Locally Advanced or Metastatic Solid Tumor
Conditions
Keywords
rebastinib, paclitaxel, breast cancer, ovarian cancer, endometrial cancer, gynecological carcinosarcoma, malignant mixed Mullerian tumor (MMMT)
Brief summary
This is an open-label Phase 1b/2 multicenter study of rebastinib (DCC-2036) in combination with paclitaxel designed to evaluate the safety, tolerability, and pharmacokinetics (PK) in patients with advanced or metastatic solid tumors.
Interventions
DRUGRebastinib
Administered orally
DRUGPaclitaxel
Paclitaxel administered by IV infusion at 80 mg/m\^2
Sponsors
Deciphera Pharmaceuticals, LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female patients ≥18 years of age at the time of informed consent 2. Part 1 Histologically confirmed diagnosis of a locally advanced or metastatic solid tumor for which paclitaxel is considered appropriate treatment 3. Part 2 * Triple-negative and Stage IV inflammatory breast cancer * Recurrent ovarian cancer * Recurrent, metastatic or high-risk endometrial cancer * Advanced (stage III or IV), or recurrent gynecological carcinosarcoma * Homologous or heterologous type carcinosarcoma (malignant mixed Mullerian tumor \[MMMT\] allowed 4. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of ≤2 5. Able to provide an archival tumor tissue sample 6. Adequate organ function and bone marrow reserve 7. If a female of childbearing potential, must have a negative pregnancy test prior to enrollment 8. Patient must provide signed consent to participate in the study and is willing to comply with study-specific procedures
Exclusion criteria
1. Received prior anticancer or other investigational therapy within 28 days or 5× the half-life prior to the first dose 2. Not recovered from prior-treatment toxicities to Grade ≤1 3. Peripheral neuropathy of any etiology \>Grade 1 4. Concurrent malignancy 5. Known active central nervous system (CNS) metastases 6. Use of systemic corticosteroids 7. Known retinal neovascularization, macular edema or macular degeneration 8. History or presence of clinically relevant cardiovascular abnormalities 9. QT interval corrected by Fridericia's formula (QTcF) \>450 ms in males or \>470 ms in females 10. Left ventricular ejection fraction (LVEF) \<50% at screening 11. Arterial thrombotic or embolic events 12. Venous thrombotic event 13. Active infection ≥Grade 3 14. Human immunodeficiency virus (HIV) or hepatitis C (HCV) infection only if taking medications excluded per protocol, active hepatitis B (HBV), or active HCV infection 15. Use of proton pump inhibitors 16. If female, the patient is pregnant or lactating 17. Major surgery 4 weeks prior to the first dose of study drug 18. Malabsorption syndrome or other illness which could affect oral absorption 19. Known allergy or hypersensitivity to any component of rebastinib or any of its excipients. 20. Any other clinically significant comorbidities
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | Baseline up to 2.89 years | Number of participants (pts) who experienced serious adverse events (SAE) and adverse events (AE). |
| Objective Response Rate (ORR) (Part 2 Expansion) | Baseline to PD or Death due to Any Cause (Up to 1.54 years) | Percentage of participants who achieved an objective response of Complete Response (CR) or Partial Response (PR) per Response Evaluation Criteria in Solid Tumor (RECIST) v1.1. CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to \<10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline, or the appearance of one or more new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Progression (TTP) | First Dose of Study Drug to PD (Up to 2.61 years) | Time from first dose of study drug to the earliest documented evidence of PD. Per RECIST v1.1, PD defined as at least a 20% increase in the sum of the disease measurements for measurable lesions, taking as reference the smallest disease measurement recorded since the start of treatment, or the appearance of one or more new lesions. mRECIST used for pleural mesothelioma defines PD as an increase of at least 20% in the sum of the diameters of viable target lesions. |
