Breast Cancer, Colorectal Cancer, Endometrial Cancer, Esophageal Cancer, Head and Neck Cancer, Locally Advanced Unresectable or Metastatic Solid Tumor, Non Small Cell Lung Cancer, Ovarian Cancer, Pancreatic Cancer, Small Cell Lung Cancer
Conditions
Keywords
Solid Tumor, TP53 Y220C Mutation
Brief summary
This is a first-in-human, Phase 1/2, open-label study evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of LG00313112 in participants with advanced solid malignancies harboring a TP53 Y220C mutation
Detailed description
The objective of Phase 1 is to determine the biologically active dose range/maximum-tolerated dose (MTD) and/or recommended Phase 2 dose(s) (RP2D) of LG00313112 and to characterize the safety and tolerability of LG00313112. The objective of Phase 2 is to evaluate the antitumor activity, safety, and tolerability of LG00313112 at the dose levels selected based on the Phase 1 results.
Interventions
DRUGLG00313112
LG00313112 will be administered orally once daily (QD)
Sponsors
LG Chem
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Males and females aged 18 years or older 2. Diagnosed locally advanced unresectable or metastatic solid tumor with a TP53 Y220C mutation. 3. Documented disease progression during or after the most recent line of therapy. In addition, must be refractory to or intolerant of standard of care therapy or have no standard therapy. 4. Measurable disease per RECIST v1.1. 5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1. 6. Adequate organ function.
Exclusion criteria
1. Investigational therapy or anti-cancer therapy within 21 days or 5 half-lives prior to the first dose of study drug. 2. Radiotherapy within 14 days prior to the first dose of study drug. 3. Known brain metastases (Exception: Brain metastases are permitted if the participant is neurologically stable), leptomeningeal disease or carcinomatous meningitis. 4. Uncontrolled pleural effusion, pericardial effusion, or ascites. 5. History of myocardial infarction or unstable angina within 6 months prior to enrollment, or clinically significant cardiac disease 6. Serious infections requiring intravenous antibiotics within 14 days of first dose of study drug. 7. Active uncontrolled Hepatitis B, Hepatitis C, or human immunodeficiency virus infection 8. Acute or chronic uncontrolled renal disease, pancreatitis, or liver disease 9. History of prior organ transplant 10. Currently receiving strong Cytochrome P4503A (CYP3A4) inhibitors or inducers
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase 1: Number of participants with dose-limiting toxicities (DLTs) | Up to 21 days after treatment |
| Phase 1: Frequency of treatment-emergent adverse events (TEAEs) | Up to 12 months after treatment initiation |
| Phase 1: Frequency of serious adverse events (SAEs) | Up to 12 months after treatment initiation |
| Phase 2: objective response rate (ORR) | Up to 12 months after treatment initiation |
Secondary
| Measure | Time frame |
|---|---|
| Phase 1: Maximum observed plasma concentration (Cmax) | Approximately 12 months per participant (Approximately 77 months for Phase 1 and Phase 2) |
| Phase 1: Time to maximum observed plasma concentration (Tmax) | Approximately 12 months per participant (Approximately 77 months for Phase 1 and Phase 2) |
| Phase 1: Area under the concentration-time curve from time zero to time of last quantifiable concentration or in one dosing interval (AUC0-T, AUCtau) | Approximately 12 months per participant (Approximately 77 months for Phase 1 and Phase 2) |
| Phase 1: Terminal half-life (T1/2) | Approximately 12 months per participant (Approximately 77 months for Phase 1 and Phase 2) |
| Phase 1: ORR | Approximately 12 months per participant (Approximately 77 months for Phase 1 and Phase 2) |
| Phase 1: Time to Response (TTR) | Approximately 12 months per participant (Approximately 77 months for Phase 1 and Phase 2) |
| Phase 1: Duration of response (DOR) | Approximately 12 months per participant (Approximately 77 months for Phase 1 and Phase 2) |
| Phase 1: Disease Control Rate (DCR) | Approximately 12 months per participant (Approximately 77 months for Phase 1 and Phase 2) |
| Phase 1: Progression-free survival (PFS) | Approximately 12 months per participant (Approximately 77 months for Phase 1 and Phase 2) |
| Phase 2: Frequency of TEAEs | Approximately 12 months per participant (Approximately 77 months for Phase 1 and Phase 2) |
| Phase 2: Frequency of SAEs | Approximately 12 months per participant (Approximately 77 months for Phase 1 and Phase 2) |
| Phase 2: DOR | Approximately 12 months per participant (Approximately 77 months for Phase 1 and Phase 2) |
| Phase 2: DCR | Approximately 12 months per participant (Approximately 77 months for Phase 1 and Phase 2) |
| Phase 2: PFS | Approximately 12 months per participant (Approximately 77 months for Phase 1 and Phase 2) |
| Phase 2: Overall survival (OS) | Approximately 12 months per participant (Approximately 77 months for Phase 1 and Phase 2) |
Outcome results
None listed