Non Small Cell Lung CancerPhase 1/2NCT05705466
Study of Navtemadlin Plus Pembrolizumab as Maintenance Therapy in Locally Advanced and Metastatic Non-Small Cell Lung Cancer
A Phase 1/2 study testing Navtemadlin and Pembrolizumab in people with Non Small Cell Lung Cancer, run by Kartos Therapeutics, Inc..
Trial summary
This study evaluates Navtemadlin (KRT-232) in combination with Pembrolizumab as a maintenance therapy in patients with locally advanced and metastatic non small cell lung cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non Small Cell Lung Cancer
- What is being tested?
- Navtemadlin and Pembrolizumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Jun 2023to Jun 2027
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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
- ECOG 0-1
- Histologically or cytologically confirmed diagnosis of NSCLC documented as TP53WT
- Locally advanced or metastatic disease; must have completed up to 4 cycles of platinum-based chemo plus CPI and achieved a CR or PR per RECIST V1.1
- Adequate hematologic, hepatic and renal function (within 14 days)
Who cannot join
- Symptomatic or uncontrolled central nervous system (CNS) metastases
- Prior treatment with a MDM2 inhibitor
- Grade 2 or higher QTc prolongation (>480 msec per NCI-CTCAE criteria version 5.0)
- History of bleeding diathesis; major hemorrhage or intracranial hemorrhage within 24 weeks
- History of major organ transplant
- Active pneumonitis or known history of interstitial lung disease, drug-related pneumonitis, or radiation pneumonitis
- Prior radiotherapy, cytoreductive therapy, cytokine therapy or any investigational therapy within 28 days
- Medical condition, serious intercurrent illness, psychiatric condition or other circumstance that, in the Investigator's judgment could jeopardize the subject's safety, or that could interfere with study objectives
About this study
Official title: A Two-Part, Phase 1b/2, Multicenter, Open-Label, Dose Escalation and Double-Blind, Randomized, Placebo-Controlled, Dose Expansion Study of the Safety, Efficacy and Pharmacokinetics of Navtemadlin Plus Pembrolizumab as Maintenance Therapy in Subjects With Locally Advanced and Metastatic Non-Small Cell Lung Cancer
This study evaluates Navtemadlin (KRT-232) in combination with Pembrolizumab as a maintenance therapy in patients with locally advanced and metastatic non small cell lung cancer.
Read the detailed description
This is a 2 part, phase 1b/2, maintenance study for patients who have achieved a partial response (PR) or complete response (CR) after completion of up to 4 cycles of a combination platinum-based chemotherapy plus CPI regimen.
Phase 1b is a 3+3 dose escalation design that will be used to determine the maximum tolerated dose (MTD) and/or the recommended phase 2 dose (RP2D) of navtemadlin in combination with pembrolizumab. A Safety Review Committee (SRC) will review the safety data during the dose escalation to decide on dose escalation and/or exploration of intermediate doses.
Phase 2 will evaluate the efficacy and safety of the RP2D of navtemadlin plus pembrolizumab compared to navtemadlin placebo plus pembrolizumab. Each Arm will have approximately 40 subjects enrolled for a total of approximately 80 subjects. Eligible subjects will be randomized 1:1. This part of the study has a randomized, controlled, double-blind design. A stratified, permuted-block randomization scheme will be used for treatment allocation.
- Conditions
- Non Small Cell Lung Cancer
- Being tested
- Navtemadlin, Navtemadlin Placebo, Pembrolizumab
- Keywords
- Navtemadlin
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NavtemadlinDrug
Also called KRT-232
Navtemadlin is an experimental MDM2 anticancer drug taken by mouth.
Navtemadlin PlaceboDrug
Navtemadlin placebo is a placebo that is the same in appearance to navtemadlin drug taken by mouth.
PembrolizumabDrug
Also called Keytruda
Pembrolizumab is a humanized antibody used in cancer immunotherapy that will be administered intravenously
| Study group | Role | What they receive |
|---|---|---|
| Navtemadlin in combination with pembrolizumab | Experimental | Navtemadlin will be administered orally, once daily (QD), on days 1-7 in a 21-day cycle.
