptic medication 4 weeks before enrollment
• HIV positive or active infection of hepatitis B virus (HBV), hepatitis C virus (HCV), syphilis, tuberculosis
• Allergic to ingredients of GEC255; or is currently taking medicines which strongly inhibit CYP3A4.

Sponsors & Collaborators

• GenEros Biopharma Hangzhou Ltd: lead

Study Sites (1)

China West Hospital

Chengdu, Sichuan, 610000, China

RECRUITING

Study Officials

• You Lu, MD

  West China Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

XinYu Liu, PhD

CONTACT

+8619941365716; xyliu@generosbiopharma.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2023
• First Posted: March 14, 2023
• Study Start: November 4, 2021
• Primary Completion: February 28, 2024
• Study Completion: May 30, 2024
• Last Updated: March 16, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)