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Treatments are given in 21 day cycles. For each cycle, treatment includes:

* PLX3397 at a dose of 600 mg/day taken by mouth in the form of 100-200 mg gelcaps
* Eribulin at dose of 1.4 mg/m2 given intravenously on days 1 and 8.

Treatments are given in 21 day cycles. For each cycle, treatment includes:

* PLX3397 at a dose of 800 mg/day taken by mouth in the form of 100-200 mg gelcaps
* Eribulin at dose of 1.4 mg/m2 given intravenously on days 1 and 8

Treatments are given in 21 day cycles. For each cycle, treatment includes:

* PLX3397 at a dose of 1000 mg/day taken by mouth in the form of 100-200 mg gelcaps
* Eribulin at dose of 1.4 mg/m2 given intravenously on days 1 and 8

Treatment begins with a 7 day Lead-in phase of PLX3397 alone, followed by 21 day cycles of PLX3397 in combination with eribulin.

Lead-in phase treatment:

* PLX3397 at a dose of 800 mg/day given by mouth in the form of 100-200 mg gelcaps for 5 days followed by 2 days of rest.

Treatment given in each 21 day cycle:

* PLX3397 at a dose of 800 mg/day given by mouth in the form of 100-200 mg gelcaps for 5 days followed by 2 days of rest, repeated weekly
* Eribulin at dose of 1.4 mg/m2 given intravenously on days 1 and 8

Dosage Form: 100 mg or 200 mg capsules, Dosage: 400 - 1000 mg, oral administration

PLX3397

Dosage Form: 1 mg per 2 mL (0.5 mg per mL); Solution (clear, colorless, sterile, packaged in glass vial) Dosage: 1.4 mg/m2, 2-5 min IV, Day 1, 8 q21 days

Eribulin

Hope S. Rugo, MD

The purpose of the Phase 1b portion of the study is to determine the best dose of PLX3397 when given in combination with standard dose eribulin (Halaven™). The purpose of the Phase 2 portion of the study is to find out what effects, good and/or bad, these drugs have on patients and their metastatic breast cancer.

This is a nonrandomized, open label phase Ib/II study evaluating the safety and efficacy of eribulin in combination with PLX3397, a novel CSF1 inhibitor, in patients with metastatic breast cancer. The phase II portion of this trial will be limited to patients with triple negative disease.

The phase I portion of this trial is a dose escalation of PLX3397 to determine the maximum tolerated dose (MTD) of PLX3397 when given in combination with standard dose eribulin. Patients will be enrolled in cohorts of three, using the dose levels and plan outlined in the statistical section, with 6 patients enrolled at the MTD. All patients with accessible tumor will be required to have a tumor biopsy at study start before starting therapy. Pharmacokinetics of PLX3397 and eribulin, and blood levels of CSF1 will be obtained as outlined in section 14. To allow rapid accrual to phase Ib, and an earlier start to the phase II trial, patients will be enrolled in phase I with both hormone receptor positive and negative disease, and at any line of therapy assuming eligibility criteria are otherwise met.

Dose limiting toxicity (DLT) will be defined as any treatment-related toxicity meeting the criteria below and occurring within the first 21 days of combination therapy. Patients must receive at least 14 days of PLX3397 and 2 doses of eribulin during the first cycle in order to be considered evaluable for DLT (unless the missed doses are due to a DLT).

Patients in each cohort will be followed for at least 3 weeks (one full cycle) before opening accrual to the next dose level. If one patient in any cohort develops a DLT, an additional 3 patients will be enrolled at that level. If no additional toxicities occur in the six patients, then this particular dose would be used for the phase II trial, and the next higher dose would be considered the MTD. A minimum of 12 and maximum of 24 patients will be enrolled in the phase I study. The phase II trial will not open until the last patient in the phase I study has been followed for at least 3 weeks.

