KRAS Mutation-Related TumorsPhase 1/2NCT05071183
A Study of Repotrectinib in Combination With Other Anticancer Therapies for the Treatment of Subjects With KRAS-Mutant Solid Tumors
A Phase 1/2 study testing TPX-0005 and Trametinib in people with KRAS Mutation-Related Tumors and Metastatic Solid Tumor, run by Turning Point Therapeutics, Inc. at 6 sites in United States.
Trial summary
A Phase 1b/2 Study of Repotrectinib in Combination with Other Anticancer Therapies for the Treatment of Subjects with KRAS-Mutant Advanced Solid Tumors (TRIDENT-2) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- KRAS Mutation-Related Tumors, Metastatic Solid Tumor, Advanced Solid Tumor
- What is being tested?
- TPX-0005 and Trametinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 6 sitesUnited States
- Study dates
- 23 Sep 2021to 1 Mar 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 as required by local regulation).
- Histological or cytological confirmation of unresectable or metastatic solid tumor malignancy harboring a KRAS mutation.
- No more than 3 prior standard treatments appropriate for tumor type and stage of disease.
- ECOG performance status ≤ 1.
- Existence of measurable disease (according to Response evaluation criteria in solid tumors [RECIST v1.1] criteria).
- Subjects with asymptomatic CNS metastases and/or asymptomatic leptomeningeal carcinomatosis are eligible.
- Adequate organ function.
Who cannot join
- Major surgery within four weeks of the start of treatment.
- Previous other cancer requiring treatment within the previous two years.
- Clinically significant cardiovascular disease.
- Any of the following cardiac criteria:
- Mean resting corrected QT interval (QTc) > 470 msec obtained from three ECGs and any factors that increase the risk of QTc prolongation or arrhythmic events
- Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG
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- Known clinically significant active infections not controlled with systemic treatment (bacterial, fungal, viral including HIV positivity).
- Gastrointestinal disease or other malabsorption syndromes that would impact drug absorption.
- Subjects being treated with or anticipating the need for treatment with strong CYP3A inhibitors or inducers.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Local Institution - 2101
California City, California, 90033
Local Institution - 2109
California City, California, 92663
Local Institution - 2106
Denver, Colorado, 80218
Local Institution - 2107
Houston, Texas, 77030
Local Institution - 2108
Nashville, Tennessee, 37203
Local Institution - 2102
Virginia Beach, Virginia, 22031
About this study
Official title: A Phase 1b/2 Study of Repotrectinib in Combination With Other Anticancer Therapies for the Treatment of Subjects With KRAS-Mutant Advanced Solid Tumors (TRIDENT-2)
A Phase 1b/2 Study of Repotrectinib in Combination with Other Anticancer Therapies for the Treatment of Subjects with KRAS-Mutant Advanced Solid Tumors (TRIDENT-2)
Read the detailed description
Phase 1 Dose Escalation: To evaluate tolerability of repotrectinib at increasing dose levels in combination with other anticancer therapies for the treatment of subjects with locally advanced or metastatic KRAS-mutant solid tumors
Phase 2 Efficacy Evaluation: Investigate the anti-tumor efficacy and safety of repotrectinib in combination with other anticancer therapies for the treatment of patients with locally advanced or metastatic KRAS-mutant solid tumors.
- Being tested
- TPX-0005, Trametinib
- Keywords
- KRAS, KRAS-mutant, Metastatic Solid Tumor, Advanced Solid Tumor, Advanced/metastatic disease
- Medical subject headings
- Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TPX-0005Drug
Also called repotrectinib
Oral TPX-0005 capsules
TrametinibDrug
Also called Mekinist
Oral trametinib tablets
| Study group | Role | What they receive |
|---|---|---|
| TPX-0005 + Trametinib | Experimental | TPX-0005 + Trametinib Dose Escalation and Dose Expansion
Dose escalation: KRAS G12D mutant advanced solid tumors. Dose expansion: KRAS G12D locally advanced or metastatic NSCLC Receives: Drug: TPX-0005; Drug: Trametinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Dose Limiting Toxicities
Number of participants with first cycle DLTs to determine Mean Tolderable Dose (MTD) and/or RP2D.
A DLT is defined as an adverse event (AE) or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications that meets the criteria defined in each subprotocol.
The MTD is defined as the highest dose level of repotrectinib given in combination with other anticancer therapy observed to cause a DLT in fewer than 33% of the treated subjects in the first treatment cycle (i.e., Cycle 1).
Measured: From initial dose to end of first cycle of treatment, approximately 28 days
Secondary outcomes (7)
Overall Response Rate (ORR) Assessed the Investigator Using RECIST v1.1.
The ORR will be defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR). A confirmed response is a response that persists on a repeat imaging performed at least 4 weeks after initial documentation of response. Participants with a confirmed objective response (CR or PR) will be referred to as responders.
Radiographic confirmation of objective tumor response (CR or PR) or disease progression will be based on RECIST v1.1. The ORR will be reported as the percentage of responders by RECIST v1.1 along with the corresponding two-sided 95% Clopper-Pearson exact CI.
Complete Response (CR) = Disappearance of all target lesions Partial Response (PR) = >=30% decrease in the sum diameters of target lesions.
Measured: From screening to end of treatment approximately 10 months
Cmax of Repotrectinib
Cmax is defined as maximum plasma concentration of the drug.
Measured: At Cycle 1 Day 1 and Cycle 1 Day 22
Tmax of Repotrecitinib
Tmax is defined is the time to maximum plasma concentration
Measured: At Cycle 1 Day 1 and Cycle 1 Day 22
AUC 0-24 of Repotrecitinib
Area under the plasma concentration time-curve. AUC from time 0 to 24 hours after dose.
