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

March 14, 2023 updated by: GenEros Biopharma Hangzhou Ltd

A Phase 1 Open-Label Study to Assess the Safety, Pharmacokinetics, and Preliminary Efficacy of GEC255 Oral Tablets in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
70

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • China
    • Sichuan
      • Chengdu, Sichuan, China, 610000
        • Recruiting
        • China West Hospital
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: GEC255 treatment
Oral tablet(s), once daily in 28-day cycles
Drug: GEC255 tablets

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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of patients experiencing Dose limiting toxicities (DLTs) during the Maximum tolerated dose (MTD) evaluation period for study drug in monotherapy
Time Frame: 28 days
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
Time Frame: 24 months
Measured by the number of subjects with dose limiting toxicities
24 months
Incidence of Treatment-Emergent Adverse Events
Time Frame: 24 months
Characterized by type, frequency, severity (as graded by NCI-CTCAE version 5.0), timing, seriousness
24 months
Incidence of vital signs abnormalities
Time Frame: 24 months
Characterized by type, frequency, severity (as graded by NCI CTCAE version5.0), and timing,seriousness
24 months
Incidence of laboratory abnormalities
Time Frame: 24 months
Characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing
24 months
Incidence of ECG (PR interval, QRS complex, QT corrected interval prolonged, and QT interval corrected using Fridericia's formula) abnormalities
Time Frame: 24 months
Characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing
24 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
All study parts, Area under the plasma concentration-time curve from time zero to time t(AUC0-t) of GEC255
Time Frame: Up to 24 months
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
Time Frame: 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,Apparent plasma clearance of drug after extravascular administration(CL/F) of GEC255
Time Frame: Up to 24 months
All study parts,Apparent plasma clearance of drug after extravascular
Up to 24 months
All study parts,Terminal half-life(t½) of GEC255
Time Frame: Up to 24 months
All study parts,Terminal half-life(t½) of GEC255
Up to 24 months
All study parts,Apparent Volume of Distribution(VZ/F) of GEC255
Time Frame: Up to 24 months
All study parts,Apparent Volume of Distribution(VZ/F) of GEC255
Up to 24 months
All study parts,Maximum concentration (Cmax) of GEC255
Time Frame: Up to 24 months
All study parts,Maximum concentration (Cmax) of GEC255
Up to 24 months
All study parts,Time to maximum plasma concentration (Tmax) of GEC255
Time Frame: Up to 24 months
All study parts,Time to maximum plasma concentration (Tmax) of GEC255
Up to 24 months
Disease Control Rate (DCR) per RECIST v1.1
Time Frame: 24 months
The disease control rate is calculated as the percentage of patients with advanced or metastatic cancer who have achieved complete response, partial response and stable disease. It will be summarized along with the corresponding 95% exact CI
24 months
Duration of Response (DOR) per RECIST v1.1
Time Frame: 24 months
Duration of response is defined as the time from the date of the first documented response (CR or PR), to the date of first documented progression, or death due any cause. Estimates will use Kaplan-Meier method, and median DOR and corresponding 95% CI will be presented
24 months
Progression-free survival (PFS) per RECIST v1.1
Time Frame: 24 months
Per RECIST 1.1, PFS is defined as the time from the date of start of treatment to the date of the first documented progression. If patient has not had an event, PFS will be censored at the date of last adequate tumor assessment
24 months
To evaluate Overall Survival (OS) following initiation of GEC255
Time Frame: 24 months
OS is defined as the time from the date of start of treatment to the date of the death
24 months
All study parts,Area under the plasma concentration-time curve over dosing interval (AUCtau) of GEC255
Time Frame: Up to 24 months
All study parts,Area under the plasma concentration-time curve over dosing interval (AUCtau) of GEC255
Up to 24 months
Overall response rate (ORR) per RECIST v1.1, by treatment
Time Frame: 24 months
Overall response rate is defined as the proportion of patients with a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) according to RECIST 1.1, and will be summarized along with the corresponding 95% exact binomial confidence interval (CI)
24 months
Evaluation of gene mutations profiles
Time Frame: 24 months
Evaluation of gene mutations profiles including KRAS, STK11, KEAP1 etc in cell-free DNA (cfDNA) samples by Next-generation sequencing (NGS) method at various time points during treatment until disease progression
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
GenEros Biopharma Hangzhou Ltd

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 4, 2021

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 28, 2024

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 30, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 15, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 2, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 14, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 16, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 14, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • GEC255-P1-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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