The phase II portion of this trial will evaluate progression free survival (PFS) in patients with Triple negative breast cancer (TNBC) treated with PLX3397 and eribulin, using the dose of PLX3397 determined in the phase Ib study in a two-step design. Please see the statistical section for details regarding enrollment and statistical design. Treatment is preceded by a 5 to 7 day lead-in phase, in which patients will take PLX3397 alone daily. Patients with accessible tumor will undergo a core biopsy of tumor before the start of PLX3397 treatment, and then a fine needle aspiration or core biopsy will be performed on the day of or the day before the start of eribulin (day -1 to day 0).

Phase Ib/II Study of PLX 3397 and Eribulin in Patients With Metastatic Breast Cancer

Enhancing Efficacy of Chemotherapy in Triple Negative/Basal-Like Breast Cancer by Targeting Macrophages: A Multicenter Phase Ib/II Study of PLX 3397 and Eribulin in Patients With Metastatic Breast Cancer

The MTD was determined using a standard dose-escalation schema with 3 to 6 participants per cohort (3+3 design) for participants enrolled in Phase 1b. The starting dose level of PLX3397 was 600 mg/day and was raised in successive cohorts up to a dose of 1000 mg/day. Participants in each Phase Ib cohort were followed for dose limiting toxicities (DLTs) within the first 21 days of combination therapy and had to receive at least 14 days of PLX3397 and 2 doses of eribulin during the first cycle in order to be considered evaluable for DLT (unless the missed doses were due to a DLT). A toxicity was considered a DLT if it was treatment related and met specific requirements for type of toxicity and severity assessed according to Common Terminology Criteria for Adverse Events (CTCAE) version 4. The MTD was defined as the lowest dose level at which 2 or more participants in a cohort experienced a DLT. The dose level just below the MTD was selected for Phase 2.

DLTs are select treatment related toxicities described in the protocol that were Grade 3 or 4 in severity per CTCAE v4, occurring within the first 21 days of combination therapy for patients enrolled in Phase Ib (for example, Grade 3 thrombocytopenia with significant bleeding, Grade 4 neutropenia lasting more than 5 days, or any Grade 3 or higher non-hematologic toxicity other than alopecia unless clearly unrelated to treatment). Grade 3 and 4 toxicities are considered severe and may be life threatening. Participants had to receive at least 14 days of PLX3397 and 2 doses of eribulin during the first cycle in order to be considered evaluable for DLT (unless the missed doses were due to a DLT). A treatment delay of greater than 7 days for PLX3397 or inability to get two doses of eribulin in the first cycle due to toxicity that was unrelated to cancer worsening or other illness was considered a DLT.

Progression-free survival (PFS) at 3 months is defined as the proportion of participants in the combined Phase II cohorts that are alive and progression-free 90 days after Study Day 1, from the first administration of PLX3397 with eribulin. Duration of PFS is defined as the time from Study Day 1 to the earlier of disease progression or death due to any cause. These analyses are designed to include only objective progression events per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. PFS will be estimated as a simple percentage based upon the results of the 3 month tumor assessment. Participants for whom this assessment is not performed will be included as failures, even if known to be alive at this time point. Confidence intervals will be provided.

The objective response rate (ORR) is defined as the proportion of patients for whom the best overall response at the time of data cutoff is confirmed complete response (CR) or confirmed partial response (PR) as assessed per Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 criteria. The analysis of ORR employed the Per Protocol population. Patients who did not have any post-baseline tumor assessments were counted as non-responders.

Duration of response is defined as the time from first documentation of objective response that is subsequently confirmed to progressive disease (PD) by the criteria or death due to any cause. Responders who have not been documented to have progressed or died at time of data cutoff will be right censored at the last available adequate tumor assessment. Median duration of response and its associated confidence interval will be estimated using the Kaplan-Meier method.

