Clinical trial NCT05768321: Study of GEC255 in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Advanced Solid Tumors
Lead sponsor: GenEros Biopharma Ltd
Sponsor class: INDUSTRY
First posted: 2023-03-14
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of patients experiencing Dose limiting toxicities (DLTs) during the Maximum tolerated dose (MTD) evaluation period for study drug in monotherapy
timeFrame: 28 days
measure: Determine the recommended Phase II dose (RP2D) and preliminarily to develop a suitable dosing regimen
timeFrame: 24 months
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: 24 months
measure: Incidence of vital signs abnormalities
timeFrame: 24 months
measure: Incidence of ECG (PR interval, QRS complex, QT corrected interval prolonged, and QT interval corrected using Fridericia's formula) abnormalities
timeFrame: 24 months
measure: Incidence of laboratory abnormalities
timeFrame: 24 months
Secondary outcomes:
measure: All study parts, Area under the plasma concentration-time curve from time zero to time t(AUC0-t) of GEC255
timeFrame: Up to 24 months
measure: All study parts,Area under the plasma concentration-time curve from time zero to time infinity(AUC0-∞) of GEC255
timeFrame: Up to 24 months
measure: All study parts,Area under the plasma concentration-time curve over dosing interval (AUCtau) of GEC255
timeFrame: Up to 24 months
measure: All study parts,Apparent plasma clearance of drug after extravascular administration(CL/F) of GEC255
timeFrame: Up to 24 months
measure: All study parts,Terminal half-life(t½) of GEC255
timeFrame: Up to 24 months
measure: All study parts,Apparent Volume of Distribution(VZ/F) of GEC255
timeFrame: Up to 24 months
measure: All study parts,Maximum concentration (Cmax) of GEC255
timeFrame: Up to 24 months
measure: All study parts,Time to maximum plasma concentration (Tmax) of GEC255
timeFrame: Up to 24 months
measure: Overall response rate (ORR) per RECIST v1.1, by treatment
timeFrame: 24 months
measure: Disease Control Rate (DCR) per RECIST v1.1
timeFrame: 24 months
measure: Duration of Response (DOR) per RECIST v1.1
timeFrame: 24 months
measure: Progression-free survival (PFS) per RECIST v1.1
timeFrame: 24 months
measure: To evaluate Overall Survival (OS) following initiation of GEC255
timeFrame: 24 months
measure: Evaluation of gene mutations profiles
timeFrame: 24 months
Other outcomes:
Locations:
city: Chengdu
country: China
facility: China West Hospital
state: Sichuan
Study officials:
affiliation: West China Hospital
name: You Lu, MD
role: PRINCIPAL_INVESTIGATOR
References: