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Small Molecule Inhibitor

Navtemadlin +/− Immunotherapy for Skin Cancer

Phase 1 & 2

Recruiting

Research Sponsored by Kartos Therapeutics, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

For Cohort 1, 3 and 4 patients must have failed treatment with at least one PD-1 inhibitor or PD-L1 inhibitor for metastatic MCC

ECOG performance status of 0 to 1

Must not have

For Cohort 2, subjects must not have autoimmune disease, medical conditions requiring systemic immunosuppression, prior stem cell transplant, or active infection with HBV or HCV

Grade 2 or higher QTc prolongation (>480 milli-seconds per NCI-CTCAE criteria, version 5.0)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 1 year after last subject enrolled.

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug to treat Merkel cell carcinoma, a type of skin cancer. The drug works by targeting a protein called MDM2. Previous treatments haven't worked for patients with this cancer, so this trial is testing to see if this new drug is effective.

Who is the study for?

This trial is for patients with Merkel Cell Carcinoma who have tried at least one anti-PD-1 or anti-PD-L1 therapy, except for one group that hasn't had these treatments. Participants must be in good physical condition (ECOG 0-1), have measurable cancer lesions, and proper organ function. Those with major organ transplants, certain autoimmune diseases, previous MDM2 antagonist therapies, untreated brain metastases, or significant heart rhythm issues cannot join.

What is being tested?

The study tests KRT-232 alone or combined with Avelumab in different groups of MCC patients based on their prior treatments. KRT-232 targets a protein called MDM2 to fight cancer cells. The goal is to see if this new approach works better for those who haven't responded well to existing immunotherapies.

What are the potential side effects?

Potential side effects include typical reactions from immune-based cancer therapies such as fatigue, skin reactions, inflammation-related symptoms affecting various organs and possible blood abnormalities due to the novel mechanism of action targeting MDM2.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have tried at least one PD-1 or PD-L1 inhibitor for my metastatic MCC without success.

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I can carry out all my usual activities without help.

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My MCC is p53WT positive according to a certified test.

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I have had at least one chemotherapy treatment before.

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I have not had chemotherapy before.

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My MCC is p53WT positive according to a lab test.

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My Merkel cell carcinoma is confirmed and can be measured.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I don't have autoimmune diseases, need for immunosuppressants, had a stem cell transplant, or active hepatitis B or C.

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My heart's electrical cycle is longer than normal.

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I have brain metastases that have not been treated.

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I have been treated with MDM2 or p53 therapies before.

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I have had a major organ transplant.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 1 year after last subject enrolled.

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~1 year after last subject enrolled.

This trial's timeline: 3 weeks for screening, Varies for treatment, and 1 year after last subject enrolled. for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Cohort 1 Part 1: To determine the KRT-232 RP2D.

Cohort 1 Part 2: To determine the objective response rate (ORR) in subjects with p53WT MCC who have failed anti-PD-1 or anti-PDL-1 immunotherapy

Cohort 2 Part 1: To determine the KRT-232 RP2D in combination with avelumab

+3 more

Secondary study objectives

To determine Progression-free survival (PFS)

To determine clinical benefit rate (CBR)

To determine overall survival (OS)

+2 more

Side effects data

From 2020 Phase 2 trial • 19 Patients • NCT03006848

17%

Musculoskeletal and connective tissue disorders

11%

Injury, poisoning and procedural complications

Endocrine disorders

General disorders and administration site conditions

Metabolism and nutrition disorders

Nervous system disorders

Investigations

Cardiac disorders

Gastrointestinal disorders

Infections and infestations

Immune system disorders

Blood and lymphatic system disorders

Neoplasms benign, malignant and unspecified

Respiratory, thoracic and mediastinal disorders

Renal and urinary disorders

Skin and subcutaneous tissue disorders

100%

80%

60%

40%

20%

Study treatment Arm

Avelumab

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

11Treatment groups

Experimental Treatment

Group I: Cohort 4Experimental Treatment1 Intervention

KRT-232 will be administered orally, once daily (QD) per Cohort 1 RP2D dose and schedule.

Group II: Cohort 3Experimental Treatment1 Intervention

KRT-232 will be administered orally, once daily (QD) per Cohort 1 RP2D dose and schedule.

Group III: Cohort 2, Arm 2 KRT-232 in combination with avelumabExperimental Treatment2 Interventions

KRT-232 will be administered orally, once daily (QD) on Days 1-7, in combination with avelumab 800 mg IV on Day 1 and 15 in a 28-day cycle.

Group IV: Cohort 2, Arm 1 KRT-232 in combination with avelumabExperimental Treatment2 Interventions

KRT-232 will be administered orally, once daily (QD) on Days 1-5, in combination with avelumab 800 mg IV on Day 1 and 15 in a 28-day cycle.

Group V: Cohort 2 ExpansionExperimental Treatment2 Interventions

KRT-232 will be administered orally, once daily (QD) per RP2D dose and schedule, in combination with avelumab 800 mg IV on Day 1 and 15 in a 28-day cycle.

Group VI: Cohort 1, Arm 5Experimental Treatment1 Intervention

KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 28-day cycle.

Group VII: Cohort 1, Arm 3Experimental Treatment1 Intervention

KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 21-day cycle.

Group VIII: Cohort 1, Arm 2bExperimental Treatment1 Intervention

KRT-232 will be administered orally, once daily (QD) on Days 1-5 in a 28-day cycle.

Group IX: Cohort 1, Arm 1bExperimental Treatment1 Intervention

KRT-232 will be administered orally, once daily (QD) on Days 1-5 in a 23-day cycle.

Group X: Cohort 1, Arm 1Experimental Treatment1 Intervention

KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 21-day cycle.

Group XI: Cohort 1 ExpansionExperimental Treatment1 Intervention

KRT-232 will be administered orally, once daily (QD) per Cohort 1 RP2D dose and schedule.