Time to progression will be estimated using the Kaplan-Meier method. Efficacy responses, disease progression and relapse classified based on RECIST v1.1 criteria will be used to determine progression. Time to progression will be calculated from the first administration of PLX3397 with eribulin. Participants who do not have disease progression will be censored at the date of the last evaluation for study disease or at the time of initiation of the new therapy, whichever is earlier. Patients lacking any response assessment after randomization will be censored at Day 1

Susan G. Komen Breast Cancer Foundation

Plexxikon

Hope Rugo, MD

Clinical Professor

Treatments are given in 21 day cycles. For each cycle, treatment includes:

* PLX3397 at a dose of 600 mg/day taken by mouth in the form of 100-200 mg gelcaps
* Eribulin at dose of 1.4 mg/m2 given intravenously on days 1 and 8.

PLX3397: Dosage Form: 100 mg or 200 mg capsules, Dosage: 600mg, oral administration

Eribulin: Dosage Form: 1 mg per 2 mL (0.5 mg per mL); Solution (clear, colorless, sterile, packaged in glass vial) Dosage: 1.4 mg/m2, 2-5 min IV, Day 1, 8 q21 days

Phase Ib/1: 600 mg/Day PLX3397 Combined With Eribulin

Treatments are given in 21 day cycles. For each cycle, treatment includes:

* PLX3397 at a dose of 400 mg/day taken by mouth in the form of 100-200 mg gelcaps
* Eribulin at dose of 1.4 mg/m2 given intravenously on days 1 and 8.

PLX3397: Dosage Form: 100 mg or 200 mg capsules, Dosage: 400mg, oral administration

Eribulin: Dosage Form: 1 mg per 2 mL (0.5 mg per mL); Solution (clear, colorless, sterile, packaged in glass vial) Dosage: 1.4 mg/m2, 2-5 min IV, Day 1, 8 q21 days

Phase Ib/2: 400 mg/Day PLX3397 Combined With Eribulin

Treatments are given in 21 day cycles. For each cycle, treatment includes:

* PLX3397 at a dose of 600 mg/day taken by mouth in the form of 100-200 mg gelcaps
* Eribulin at dose of 1.4 mg/m2 given intravenously on days 1 and 8.

PLX3397: Dosage Form: 100 mg or 200 mg capsules, Dosage: 600 mg, oral administration

Eribulin: Dosage Form: 1 mg per 2 mL (0.5 mg per mL); Solution (clear, colorless, sterile, packaged in glass vial) Dosage: 1.4 mg/m2, 2-5 min IV, Day 1, 8 q21 days

Phase Ib/3: 600 mg/Day PLX3397 Combined With Eribulin

Treatments are given in 21 day cycles. For each cycle, treatment includes:

* PLX3397 at a dose of 800 mg/day taken by mouth in the form of 100-200 mg gelcaps
* Eribulin at dose of 1.4 mg/m2 given intravenously on days 1 and 8

PLX3397: Dosage Form: 100 mg or 200 mg capsules, Dosage: 800 mg, oral administration

Eribulin: Dosage Form: 1 mg per 2 mL (0.5 mg per mL); Solution (clear, colorless, sterile, packaged in glass vial) Dosage: 1.4 mg/m2, 2-5 min IV, Day 1, 8 q21 days

Phase Ib/4: 800 mg/Day PLX3397 Combined With Eribulin

Phase Ib/5: 800 mg/Day PLX3397 Combined With Eribulin

Treatments are given in 21 day cycles. For each cycle, treatment includes:

* PLX3397 at a dose of 1000 mg/day taken by mouth in the form of 100-200 mg gelcaps
* Eribulin at dose of 1.4 mg/m2 given intravenously on days 1 and 8

PLX3397: Dosage Form: 100 mg or 200 mg capsules, Dosage: 1000 mg, oral administration

Eribulin: Dosage Form: 1 mg per 2 mL (0.5 mg per mL); Solution (clear, colorless, sterile, packaged in glass vial) Dosage: 1.4 mg/m2, 2-5 min IV, Day 1, 8 q21 days

Phase Ib/6: 1000 mg/Day PLX3397 Combined With Eribulin

Treatment begins with a 7 day Lead-in phase of PLX3397 alone, followed by 21 day cycles of PLX3397 in combination with eribulin.

