Clinical trial NCT03993873: Study of TPX-0022 in Patients With Advanced NSCLC, Gastric Cancer or Solid Tumors Harboring Genetic Alterations in MET
Official title: A Phase 1/2 of Study of the Safety, Tolerability, Pharmacokinetics, and Efficacy of TPX-0022 in Adult Subjects With Locally Advanced or Metastatic NSCLC, Gastric Cancer, or Solid Tumors Harboring Genetic Alterations in MET
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumor
Metastatic Solid Tumors
MET Gene Alterations
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
Lead sponsor: Turning Point Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2019-06-21
Enrollment: 95
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: 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.

Eligibility criteria: 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 exclusion criteria for subjects with NSCLC with MET alterations: known oncogene mutations (eg, ALK, ROS1, KRAS, EGFR, etc.) for which there are approved therapies.
5. Additional exclusion criteria for subjects with HCC with MET alterations: liver dysfunction greater than Child-Pugh Class A.
6. Clinically significant cardiovascular disease (either active or within six months before enrollment): myocardial infarction, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (New York Heart Association Classification Class ≥ II), cerebrovascular accident or transient ischemic attack, symptomatic bradycardia, requirement for anti-arrhythmic medication. Ongoing cardiac dysrhythmias of CTCAE version 5.0 grade ≥ 2.
7. Any of the following cardiac criteria:

   * Mean resting corrected QT interval (ECG interval measured from the onset of the QRS complex to the end of the T wave) for heart rate (QTc) \> 470 msec obtained from three ECGs, using the screening clinic ECG machine-derived QTc value
   * Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval \> 250 msec)
   * Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, congenital long QT syndrome, family history of long QT syndrome, or any concomitant medication known to prolong the QT interval
8. Known clinically significant active infections not controlled with systemic treatment (bacterial, fungal, viral including HIV positivity).
9. Peripheral neuropathy ≥ Grade 2.

Primary outcomes:
measure: Incidence of first cycle dose-limiting toxicities (DLTs) of elzovantinib
timeFrame: Within 28 days of the first elzovantinib dose for each patient
measure: Define the Recommended Phase 2 Dose
timeFrame: Approximately 48 months
Secondary outcomes:
measure: Adverse events (AEs)
timeFrame: Approximately 48 months
measure: Cmax (maximum plasma concentration) of elzovantinib
timeFrame: Up to 72 hours post-dose
measure: AUC (area under plasma concentration time curve) of elzovantinib
timeFrame: Up to 72 hours post-dose
measure: Cmax (maximum plasma concentration) of TPX-0022 under different food intake conditions
timeFrame: Up to 72 hours post-dose
measure: AUC (area under plasma concentration time curve) of elzovantinib under different food intake conditions
timeFrame: Up to 72 hours post-dose
measure: Preliminary Objective Response Rate (ORR)
timeFrame: Approximately 48 months
measure: Clinical benefit rate (CBR)
timeFrame: Approximately 48 months
measure: Time to response (TTR)
timeFrame: Approximately 48 months
measure: Duration of Response (DOR)
timeFrame: Approximately 48 months
measure: Progression free survival (PFS)
timeFrame: Approximately 48 months
measure: Intracranial tumor response
timeFrame: Approximately 48 months
measure: Overall survival (OS)
timeFrame: Approximately 48 months
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Local Institution - 2102
state: California
city: Orange
country: United States
facility: Local Institution - 2108
state: California
city: Denver
country: United States
facility: Local Institution - 2105
state: Colorado
city: Chicago
country: United States
facility: Local Institution - 2111
state: Illinois
city: Boston
country: United States
facility: Local Institution - 2107
state: Massachusetts
city: Boston
country: United States
facility: Local Institution - 2109
state: Massachusetts
city: Ann Arbor
country: United States
facility: Local Institution - 2106
state: Michigan
city: Detroit
country: United States
facility: Local Institution - 2113
state: Michigan
city: Saint Louis
country: United States
facility: Local Institution - 2103
state: Missouri
city: Toledo
country: United States
facility: Local Institution - 2104
state: Ohio
city: Houston
country: United States
facility: Local Institution - 2101
state: Texas
city: Fairfax
country: United States
facility: Local Institution - 2112
state: Virginia
city: La Tronche
country: France
facility: Local Institution - 4202
state: Rhone-Alpes
city: Saint-Mandé
country: France
facility: Local Institution - 4203
state: Val-de-Marne
city: Villejuif
country: France
facility: Local Institution - 4204
state: Val-de-Marne
city: Lyon
country: France
facility: Local Institution - 4201
city: Seoul
country: Korea, Democratic People's Republic of
facility: Local Institution - 6304
city: Seoul
country: Korea, Republic of
facility: Local Institution - 6301
state: Seoul-teukbyeolsi [Seoul]
city: Seoul
country: Korea, Republic of
facility: Local Institution - 6303
city: Seoul
country: Korea, Republic of
facility: Local Institution - 6302
city: Madrid
country: Spain
facility: Local Institution - 4104
city: Madrid
country: Spain
facility: Local Institution - 4103
city: Madrid
country: Spain
facility: Local Institution - 4101
city: Pamplona
country: Spain
facility: Local Institution - 4102
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: