Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

Open-label, sequential PLX3397 single-agent dose escalation in combination with paclitaxel in approximately 30 patients with advanced solid tumors. Enrollment completed.

(Closed to recruitment)

Extension cohort at the RP2D of single-agent PLX3397 in combination with paclitaxel in approximately 30 patients in advanced solid tumors. Enrollment completed.

(Closed to recruitment)

Extension cohort at the RP2D of single-agent PLX3397 in combination with paclitaxel in approximately 30 patients with advanced, metastatic, or non-resectable, platinum-resistant or -refractory epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer.

(Closed to recruitment)

PLX3397

This was a 3-part study designed to explore the safety and tolerability of escalating doses of PLX3397 with weekly paclitaxel to establish a recommended Phase 2 dose (RP2D), to confirm RP2D in participants with advanced non-resectable solid tumors, and to determine the efficacy of PLX3397 600 mg twice daily (BID) administered in combination with weekly paclitaxel in participants with advanced, metastatic or non-resectable, platinum-resistant or -refractory epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer.

Safety Study of PLX3397 and Paclitaxel in Patients With Advanced Solid Tumors

A Phase 1b Study to Assess the Safety of PLX3397 and Paclitaxel in Patients With Advanced Solid Tumors

De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

Treatment-emergent adverse events (TEAEs) reported by \>10% of all participants in Parts 1 and 2 are reported.

Treatment-emergent adverse events (TEAEs) reported by \>10% of all participants in Part 3 are reported.

Best overall tumor response (complete response \[CR\], partial response \[PR\], stable disease \[SD\], progressive disease \[PD\]) is reported, including participants who were not evaluable (NE). RECIST v1.1 for target lesions are assessed by magnetic resonance imaging, computed tomography, or positron emission tomography-computed tomography and are summarized as: CR, Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 mm; PR, At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; PD, at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (includes the baseline sum). In addition, the sum must also demonstrate an absolute increase of at least 5 mm; SD, Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

Progression-free survival (PFS) is defined as the number of days from the start of therapy (i.e. Cycle 1 Day 1) to the date of first documented disease progression/relapse or death, whichever occurs first. If the disease progression/relapse does not occur, PFS will be censored as of the date of their last evaluable tumor assessments.

Plexxikon

Daiichi Sankyo

All-cause mortality is reported for all patients enrolled in the study. Serious and other (not including serious) adverse events are reported for the Safety Population.

Participants with advanced solid tumors who received PLX3397 600 mg/day.

Part 1: Cohort 1; 600 mg/Day

Participants with advanced solid tumors who received PLX3397 800 mg/day.

Part 1: Cohort 2; 800 mg/Day

Participants with advanced solid tumors who received PLX3397 1000 mg/day.

Part 1: Cohort 3; 1000 mg/Day

Participants with advanced solid tumors who received PLX3397 1200 mg/day.

Part 1: Cohort 4; 1200 mg/Day

Participants with advanced solid tumors who received PLX3397 1600 mg/day.

Part 1 and 2: Cohort 5; 1600 mg/Day

All participants with advanced solid tumors who received PLX3397 600 mg BID as lead-in treatment.

Part 3: PLX3397 600 mg BID

All participants with advanced solid tumors who received paclitaxel 80 mg/m\^2 intravenous weekly as lead-in treatment.

Part 3: Paclitaxel 80 mg/m^2

All participants who received PLX3397 600 mg BID + paclitaxel 80 mg/m\^2 intravenous weekly as lead-in treatment.

Part 3: PLX3397 600 mg BID + Paclitaxel 80 mg/m^2

All participants with advanced solid tumors who received PLX3397 600 mg BID as Cycle 1 lead-in treatment. After Cycle 1, participants were treated with PLX3397 600 mg BID and paclitaxel 80 mg/m\^2 IV weekly.

All participants with advanced solid tumors who received paclitaxel 80 mg/m\^2 intravenous weekly as Cycle 1 lead-in treatment. After Cycle 1, participants were treated with PLX3397 600 mg BID and paclitaxel 80 mg/m\^2 IV weekly.

All participants who received PLX3397 600 mg BID + paclitaxel 80 mg/m\^2 intravenous weekly as Cycle 1 lead-in treatment.

Part 3: PLX3397 600 mg + Paclitaxel 80 mg/m^2

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

The baseline analysis population included all participants who were treated and included in the Safety Population (n=72).

Medical Director

Any TEAE

Gastrointestinal disorders

Nausea

Diarrhea

Vomiting

Constipation

General disorders/administrative site conditions

Fatigue

Edema peripheral

Pyrexia

Blood and lymphatic disorders

Anemia

Neutropenia

Metabolism and nutrition disorders

Decreased appetite

Hypokalemia

Hypophosphatemia

Skin and subcutaneous disorders

Alopecia

Rash

Pruritus

Respiratory, thoracic, and mediastinal disorders

Dyspnea

Cough

Investigations

Aspartate aminotransferase increased

Lymphocyte count decreased

White blood cell count decreased

Blood creatinine phosphokinase increased

Neutrohil count decreased

Alanine aminotransferase increased

Blood alkaline phosphatase increased

Respiratory rate increased

Weight decreased

Nervous system disorders

Dysgeusia

Dizziness

Neuropathy peripheral

Headache

Vascular disorders

Hypertension

Eye disorders

Periorbital edema

Vision blurred

Psychiatric disorders

Insomnia

Safety events were assessed in the Safety Population.

Percentage of Participants With Treatment-emergent Adverse Events (>10%) Classified by Preferred Term Following PLX3397 Administered in Combination With Paclitaxel (Parts 1 and 2) (Safety Population)

Abdominal distension

Abdominal pain

Stomatitis

Colitis

Toothache

Chills

Chest pain

Face edema

Skin and subcutaneous tissue disorders

Epistaxis

Oropharyngeal pain

Musculoskeletal and connective tissue disorders

Pain in extremity

Myalgia

Blood bilirubin increased

Neutrophil count decreased

Blood and lymphatic system disorders

Infections and infestations

Pneumonia

Renal and urinary disorders

Dysuria

Urinary incontinence

Injury, poisoning, and procedural complications

Contusion

Reproductive system and breast disorders

Vaginal hemorrhage

Percentage of Participants With TEAEs (>10%) Classified by Preferred Term Following PLX3397 Administered in Combination With Paclitaxel (Part 3) (Safety Population)

Complete response (CR)

Partial response (PR)

Stable disease

Progressive disease

Unable to assess

Best overall response rate (CR or PR)

Clinical benefit rate (CR, PR, or stable disease)

Best overall tumor response was assessed in the Efficacy Evaluable Population.

Best Overall Tumor Response Based on RECIST V1.1 Following PLX3397 Administered in Combination With Paclitaxel (Parts 1 and 2) (Efficacy Evaluable Population)

Stable disease (SD)

Progressive disease (PD)

Best Overall Tumor Response Based on RECIST V1.1 Following PLX3397 Administered in Combination With Paclitaxel (Part 3) (Efficacy Evaluable Population)

Duration of response was assessed in the Efficacy Evaluable Population.

Duration of Response Following PLX3397 Administered in Combination With Paclitaxel (Parts 1 and 2) (Efficacy Evaluable Population)

Duration of response based on patients with CR or PR was assessed in the Efficacy Evaluable Population.

Duration of Response Following PLX3397 Administered in Combination With Paclitaxel (Part 3) (Efficacy Evaluable Population)

Progression-free survival was assessed in the Efficacy Evaluable Population.

Progression-free Survival Following PLX3397 Administered in Combination With Paclitaxel (Part 3) (Efficacy Evaluable Population)

Participants with advanced solid tumors who received PLX3397 600 mg BID administered as three 100-mg capsules in the morning and evening, or two 200-mg capsules in the morning and one 200-mg capsule in the evening.

Part 1: 600 mg BID

Participants with advanced solid tumors who received PLX3397 800 mg administered 400 mg BID.

Part 1: 800 mg (400 mg BID)

Participants with advanced solid tumors who received PLX3397 1000 mg BID administered as five 100-mg capsules in the morning and evening, or three 200-mg capsules in the morning and two 200-mg capsules in the evening.

Part 1: 1000 mg (BID)

Participants with advanced solid tumors who received PLX3397 1200 mg administered 600 mg BID.

Part 1: 1200 mg (600 mg BID)

Participants with advanced solid tumors who received PLX3397 1600 mg administered 800 mg BID.

Part 1 and 2: 1600 mg (800 mg BID)

Part 3: 1200 mg (600 mg BID)

Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.

A Summary of Pharmacokinetic Parameter (Tmax) Following Exposure to PLX3397 (Parts 1 and 3)

A Summary of Pharmacokinetic Parameter (Cmax) Following Exposure to PLX3397 (Parts 1 and 3)

AUC (0-4)

AUC (0-6)

AUC (0-12)

Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set, except for AUC(0-6) which was not performed for Part 1 and 2 participants, only participants in Part 3.

A Summary of Pharmacokinetic Parameters (AUC[0-4h], AUC[0-6h], and AUC[0-12h]) Following Exposure to PLX3397 (Parts 1 and 3)

Any Paclitaxel-related TEAE

Safety events were assessed in the Safety Analysis Set.

Percentage of Participants With PLX3397-Related Treatment-emergent Adverse Events (>10%) by Preferred Term (Parts 1 and 2) (Safety Analysis Set)

Percentage of Participants With Paclitaxel-Related Treatment-emergent Adverse Events (>10%) by Preferred Term (Parts 1 and 2) (Safety Analysis Set)

Any related TEAE

Percentage of Participants With PLX3397- and/or Paclitaxel-Related TEAEs (>10%) by Preferred Term (Part 3) (Safety Analysis Set)

All participants with advanced solid tumors who received PLX3397 600 mg twice daily (BID) as Cycle 1 lead-in treatment. After Cycle 1, participants were treated with PLX3397 600 mg BID and paclitaxel 80 mg/m\^2 IV weekly.

All participants with advanced solid tumors who received paclitaxel 80 mg/m\^2 intravenous weekly as Cycle 1 lead-in treatment. After Cycle 1, participants were treated with PLX3397 600 mg twice daily (BID) and paclitaxel 80 mg/m\^2 IV weekly.

All participants who received PLX3397 600 mg twice daily (BID) + paclitaxel 80 mg/m\^2 intravenous weekly as Cycle 1 lead-in treatment.

Spots Global Cancer Trial Database for Safety Study of PLX3397 and Paclitaxel in Patients With Advanced Solid Tumors

Trial Identification

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Study Description

Keywords

Eligibility

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