| Progression-free-survival (PFS) | First Dose of Study Drug to PD or Death due to Any Cause (Up to 2.61 years) | Time from first dose of study drug to the earliest documented evidence of PD or death due to any cause. Participants who undergo surgical resection of target or non-target lesions, who have received other anticancer treatments, including surgical resection or radiation (other than palliative radiation to pre-existing bone metastases'), or who do not have a documented date of progression or death due to any cause will be censored at the date of the last assessment. PD per RECIST v1.1 is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline; or the appearance of one or more new lesions. mRECIST used for pleural mesothelioma defines PD as an increase of at least 20% in the sum of the diameters of viable target lesions. |
| Objective Response Rate (ORR) (Part 1 Escalation) | Baseline to PD or Death due to Any Cause (Up to 0.92 years) | Percentage of pts who achieved an objective response of Complete Response (CR) or Partial Response (PR). Per RECIST v1.1, CR defined as disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to have reduction in short axis to \<10 mm. PR defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, or the appearance of one or more new lesions. Modified RECIST (mRECIST) used for pleural mesothelioma defines CR as the disappearance of any intratumoural arterial enhancement in all target lesions; PR as at least a 30% decrease in the sum of diameters of viable target lesions, taking as reference the baseline sum of the diameters of target lesions; PD as an increase of at least 20% in the sum of the diameters of viable target les |
| Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Rebastinib (Part 1) | Part 1: Cycle 1 Day 1 (C1 D1), C1 D15 (Cycle = 28 days) | Measure the Cmax |
| PK: Area Under the Concentration-time Curve (AUC) 0-6 Hours of Rebastinib (Part 1) | Part 1: Cycle 1 Day 1 (C1 D1), C1 D15 (Cycle = 28 days) | Measure the AUC 0-6 hours |
| Overall Survival (OS) | First Dose of Study Drug to Death due to Any Cause (Up to 2.82 years) | Time from first dose of study drug to date of death due to any cause. Participants who were still alive or who were lost to follow-up will be censored at the date of last contact. |
| Duration of Response (DOR) | Time from CR or PR to PD or Death due to Any Cause (Up to 1.54 years) | Time from CR or PR to the earliest documented evidence of PD or death due to any cause. Per RECIST v1.1, CR defined as disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to have reduction in short axis to \<10 mm. PR defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, or the appearance of one or more new lesions. mRECIST used for pleural mesothelioma defines CR as the disappearance of any intratumoural arterial enhancement in all target lesions; PR as at least a 30% decrease in the sum of diameters of viable target lesions, taking as reference the baseline sum of the diameters of target lesions; PD as an increase of at least 20% in the sum of the diameters of viable target lesions. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part 1 Arm 1 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 Dose escalation of rebastinib 50 mg BID PO in combination with paclitaxel administered by IV infusion at 80 mg/m\^2 on days 1, 8, and 15 of repeated 28-day cycles. | 24 |
| Part 1 Arm 2 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 Dose escalation of rebastinib 100 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 of repeated 28-day cycles. | 19 |
| Part 2 Cohort 1 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 Dose expansion in TNBC. Rebastinib 50 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 of repeated 28-day cycles. | 12 |
| Part 2 Cohort 1 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 Dose expansion in TNBC. Rebastinib 100 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 of repeated 28-day cycles. | 6 |
| Part 2 Cohort 2 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 Dose expansion in inflammatory breast cancer. Rebastinib 50 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 of repeated 28-day cycles. | 15 |