Lead-in phase treatment:

* PLX3397 at a dose of 1000 mg/day given by mouth in the form of 100-200 mg gelcaps for 5 days followed by 2 days of rest.

Treatment given in each 21 day cycle:

* PLX3397 at a dose of 1000 mg/day given by mouth in the form of 100-200 mg gelcaps for 5 days followed by 2 days of rest, repeated weekly
* Eribulin at dose of 1.4 mg/m2 given intravenously on days 1 and 8

PLX3397: Dosage Form: 100 mg or 200 mg capsules, Dosage: 1000 mg, oral administration

Eribulin: Dosage Form: 1 mg per 2 mL (0.5 mg per mL); Solution (clear, colorless, sterile, packaged in glass vial) Dosage: 1.4 mg/m2, 2-5 min IV, Day 1, 8 q21 days

Phase II/1: 1000 mg/Day PLX3397 Combined With Eribulin

Treatment begins with a 7 day Lead-in phase of PLX3397 alone, followed by 21 day cycles of PLX3397 in combination with eribulin.

Lead-in phase treatment:

* PLX3397 at a dose of 800 mg/day given by mouth in the form of 100-200 mg gelcaps for 5 days followed by 2 days of rest.

Treatment given in each 21 day cycle:

* PLX3397 at a dose of 800 mg/day given by mouth in the form of 100-200 mg gelcaps for 5 days followed by 2 days of rest, repeated weekly
* Eribulin at dose of 1.4 mg/m2 given intravenously on days 1 and 8

PLX3397: Dosage Form: 100 mg or 200 mg capsules, Dosage: 800 mg, oral administration

Eribulin: Dosage Form: 1 mg per 2 mL (0.5 mg per mL); Solution (clear, colorless, sterile, packaged in glass vial) Dosage: 1.4 mg/m2, 2-5 min IV, Day 1, 8 q21 days

Phase II/2: 800 mg/Day PLX3397 Combined With Eribulin

Treatments were given in 21 day Cycles. For each cycle, participants received 600 mg/day of PLX3397 in 100-200 mg gelcaps, by mouth daily \& Eribulin 1.4 mg/m2 intravenously on days 1 and 8.

Treatments were given in 21 day Cycles. For each cycle, participants received 400 mg/day of PLX3397 in 100-200 mg gelcaps, by mouth daily \& Eribulin 1.1 mg/m2 intravenously on days 1 and 8.

Treatments were given in 21 day Cycles. For each cycle, participants received 800 mg/day of PLX3397 in 100-200 mg gelcaps, by mouth daily \& Eribulin 1.4 mg/m2 intravenously on days 1 and 8.

Treatments were given in 21 day Cycles. For each cycle, participants received 1000 mg/day of PLX3397 in 100-200 mg gelcaps, by mouth daily \& Eribulin 1.4 mg/m2 intravenously on days 1 and 8.

Treatment began with a 7 day Lead-in Phase, consisting of 1000 mg/day PLX3397 given by mouth for 5 days followed by 2 days of rest (no PLX3397). Then combination treatment was given in 21 day cycles. For each cycle, participants received 1000 mg/day of PLX3397 by mouth in the form of 100-200 mg gelcaps for 5 days followed by 2 days of rest repeated weekly and Eribulin at 1.4 mg/m2 intravenously on days 1 and 8.

Treatment began with a 7 day Lead-in Phase, consisting of 800 mg/day PLX3397 given by mouth for 5 days followed by 2 days of rest (no PLX3397). Then combination treatment was given in 21 day cycles. For each cycle, participants received 800 mg/day of PLX3397 by mouth in the form of 100-200 mg gelcaps for 5 days followed by 2 days of rest repeated weekly and Eribulin at 1.4 mg/m2 intravenously on days 1 and 8.