Pembrolizumab will be administered intravenously on Day 1 of a 21-day cycle. Receives: Drug: Navtemadlin; Drug: Pembrolizumab |
| Navtemadlin placebo in combination with pembrolizumab | Placebo comparator | Navtemadlin placebo will be administered orally, once daily (QD), on days 1-7 in a 21-day cycle.
Pembrolizumab will be administered intravenously on Day 1 of a 21-day cycle. Receives: Drug: Navtemadlin Placebo; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1b- To determine the recommended Phase 2 dose (RP2D)
The Safety Review Committee will determine the RP2D based on safety data of the combination of navtemadlin and pembrolizumab.
Measured: 21 days
Phase 2- To assess the treatment effect of navtemadlin plus pembrolizumab treatment on PFS compared with the treatment effect of navtemadlin placebo plus pembrolizumab treatment.
PFS is defined as the time from randomization date to disease progression (assessed by the Independent Review Committee [IRC] per RECIST v1.1) or death, whichever occurs first
Measured: 64 Months
Secondary outcomes (5)
Phase 1b- To characterize the pharmacokinetic (PK) profile of navtemadlin
Will determine the Maximum observed concentration (Cmax) on Cycle 1 Day 1
Measured: 1 day
Phase 1b- To characterize the pharmacokinetic (PK) profile of navtemadlin
Will determine the area under the plasma concentration versus time curve (AUC) on Cycle 1 Day 1
Measured: 1 day
Phase 1b- To characterize the pharmacokinetic (PK) profile of navtemadlin
Will determine the time of maximum plasma concentration (Tmax) on Cycle 1 Day 1
Measured: 1 day
Phase 1b- To assess the treatment effect on progression-free survival (PFS)
PFS is defined as the time from first dose date to disease progression (assessed by the IRC and Investigator per RECIST v1.1) or death, whichever occurs first
Measured: 64 Months
Phase 2- To assess the treatment effect of navtemadlin plus pembrolizumab treatment on PFS compared with the treatment effect of navtemadlin placebo plus pembrolizumab treatment.
PFS is defined as the time from randomization date to disease progression (assessed by the Investigator per RECIST v1.1) or death, whichever occurs first
Measured: 64 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2023
- Study startJun 2023 (estimated)
- Primary completionJun 2025 (estimated)
- Study completionJun 2027 (estimated)
Why it stopped: Sponsor Decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kartos Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05705466
- Sponsor's protocol ID
- KRT-232-119
- Status last verified
- Mar 2024
- First submitted
- 17 Jan 2023
- Last updated
- 22 Mar 2024
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Two-Part, Phase 1b/2, Multicenter, Open-Label, Dose Escalation and Double-Blind, Randomized, Placebo-Controlled, Dose Expansion Study of the Safety, Efficacy and Pharmacokinetics of Navtemadlin Plus Pembrolizumab as Maintenance Therapy in Subjects With Locally Advanced and Metastatic Non-Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT05705466
- Acronym / sponsor ID
- KRT-232-119
- Conditions
- Non Small Cell Lung Cancer
- Keywords
- Navtemadlin
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Sponsor Decision
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Kartos Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- Jun 2023 (estimated)
- Primary completion
- Jun 2025 (estimated)
- Study completion
- Jun 2027 (estimated)
- First posted
- 30 Jan 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates Navtemadlin (KRT-232) in combination with Pembrolizumab as a maintenance therapy in patients with locally advanced and metastatic non small cell lung cancer.
Detailed description
This is a 2 part, phase 1b/2, maintenance study for patients who have achieved a partial response (PR) or complete response (CR) after completion of up to 4 cycles of a combination platinum-based chemotherapy plus CPI regimen.
Phase 1b is a 3+3 dose escalation design that will be used to determine the maximum tolerated dose (MTD) and/or the recommended phase 2 dose (RP2D) of navtemadlin in combination with pembrolizumab. A Safety Review Committee (SRC) will review the safety data during the dose escalation to decide on dose escalation and/or exploration of intermediate doses.
