Non Small Cell Lung CancerPhase 1/2NCT04161391
Study of TPX-0046, A RET/SRC Inhibitor in Adult Subjects With Advanced Solid Tumors Harboring RET Fusions or Mutations
A Phase 1/2 study testing TPX-0046 in people with Non Small Cell Lung Cancer and Medullary Thyroid Cancer, run by Turning Point Therapeutics, Inc. at 21 sites in 2 countries.
Trial summary
A phase 1/2, first-in-human, open-label study to determine the safety, tolerability, PK, and preliminary efficacy of the novel RET/SRC inhibitor TPX-0046 in adult subjects with advanced or metastatic solid tumors harboring RET mutations or alterations. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non Small Cell Lung Cancer, Medullary Thyroid Cancer, RET Gene Mutation
- What is being tested?
- TPX-0046
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 21 sitesin 2 countries
- Study dates
- 6 Dec 2019to 22 May 2023
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 (or age ≥ 20 as required by local regulation).
- Histological or cytological confirmation of advanced/metastatic solid tumors harboring oncogenic RET fusions or mutations, who either have disease progression on, or are intolerant to standard therapy; OR are ineligible for standard therapy or for whom no standard therapy exists; OR are unlikely to tolerate or derive clinical benefit from standard therapy in the opinion of the Investigator OR have declined standard therapy.
- ECOG performance status ≤ 1.
- Existence of measurable or evaluable disease (according to Response evaluation criteria in solid tumors [RECIST v1.1] criteria).
- Subjects with asymptomatic primary CNS tumors or brain metastases are eligible for the study if they meet protocol specified criteria.
- Adequate organ function.
- Life expectancy ≥ 12 weeks.
Who cannot join
- Locally advanced solid tumor that is a candidate for curative treatment through radical surgery and/or radiotherapy, or chemotherapy.
- Presence or history of any other primary malignancy within 3 years other than a history of adequately treated basal or squamous cell carcinoma of the skin, or any adequately treated in situ carcinoma.
- Major surgery within four weeks of the start of therapy.
- 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.
- 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
Show all 12Show fewer
- 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
- Known clinically significant active infections not controlled with systemic treatment (bacterial, fungal, viral including HIV positivity).
- Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact drug absorption.
- Subjects being treated with or anticipating the need for treatment with strong CYP3A4 inhibitors or inducers.
- Subjects with current or anticipated need for drugs that are sensitive CYP2C9 substrates with narrow therapeutic indices.
Trial locations and contacts
21 sites in 2 countries.
21 sites in 2 countries
United States20 sites
Local Institution - 2124
Ann Arbor, Michigan, 48109-5000
Local Institution - 2127
Atlanta, Georgia, 30322
Local Institution - 2122
Aurora, Colorado, 80045
Massachusetts General Hospital
Boston, Massachusetts, 02114
University of Chicago Medicine
Chicago, Illinois, 60637
SCRI - HealthOne Denver
Denver, Colorado, 80218
Local Institution - 2131
Detroit, Michigan, 48201
Local Institution - 2135
Fairfax, Virginia, 22031
Local Institution - 2120
Houston, Texas, 77030-3721
Baylor College of Medicine - Baylor Heart Clinic
Houston, Texas, 77030
Mayo Clinic - Jacksonville
Jacksonville, Florida, 32224
Local Institution - 2129
La Jolla, California, 92093
Memorial Sloan Kettering Cancer Center
New York, New York, 10021
Local Institution - 2128
Orange, California, 92868
Local Institution - 2137
Philadelphia, Pennsylvania, 19111
Mayo Clinic - Arizona
Rochester, Minnesota, 55905
Mayo Clinic - Rochester
Rochester, Minnesota, 55905
Local Institution - 2132
Seattle, Washington, 98195
Local Institution - 2130
Tampa, Florida, 33612-9416
Local Institution - 2126
Washington D.C., District of Columbia, 20007
About this study
Official title: A Phase 1/2 Study of TPX-0046, A Novel Oral RET/SRC Inhibitor in Adult Subjects With Advanced/Metastatic Solid Tumors Harboring Oncogenic RET Fusions or Mutations
A phase 1/2, first-in-human, open-label study to determine the safety, tolerability, PK, and preliminary efficacy of the novel RET/SRC inhibitor TPX-0046 in adult subjects with advanced or metastatic solid tumors harboring RET mutations or alterations. The study consists of three portions: 1) Phase 1 Dose Escalation and Food Effect Sub-study, and 2) Phase 1 dose expansion and 3) Phase 2 efficacy evaluation.