Measured: At Cycle 1 Day 1 and Cycle 1 Day 22
Cmax of Trametinib
Cmax is defined as maximum plasma concentration of the drug.
Measured: At Cycle 1 Day 1 and Cycle 1 Day 22
Tmax of Trametinib
Tmax is defined is the time to maximum plasma concentration
Measured: At Cycle 1 Day 1 and Cycle 1 Day 22
AUC 0-24 of Trametinib
Area under the plasma concentration time-curve. AUC from time 0 to 24 hours after dose.
Measured: At Cycle 1 Day 1 and Cycle 1 Day 22
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2021
- Study start23 Sep 2021
- Primary completion1 Mar 2023
- Study completion1 Mar 2023
Why it stopped: Inability to achieve and optimize a dose that could provide a positive benefit risk profile
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 KRAS Mutation-Related TumorsStudies 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
- 9 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
- NCT05071183
- Sponsor's protocol ID
- CA127-1025
- Other IDs
- CA127-1025, TPX-0005-13
- Status last verified
- Mar 2024
- First submitted
- 13 Sep 2021
- Last updated
- 2 Apr 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Expanded access
- Available
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b/2 Study of Repotrectinib in Combination With Other Anticancer Therapies for the Treatment of Subjects With KRAS-Mutant Advanced Solid Tumors (TRIDENT-2)
- ClinicalTrials.gov ID
- NCT05071183
- Acronym / sponsor ID
- CA127-1025
- Keywords
- KRAS, KRAS-mutant, Metastatic Solid Tumor, Advanced Solid Tumor, Advanced/metastatic disease
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Inability to achieve and optimize a dose that could provide a positive benefit risk profile
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Turning Point Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 23 Sep 2021 (actual)
- Primary completion
- 1 Mar 2023 (actual)
- Study completion
- 1 Mar 2023 (actual)
- First posted
- 8 Oct 2021 (actual)
- Results
- Posted 2 Apr 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 1b/2 Study of Repotrectinib in Combination with Other Anticancer Therapies for the Treatment of Subjects with KRAS-Mutant Advanced Solid Tumors (TRIDENT-2)
Detailed description
Phase 1 Dose Escalation: To evaluate tolerability of repotrectinib at increasing dose levels in combination with other anticancer therapies for the treatment of subjects with locally advanced or metastatic KRAS-mutant solid tumors
Phase 2 Efficacy Evaluation: Investigate the anti-tumor efficacy and safety of repotrectinib in combination with other anticancer therapies for the treatment of patients with locally advanced or metastatic KRAS-mutant solid tumors.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TPX-0005 + Trametinib | Experimental | Drug: TPX-0005, Drug: TrametinibTPX-0005 + Trametinib Dose Escalation and Dose Expansion Dose escalation: KRAS G12D mutant advanced solid tumors. Dose expansion: KRAS G12D locally advanced or metastatic NSCLC |
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 as required by local regulation).
- Histological or cytological confirmation of unresectable or metastatic solid tumor malignancy harboring a KRAS mutation.
- No more than 3 prior standard treatments appropriate for tumor type and stage of disease.
- ECOG performance status ≤ 1.
- Existence of measurable disease (according to Response evaluation criteria in solid tumors [RECIST v1.1] criteria).
Key exclusion criteria (9 listed)
- Major surgery within four weeks of the start of treatment.
- Previous other cancer requiring treatment within the previous two years.
- Clinically significant cardiovascular disease.
- Any of the following cardiac criteria:
- Mean resting corrected QT interval (QTc) > 470 msec obtained from three ECGs and any factors that increase the risk of QTc prolongation or arrhythmic events
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-0005Also: repotrectinibOral TPX-0005 capsules | Drug | TPX-0005 + Trametinib |
| TrametinibAlso: MekinistOral trametinib tablets | Drug | TPX-0005 + Trametinib |
Primary outcome
Number of Participants With Dose Limiting Toxicities
Time frame: From initial dose to end of first cycle of treatment, approximately 28 days
Number of participants with first cycle DLTs to determine Mean Tolderable Dose (MTD) and/or RP2D. A DLT is defined as an adverse event (AE) or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications that meets the criteria defined in each subprotocol. The MTD is defined as the highest dose level of repotrectinib given in combination with other anticancer therapy observed to cause a DLT in fewer than 33% of the treated subjects in the first treatment cycle (i.e., Cycle 1).
7 secondary outcomes
Overall Response Rate (ORR) Assessed the Investigator Using RECIST v1.1.
Time frame: From screening to end of treatment approximately 10 months
Cmax of Repotrectinib
Time frame: At Cycle 1 Day 1 and Cycle 1 Day 22
Tmax of Repotrecitinib
Time frame: At Cycle 1 Day 1 and Cycle 1 Day 22
AUC 0-24 of Repotrecitinib
Time frame: At Cycle 1 Day 1 and Cycle 1 Day 22
Cmax of Trametinib
Time frame: At Cycle 1 Day 1 and Cycle 1 Day 22
Tmax of Trametinib
Time frame: At Cycle 1 Day 1 and Cycle 1 Day 22
AUC 0-24 of Trametinib
Time frame: At Cycle 1 Day 1 and Cycle 1 Day 22
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 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.
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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
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing TPX-0005 and Trametinib in people with KRAS Mutation-Related Tumors and Metastatic Solid Tumor, run by Turning Point Therapeutics, Inc. at 6 sites in United States.
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 9 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 2 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. 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 2 Apr 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 (time frame: From initial dose to end of first cycle of treatment, approximately 28 days). 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 2 Apr 2024.