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Dr. Hope Rugo, MD

Phase Ib:

21 day treatment cycle: PLX3397 100-200 mg gelcaps, by mouth daily \& Eribulin 1.4 mg/m2 intravenously, day 1 and 8

* Cohort 1: 600 mg/day
* Cohort 2: 800 mg/day
* Cohort 3: 1000 mg/day

Phase Ib: Eribulin in Combination With PLX3397

Maximum Tolerated Dose (MTD) of PLX3397 Given in Combination With Standard Dose Eribulin in Participants With Metastatic Breast Cancer (Phase 1b)

Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) (Phase Ib)

Treatment began with a 7 day Lead-in Phase, consisting of 800 mg or 1000 mg/day PLX3397 given by mouth for 5 days followed by 2 days of rest (no PLX3397). Then combination treatment was given in 21 day cycles. For each cycle, participants received 800 mg or 1000mg /day of PLX3397 by mouth in the form of 100-200 mg gelcaps for 5 days followed by 2 days of rest repeated weekly and Eribulin at 1.4 mg/m2 intravenously on days 1 and 8.

Phase II: PLX3397 Combined With Eribulin

Both Phase II Cohorts were combined for this planned analysis. Only 31 participants in Phase II obtained an objective progression event per RECIST v1.1 criteria at month 3

Percentage of Total Phase II Participants With Chemotherapy Pre-Treated Triple Negative Metastatic Breast Cancer Who Are Progression Free at 3 Months

Both Phase II Cohorts were combined for this planned analysis. Only 31 participants in Phase II obtained an objective event per RECIST v1.1

Objective Response Rate (ORR) (Phase II)

Both Phase II Cohorts were combined for this planned analysis. Only 5 participants in Phase II obtained an objective response

Median Duration of Response (Phase II)

Both Phase II Cohorts were combined for this planned analysis. Only 31 participants in Phase II obtained an objective progression event per RECIST v1.1 criteria

Median Time to Disease Progression (Phase II)

Phase II/2: 800 mg/Day PLX3397 Lead In+Combined With Eribulin

Overall Study

Symptoms and General Pathology

Immune System Diseases

Blood and Lymph Conditions

Behaviors and Mental Disorders

Nervous System Diseases

Rare Diseases

Syndrome

Mastocytosis

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Leukemia, Myelomonocytic, Chronic

Leukemia, Myelomonocytic, Juvenile

Myelodysplastic Syndromes

Hypersensitivity

Hematologic Neoplasms

Myeloproliferative Disorders

Aggression

Soft Tissue Neoplasms

Urticaria

Hematologic Diseases

Mastocytosis, Systemic

Neoplasms, Connective Tissue

Leukemia, Mast-Cell

Urticaria Pigmentosa

Immune Complex Diseases

Neoplasms by Histologic Type

Dementia

Aberrant Motor Behavior in Dementia

Behavioral Symptoms

Neoplasms, Connective and Soft Tissue

Mast Cell Activation Disorders

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Chronic Myelomonocytic Leukemia

Juvenile Myelomonocytic Leukemia

Chronic Graft Versus Host Disease

Acute Graft Versus Host Disease

Chronic Myeloproliferative Disorders

Systemic Mastocytosis

Antigen-Antibody Complex

Bezuclastinib is administered as tablets to be taken orally, continuously in 28-day cycles.

bezuclastinib

Hina Jolin, PharmD

Rachael Easton, MD, Ph.D.

This is an open-label, two-part Phase 2 study investigating CGT9486 for the treatment of patients with Advanced Systemic Mastocytosis (AdvSM), including patients with Aggressive SM (ASM), SM with Associated Hematologic Neoplasm (SM-AHN), and Mast Cell Leukemia (MCL).

There are two parts to this study, including Part I, Dose Optimization, and Part II Expansion. Part II is separated into two stages.