| Part 2 Cohort 2 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 Dose expansion in inflammatory breast cancer. Rebastinib 100 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 of repeated 28-day cycles. | 5 |
| Part 2 Cohort 3 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 Dose expansion in ovarian cancer. Rebastinib 50 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 of repeated 28-day cycles. | 28 |
| Part 2 Cohort 3 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 Dose expansion in ovarian cancer. Rebastinib 100 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 of repeated 28-day cycles. | 10 |
| Part 2 Cohort 4 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 Dose expansion in endometrial cancer. Rebastinib 50 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 of repeated 28-day cycles. | 22 |
| Part 2 Cohort 4 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 Dose expansion in endometrial cancer. Rebastinib 100 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 of repeated 28-day cycles. | 16 |
| Part 2 Cohort 5 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 Dose expansion in gynecological carcinosarcoma (GCS). Rebastinib 50 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 of repeated 28-day cycles. | 20 |
| Total | 177 |
Baseline characteristics
| Characteristic | Total | Part 1 Arm 2 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 | Part 2 Cohort 1 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | Part 1 Arm 1 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | Part 2 Cohort 1 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 | Part 2 Cohort 2 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | Part 2 Cohort 2 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 | Part 2 Cohort 3 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | Part 2 Cohort 3 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 | Part 2 Cohort 4 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | Part 2 Cohort 4 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 | Part 2 Cohort 5 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 71 Participants | 5 Participants | 5 Participants | 6 Participants | 2 Participants | 1 Participants | 1 Participants | 13 Participants | 2 Participants | 15 Participants | 7 Participants | 14 Participants |
| Age, Categorical Between 18 and 65 years | 106 Participants | 14 Participants | 7 Participants | 18 Participants | 4 Participants | 14 Participants | 4 Participants | 15 Participants | 8 Participants | 7 Participants | 9 Participants | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 26 Participants | 2 Participants | 1 Participants | 5 Participants | 1 Participants | 2 Participants | 0 Participants | 4 Participants | 0 Participants | 3 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 9 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 136 Participants | 15 Participants | 11 Participants | 19 Participants | 4 Participants | 11 Participants | 5 Participants | 20 Participants | 9 Participants | 16 Participants | 13 Participants | 13 Participants |
| Region of Enrollment United States | 177 participants | 19 participants | 12 participants | 24 participants | 6 participants | 15 participants | 5 participants | 28 participants | 10 participants | 22 participants | 16 participants | 20 participants |
| Sex: Female, Male Female | 168 Participants | 15 Participants | 12 Participants | 19 Participants | 6 Participants | 15 Participants | 5 Participants | 28 Participants | 10 Participants | 22 Participants | 16 Participants | 20 Participants |
| Sex: Female, Male Male | 9 Participants | 4 Participants | 0 Participants | 5 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 7 / 24 | 4 / 19 | 0 / 12 | 1 / 6 | 1 / 15 | 0 / 5 | 0 / 28 | 2 / 10 | 2 / 22 | 0 / 16 | 3 / 20 |
| other Total, other adverse events | 23 / 24 | 15 / 19 | 12 / 12 | 6 / 6 | 15 / 15 | 5 / 5 | 28 / 28 | 10 / 10 | 22 / 22 | 16 / 16 | 20 / 20 |
| serious Total, serious adverse events | 16 / 24 | 12 / 19 | 3 / 12 | 3 / 6 | 2 / 15 | 3 / 5 | 9 / 28 | 5 / 10 | 10 / 22 | 9 / 16 | 9 / 20 |
Outcome results
Primary
Number of Participants With Adverse Events
Number of participants (pts) who experienced serious adverse events (SAE) and adverse events (AE).