Phase 2 will evaluate the efficacy and safety of the RP2D of navtemadlin plus pembrolizumab compared to navtemadlin placebo plus pembrolizumab. Each Arm will have approximately 40 subjects enrolled for a total of approximately 80 subjects. Eligible subjects will be randomized 1:1. This part of the study has a randomized, controlled, double-blind design. A stratified, permuted-block randomization scheme will be used for treatment allocation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Navtemadlin in combination with pembrolizumab | Experimental | Drug: Navtemadlin, Drug: PembrolizumabNavtemadlin will be administered orally, once daily (QD), on days 1-7 in a 21-day cycle. Pembrolizumab will be administered intravenously on Day 1 of a 21-day cycle. |
| Navtemadlin placebo in combination with pembrolizumab | Placebo comparator | Drug: Navtemadlin Placebo, Drug: PembrolizumabNavtemadlin placebo will be administered orally, once daily (QD), on days 1-7 in a 21-day cycle. Pembrolizumab will be administered intravenously on Day 1 of a 21-day cycle. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- ECOG 0-1
- Histologically or cytologically confirmed diagnosis of NSCLC documented as TP53WT
- Locally advanced or metastatic disease; must have completed up to 4 cycles of platinum-based chemo plus CPI and achieved a CR or PR per RECIST V1.1
- Adequate hematologic, hepatic and renal function (within 14 days)
Key exclusion criteria (8 listed)
- Symptomatic or uncontrolled central nervous system (CNS) metastases
- Prior treatment with a MDM2 inhibitor
- Grade 2 or higher QTc prolongation (>480 msec per NCI-CTCAE criteria version 5.0)
- History of bleeding diathesis; major hemorrhage or intracranial hemorrhage within 24 weeks
- History of major organ transplant
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 |
|---|---|---|
| NavtemadlinAlso: KRT-232Navtemadlin is an experimental MDM2 anticancer drug taken by mouth. | Drug | Navtemadlin in combination with pembrolizumab |
| Navtemadlin PlaceboNavtemadlin placebo is a placebo that is the same in appearance to navtemadlin drug taken by mouth. | Drug | Navtemadlin placebo in combination with pembrolizumab |
| PembrolizumabAlso: KeytrudaPembrolizumab is a humanized antibody used in cancer immunotherapy that will be administered intravenously | Drug | Navtemadlin in combination with pembrolizumab, Navtemadlin placebo in combination with pembrolizumab |
Primary outcome
Phase 1b- To determine the recommended Phase 2 dose (RP2D)
Time frame: 21 days
The Safety Review Committee will determine the RP2D based on safety data of the combination of navtemadlin and pembrolizumab.
Phase 2- To assess the treatment effect of navtemadlin plus pembrolizumab treatment on PFS compared with the treatment effect of navtemadlin placebo plus pembrolizumab treatment.
Time frame: 64 Months
PFS is defined as the time from randomization date to disease progression (assessed by the Independent Review Committee [IRC] per RECIST v1.1) or death, whichever occurs first
5 secondary outcomes
Phase 1b- To characterize the pharmacokinetic (PK) profile of navtemadlin
Time frame: 1 day
Phase 1b- To characterize the pharmacokinetic (PK) profile of navtemadlin
Time frame: 1 day
Phase 1b- To characterize the pharmacokinetic (PK) profile of navtemadlin
Time frame: 1 day
Phase 1b- To assess the treatment effect on progression-free survival (PFS)
Time frame: 64 Months
Phase 2- To assess the treatment effect of navtemadlin plus pembrolizumab treatment on PFS compared with the treatment effect of navtemadlin placebo plus pembrolizumab treatment.
Time frame: 64 Months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2024.
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Navtemadlin and Pembrolizumab in people with Non Small Cell Lung Cancer, run by Kartos Therapeutics, Inc..
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 4 inclusion and 8 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: withdrawn, as of the sponsor's last update on 22 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Phase 1b- To determine the recommended Phase 2 dose (RP2D) (time frame: 21 days). 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 22 Mar 2024.