Read the detailed description
Phase 1 Dose Escalation and Dose Expansion: To evaluate the overall safety profile, characterize the PK profiles and assess the preliminary efficacy of TPX-0046 in adults subjects with advanced solid tumors harboring oncogenic RET fusions or mutations.
Food Effect Sub-Study: To determine the effect of food on PK of TPX-0046 in adult subjects with advanced or metastatic solid tumors harboring oncogenic RET fusions or mutations.
Phase 2 Efficacy Evaluation: To determine the overall safety and anti-tumor efficacy of TPX-0046 in defined cohorts of subjects with advanced/metastatic solid tumors harboring oncogenic RET fusions or mutations.
- Conditions
- Non Small Cell Lung Cancer, Medullary Thyroid Cancer, RET Gene Mutation, Metastatic Solid Tumor, Advanced Solid Tumor
- Being tested
- TPX-0046
- Keywords
- Non small cell lung cancer, Non-small cell lung cancer, NSCLC, Medullary Thyroid Cancer, MTC, RET gene mutation, RET gene alteration, Advanced non small cell lung cancer, Advanced/metastatic disease, lung cancer, lung adenocarcinoma, Metastatic solid tumor, Advanced Solid Tumors, RET gene fusion, RET inhibitor, SRC, TPX-0046, Thyroid cancer
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Carcinoma, Medullary, Neoplasm Metastasis, Lung Neoplasms, Adenocarcinoma of Lung, Thyroid Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TPX-0046Drug
Oral TPX-0046 capsules
| Study group | Role | What they receive |
|---|---|---|
| TPX-0046 | Experimental | The Phase 1 part of the study will determine the safety, tolerability, PK, MTD, and RP2D of TPX-0046.
The food-effect sub-study determines the effect of food on a dose of TPX-0046 at the RP2D dose level.
The Phase 2 part of the study will determine the safety, tolerability, PK, and preliminary efficacy in specific cohorts.
Phase 2 Cohorts:
* Cohort I (NSCLC + RET fusion, RET TKI Therapy Naive)
* Cohort II (NSCLC + RET fusion, RET TKI Therapy Pre-treated)
* Cohort III (MTC + RET mutation, RET TKI Therapy Naive)
* Cohort IV (MTC + RET mutation, RET TKI Therapy Pre-treated)
* Cohort V (advanced/metastatic tumor with RET fusion or mutation, RET TKI Therapy Naive)
* Cohort VI (advanced/metastatic tumor with RET fusion or mutation, RET TKI Therapy Pre-Treated) Receives: Drug: TPX-0046 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Dose Limiting Toxicities (DLTs) of TPX-0046
Participants are eligible for DLT evaluation if they experience a DLT after at least one dose of TPX-0046, or do not experience a DLT after taking at least 75% of the doses expected during the DLT evaluation period. Some adverse events, graded using Common Terminology for Adverse Events (CTCAE) v. 5.0, for defining DLTs include:
- Toxicities resulting in an excessive number of missed doses;
- Hematologic: CTCAE grade ≥ 4 neutropenia, CTCAE grade ≥ 4 platelet count decrease, CTCAE grade ≥ 4 anemia, CTCAE grade ≥ 3 febrile neutropenia;
- Renal: CTCAE grade ≥ 3 creatinine increase;
- Hepatic: CTCAE grade ≥ 3 total bilirubin elevation;
- Pancreatic: CTCAE grade 3 serum amylase or lipase increased with clinical symptoms or any grade ≥ serum amylase;
- Cardiac: CTCAE grade ≥ 3;
- Other AEs: CTCAE grade 3 vomiting or nausea that does not resolve to grade ≤ 1 within 4 days despite optimal anti-emetic therapy or any grade ≥ 4 vomiting
Measured: 28 days following the first highest dose of the dose regimen administered in Cycle 1
Maximum Tolerated Dose (MTD) of TPX-0046
The MTD is defined as the highest dose level of TPX-0046 observed to cause a dose limiting toxicity (DLT) in fewer than 33% of the treated participants in the first treatment cycle (ie, Cycle 1, 28 days).