(Apex) Bezuclastinib in Patients With Advanced Systemic Mastocytosis

A Phase 2 Open-Label, Multicenter Clinical Study of the Safety, Efficacy, Pharmacokinetic, and Pharmacodynamic Profiles of CGT9486 as a Single Agent in Patients With Advanced Systemic Mastocytosis

Incidence of AEs according to CTCAE version 5.0 or higher

Percentage change in plasma concentrations of bezuclastinib

Percentage change in mast cell infiltration in the bone marrow and percentage change in eosinophilia and monocytosis in the blood

0 -10 points (higher values represent worse symptom outcomes)

0 - 7 points (higher values represent better symptom outcomes)

0 - 100 (higher values represent better symptom outcomes)

0 - 252 (higher values represent worse symptom outcomes)

Cogent Biosciences, Inc.

Bezuclastinib will be administered orally, once daily continuously for 28-day cycles

Bezuclastinib Tablets (Formulation A)

Bezuclastinib Tablets (Formulation B)

Placebo will be administered orally, once daily continuously for 28-day cycles

Placebo Tablets

Rachael Easton, MD, PhD

This is a multi-part, randomized, double-blind, placebo-controlled Phase 2 clinical study comparing the safety and efficacy of bezuclastinib (CGT9486) plus best supportive care (BSC) with placebo plus BSC in patients with nonadvanced systemic mastocytosis (NonAdvSM), including indolent systemic mastocytosis and smoldering systemic mastocytosis, whose symptoms are not adequately controlled by BSC. This study will be conducted in three parts. Patients in Parts 1a, 1b and 2 will receive bezuclastinib or placebo, and may roll over onto Part 3 to receive treatment with bezuclastinib.

In Part 1a and 1b of the study, patients with NonAdvSM will be randomly assigned to 1 of 2 dose levels of bezuclastinib plus BSC, or to placebo plus BSC. Upon analysis of the Part 1 data, a dose will be selected for Part 2. In Part 2, patients with NonAdvSM will be randomly assigned to the selected dose of bezuclastinib plus BSC, or to placebo plus BSC.

Patients who complete Part 1 or Part 2 may participate in Part 3 in which all patients will receive bezuclastinib plus BSC.

(Summit) A Study to Evaluate the Efficacy and Safety of CGT9486 Versus Placebo in Patients With Indolent or Smoldering Systemic Mastocytosis

A Multi-Part, Randomized, Double-Blind, Placebo-Controlled Phase 2 Clinical Study of The Safety and Efficacy of CGT9486 in Subjects With Nonadvanced Systemic Mastocytosis

Selection of the recommended dose to be used in subsequent parts of the study.

Mean absolute change in a disease-specific patient reported outcome (PRO)

Scale of 0-100, higher numbers represent more severe impairment to quality of life.

Scale of 0-100, higher numbers represent better symptom outcomes

Response rate based on reduction in disease specific PRO

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase Ib/II Study of PLX 3397 and Eribulin in Patients With Metastatic Breast Cancer	NCT01596751	Metastatic Brea...	PLX3397 Eribulin	18 Years -	University of California, San Francisco
(Apex) Bezuclastinib in Patients With Advanced Systemic Mastocytosis	NCT04996875	Advanced System... SM With an Asso... Mast Cell Leuke... Aggressive Syst...	bezuclastinib	18 Years -	Cogent Biosciences, Inc.
Phase Ib/II Study of PLX 3397 and Eribulin in Patients With Metastatic Breast Cancer	NCT01596751	Metastatic Brea...	PLX3397 Eribulin	18 Years -	University of California, San Francisco
(Summit) A Study to Evaluate the Efficacy and Safety of CGT9486 Versus Placebo in Patients With Indolent or Smoldering Systemic Mastocytosis	NCT05186753	SSM Mastocytosis, I... Mastocytosis, S... Mastocytosis	Bezuclastinib T... Bezuclastinib T... Placebo Tablets	18 Years -	Cogent Biosciences, Inc.

Spots Global Cancer Trial Database for plx

Every month we try and update this database with for plx cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for plx

Every month we try and update this database with for plx cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for plx cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.