Advanced Solid Tumor, Metastatic Solid Tumors, MET Gene Alterations
Conditions
Keywords
Non Small Cell Lung, Non Small Cell Lung Cancer, Non-small cell lung cancer, NSCLC, TPX-0022, EGFR wild-type (wt), advanced non-small cell lung cancer, advanced/metastatic disease, Non-small cell lung carcinoma (NSCLC), treatment of lung cancer after first metastasis, treatment of gastric cancer after first metastasis, treatment of hepatocellular cancer after first metastasis, lung cancer, lung adenocarcinoma, Non small cell lung carcinoma, MET exon 14 deletion, MET exon 14 skipping, MET exon 14 mutation, MET mutation, MET amplification, MET inhibitor, MET dysregulation, MET activation, MET signaling, MET pathway, MET fusion, gastric cancer, hepatocellular cancer, SRC, CSF1R, cancer, first in human
Brief summary
A phase 1/2, first-in-human, open-label study of the safety, tolerability, PK, and efficacy of the novel MET/CSF1R/SRC inhibitor TPX-0022 in adult subjects with advanced or metastatic NSCLC, Gastric Cancer, or solid tumors harboring genetic alterations in MET. (SHIELD-I)
Detailed description
Dose Escalation: To evaluate the overall safety profile of TPX-0022, single and multiple dose PK profiles and preliminary efficacy in adults subjects with advanced solid tumors harboring genetic alterations in MET. Dose Expansion: To evaluate the preliminary efficacy and overall safety profile of TPX-0022 at the RP2D in defined cohorts of adult subjects in NSCLC, Gastric Cancer and advanced solid tumors harboring genetic alterations in MET.
Interventions
DRUGelzovantinib (TPX-0022)
Oral elzovantinib (TPX-0022) capsules
Sponsors
Turning Point Therapeutics, Inc.
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. Age ≥ 18 (or age ≥ 20 as required by local regulation). 2. Histological or cytological confirmation of advanced/metastatic MET exon 14 skipping mutation (METΔex14) NSCLC, MET amplified NSCLC, or MET amplified gastric cancers as determined by FISH, qPCR or NGS by local liquid biopsy or tissue, solid tumors with MET fusions or oncogenic MET mutations or MET amplified other than GI/NSCLC. 3. ECOG performance status ≤ 1. 4. Existence of measurable or evaluable disease (according to Response evaluation criteria in solid tumors \[RECIST v1.1\] criteria). 5. Subjects with asymptomatic primary CNS tumors or brain metastases are eligible for the study if they meet protocol specified criteria. 6. Adequate organ function. 7. Life expectancy ≥ 12 weeks.
Exclusion criteria
1. Locally advanced solid tumor that is a candidate for curative treatment through radical surgery and/or radiotherapy, or chemotherapy. 2. Presence or history of any other primary malignancy within the past 3 years other than a history of adequately treated basal or squamous cell carcinoma of the skin, or any adequately treated in situ carcinoma. 3. Major surgery within four weeks of the start of therapy. 4. Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of first cycle dose-limiting toxicities (DLTs) of elzovantinib | Within 28 days of the first elzovantinib dose for each patient | Evaluate the safety and tolerability of elzovantinib |
| Define the Recommended Phase 2 Dose | Approximately 48 months | Determine the maximum tolerated dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of elzovantinib |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC (area under plasma concentration time curve) of elzovantinib | Up to 72 hours post-dose | Evaluate the AUC of elzovantinib |
| Cmax (maximum plasma concentration) of TPX-0022 under different food intake conditions | Up to 72 hours post-dose | Determine the effect of food (specifically, a high-fat, high-calorie meal) on the single-dose PK (Cmax) of elzovantinib at the RP2D |
| AUC (area under plasma concentration time curve) of elzovantinib under different food intake conditions | Up to 72 hours post-dose | Determine the effect of food (specifically, a high-fat, high-calorie meal) on the single-dose PK (AUC) of elzovantinib at the RP2D |
| Preliminary Objective Response Rate (ORR) | Approximately 48 months | Determine the preliminary objective response rate (ORR) by Blinded Independent Central Review (BICR) of elzovantinib |
| Clinical benefit rate (CBR) | Approximately 48 months | Determine the CBR of elzovantinib |
| Adverse events (AEs) | Approximately 48 months | Evaluate the overall safety profile of elzovantinib |
| Duration of Response (DOR) | Approximately 48 months | Determine the DOR of elzovantinib |
| Progression free survival (PFS) | Approximately 48 months | Determine the PFS of elzovantinib |
| Intracranial tumor response | Approximately 48 months | Determine the intracranial tumor response in subjects with measurable brain metastases, as determined by BICR |
| Overall survival (OS) | Approximately 48 months | Determine efficacy and safety of elzovantinib |
| Time to response (TTR) | Approximately 48 months | Determine the TTR of elzovantinib |
| Cmax (maximum plasma concentration) of elzovantinib | Up to 72 hours post-dose | Evaluate the maximum plasma concentration of elzovantinib |
Countries
France, North Korea, South Korea, Spain, United States
Outcome results
None listed