Measured: 28 days following the first highest dose of the dose regimen administered in Cycle 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2019
- Study start6 Dec 2019
- Primary completion22 May 2023
- Study completion22 May 2023
Why it stopped: Adverse change in the risk/benefit.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Non Small Cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- Turning Point Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04161391
- Sponsor's protocol ID
- CA129-1036
- Other IDs
- CA129-1036, TPX-0046-01
- Status last verified
- May 2024
- First submitted
- 11 Nov 2019
- Last updated
- 13 Jun 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Study of TPX-0046, A Novel Oral RET/SRC Inhibitor in Adult Subjects With Advanced/Metastatic Solid Tumors Harboring Oncogenic RET Fusions or Mutations
- ClinicalTrials.gov ID
- NCT04161391
- Acronym / sponsor ID
- CA129-1036
- Conditions
- Non Small Cell Lung Cancer, Medullary Thyroid Cancer, RET Gene Mutation, Metastatic Solid Tumor, Advanced Solid Tumor
- Keywords
- Non small cell lung cancer, Non-small cell lung cancer, NSCLC, Medullary Thyroid Cancer, MTC, RET gene mutation, RET gene alteration, Advanced non small cell lung cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Adverse change in the risk/benefit.
- Enrolment
- 41 participants (actual)
- Lead sponsor
- Turning Point Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 6 Dec 2019 (actual)
- Primary completion
- 22 May 2023 (actual)
- Study completion
- 22 May 2023 (actual)
- First posted
- 13 Nov 2019 (actual)
- Results
- Posted 13 Jun 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A phase 1/2, first-in-human, open-label study to determine the safety, tolerability, PK, and preliminary efficacy of the novel RET/SRC inhibitor TPX-0046 in adult subjects with advanced or metastatic solid tumors harboring RET mutations or alterations. The study consists of three portions: 1) Phase 1 Dose Escalation and Food Effect Sub-study, and 2) Phase 1 dose expansion and 3) Phase 2 efficacy evaluation.
Detailed description
Phase 1 Dose Escalation and Dose Expansion: To evaluate the overall safety profile, characterize the PK profiles and assess the preliminary efficacy of TPX-0046 in adults subjects with advanced solid tumors harboring oncogenic RET fusions or mutations.
Food Effect Sub-Study: To determine the effect of food on PK of TPX-0046 in adult subjects with advanced or metastatic solid tumors harboring oncogenic RET fusions or mutations.
Phase 2 Efficacy Evaluation: To determine the overall safety and anti-tumor efficacy of TPX-0046 in defined cohorts of subjects with advanced/metastatic solid tumors harboring oncogenic RET fusions or mutations.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TPX-0046 | Experimental | Drug: TPX-0046The Phase 1 part of the study will determine the safety, tolerability, PK, MTD, and RP2D of TPX-0046. The food-effect sub-study determines the effect of food on a dose of TPX-0046 at the RP2D dose level. The Phase 2 part of the study will determine the safety, tolerability, PK, and preliminary efficacy in specific cohorts. Phase 2 Cohorts: * Cohort I (NSCLC + RET fusion, RET TKI Therapy Naive) * Cohort II (NSCLC + RET fusion, RET TKI Therapy Pre-treated) * Cohort III (MTC + RET mutation, RET TKI Therapy Naive) * Cohort IV (MTC + RET mutation, RET TKI Therapy Pre-treated) * Cohort V (advanced/metastatic tumor with RET fusion or mutation, RET TKI Therapy Naive) * Cohort VI (advanced/metastatic tumor with RET fusion or mutation, RET TKI Therapy Pre-Treated) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age ≥ 18 (or age ≥ 20 as required by local regulation).
- Histological or cytological confirmation of advanced/metastatic solid tumors harboring oncogenic RET fusions or mutations, who either have disease progression on, or are intolerant to standard therapy; OR are ineligible for standard therapy or for whom no standard therapy exists; OR are unlikely to tolerate or derive clinical benefit from standard therapy in the opinion of the Investigator OR have declined standard therapy.
- ECOG performance status ≤ 1.
- Existence of measurable or evaluable disease (according to Response evaluation criteria in solid tumors [RECIST v1.1] criteria).
- Subjects with asymptomatic primary CNS tumors or brain metastases are eligible for the study if they meet protocol specified criteria.
Key exclusion criteria (12 listed)
- Locally advanced solid tumor that is a candidate for curative treatment through radical surgery and/or radiotherapy, or chemotherapy.
- Presence or history of any other primary malignancy within 3 years other than a history of adequately treated basal or squamous cell carcinoma of the skin, or any adequately treated in situ carcinoma.
- Major surgery within four weeks of the start of therapy.
- 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.
- Any of the following cardiac criteria:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TPX-0046Oral TPX-0046 capsules | Drug | TPX-0046 |
Primary outcome
Number of Participants With Dose Limiting Toxicities (DLTs) of TPX-0046
Time frame: 28 days following the first highest dose of the dose regimen administered in Cycle 1
Participants are eligible for DLT evaluation if they experience a DLT after at least one dose of TPX-0046, or do not experience a DLT after taking at least 75% of the doses expected during the DLT evaluation period. Some adverse events, graded using Common Terminology for Adverse Events (CTCAE) v. 5.0, for defining DLTs include: * Toxicities resulting in an excessive number of missed doses; * Hematologic: CTCAE grade ≥ 4 neutropenia, CTCAE grade ≥ 4 platelet count decrease, CTCAE grade ≥ 4 anemia, CTCAE grade ≥ 3 febrile neutropenia; * Renal: CTCAE grade ≥ 3 creatinine increase; * Hepatic: CTCAE grade ≥ 3 total bilirubin elevation; * Pancreatic: CTCAE grade 3 serum amylase or lipase increased with clinical symptoms or any grade ≥ serum amylase; * Cardiac: CTCAE grade ≥ 3; * Other AEs: CTCAE grade 3 vomiting or nausea that does not resolve to grade ≤ 1 within 4 days despite optimal anti-emetic therapy or any grade ≥ 4 vomiting
Maximum Tolerated Dose (MTD) of TPX-0046
Time frame: 28 days following the first highest dose of the dose regimen administered in Cycle 1
The MTD is defined as the highest dose level of TPX-0046 observed to cause a dose limiting toxicity (DLT) in fewer than 33% of the treated participants in the first treatment cycle (ie, Cycle 1, 28 days).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jun 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- BMS Clinical Trial InformationLink provided by the sponsor.
- BMS Clinical Trial Patient RecruitingLink provided by the sponsor.
- FDA Safety Alerts and RecallsLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Non Small Cell Lung Cancer
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingObservational study
A Prospective ,Multicenter ,Non-interventional ,Real-world Study Observing Changes in Molecular Markers Osimertinib Targeted Therapy in EGFRm NSCLC
Non Small Cell Lung Cancer
RecruitingPhase 3
A Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)
Non-Small Cell Lung Cancer (NSCLC)
Active, not recruitingPhase 2
Datopotamab Deruxtecan (Dato-DXd, DS-1062a) in Advanced and/or Unresectable Non-Small Cell Lung Cancer
Metastatic Lung Cancer, Advanced Non Small Cell Lung Cancer
Not yet recruitingPhase 1/2
STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
21 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing TPX-0046 in people with Non Small Cell Lung Cancer and Medullary Thyroid Cancer, run by Turning Point Therapeutics, Inc. at 21 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in United States, South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Jun 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Dose Limiting Toxicities (DLTs) of TPX-0046 (time frame: 28 days following the first highest dose of the dose regimen administered in Cycle 1). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jun 2024.