Time frame: Baseline up to 2.89 years
Population: All participants who received any study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1 Arm 1 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | Number of Participants With Adverse Events | Any AE | 24 Participants |
| Part 1 Arm 1 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | Number of Participants With Adverse Events | Any SAE | 16 Participants |
| Part 1 Arm 2 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 | Number of Participants With Adverse Events | Any SAE | 12 Participants |
| Part 1 Arm 2 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 | Number of Participants With Adverse Events | Any AE | 18 Participants |
| Part 2 Cohort 1 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | Number of Participants With Adverse Events | Any AE | 12 Participants |
| Part 2 Cohort 1 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | Number of Participants With Adverse Events | Any SAE | 3 Participants |
| Part 2 Cohort 1 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 | Number of Participants With Adverse Events | Any SAE | 3 Participants |
| Part 2 Cohort 1 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 | Number of Participants With Adverse Events | Any AE | 6 Participants |
| Part 2 Cohort 2 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | Number of Participants With Adverse Events | Any AE | 15 Participants |
| Part 2 Cohort 2 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | Number of Participants With Adverse Events | Any SAE | 2 Participants |
| Part 2 Cohort 2 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 | Number of Participants With Adverse Events | Any AE | 5 Participants |
| Part 2 Cohort 2 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 | Number of Participants With Adverse Events | Any SAE | 3 Participants |
| Part 2 Cohort 3 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | Number of Participants With Adverse Events | Any AE | 28 Participants |
| Part 2 Cohort 3 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | Number of Participants With Adverse Events | Any SAE | 9 Participants |
| Part 2 Cohort 3 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 | Number of Participants With Adverse Events | Any SAE | 5 Participants |
| Part 2 Cohort 3 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 | Number of Participants With Adverse Events | Any AE | 10 Participants |
| Part 2 Cohort 4 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | Number of Participants With Adverse Events | Any AE | 22 Participants |
| Part 2 Cohort 4 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | Number of Participants With Adverse Events | Any SAE | 10 Participants |
| Part 2 Cohort 4 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 | Number of Participants With Adverse Events | Any SAE | 9 Participants |
| Part 2 Cohort 4 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 | Number of Participants With Adverse Events | Any AE | 16 Participants |
| Part 2 Cohort 5 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | Number of Participants With Adverse Events | Any SAE | 9 Participants |
| Part 2 Cohort 5 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | Number of Participants With Adverse Events | Any AE | 20 Participants |
Primary
Objective Response Rate (ORR) (Part 2 Expansion)
Percentage of participants who achieved an objective response of Complete Response (CR) or Partial Response (PR) per Response Evaluation Criteria in Solid Tumor (RECIST) v1.1. CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to \<10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline, or the appearance of one or more new lesions.
Time frame: Baseline to PD or Death due to Any Cause (Up to 1.54 years)
Population: Part 2 mITT participants that were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1 Arm 1 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | Objective Response Rate (ORR) (Part 2 Expansion) | 0 percentage of participants |
| Part 1 Arm 2 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 | Objective Response Rate (ORR) (Part 2 Expansion) | 16.7 percentage of participants |
| Part 2 Cohort 1 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | Objective Response Rate (ORR) (Part 2 Expansion) | 7.7 percentage of participants |
| Part 2 Cohort 1 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 | Objective Response Rate (ORR) (Part 2 Expansion) | 25.0 percentage of participants |
| Part 2 Cohort 2 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | Objective Response Rate (ORR) (Part 2 Expansion) | 30.8 percentage of participants |
| Part 2 Cohort 2 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 | Objective Response Rate (ORR) (Part 2 Expansion) | 11.1 percentage of participants |
| Part 2 Cohort 3 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | Objective Response Rate (ORR) (Part 2 Expansion) | 20.0 percentage of participants |
| Part 2 Cohort 3 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 | Objective Response Rate (ORR) (Part 2 Expansion) | 35.7 percentage of participants |
| Part 2 Cohort 4 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | Objective Response Rate (ORR) (Part 2 Expansion) | 5.3 percentage of participants |
Secondary
Duration of Response (DOR)
Time from CR or PR to the earliest documented evidence of PD or death due to any cause. Per RECIST v1.1, CR defined as disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to have reduction in short axis to \<10 mm. PR defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, or the appearance of one or more new lesions. mRECIST used for pleural mesothelioma defines CR as the disappearance of any intratumoural arterial enhancement in all target lesions; PR as at least a 30% decrease in the sum of diameters of viable target lesions, taking as reference the baseline sum of the diameters of target lesions; PD as an increase of at least 20% in the sum of the diameters of viable target lesions.
Time frame: Time from CR or PR to PD or Death due to Any Cause (Up to 1.54 years)
Population: mITT participants that had CR or PR and were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1 Arm 1 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | Duration of Response (DOR) | 11.1 months |
| Part 1 Arm 2 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 | Duration of Response (DOR) | NA months |
| Part 2 Cohort 1 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 | Duration of Response (DOR) | 6.9 months |
| Part 2 Cohort 2 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | Duration of Response (DOR) | 7.4 months |
| Part 2 Cohort 2 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 | Duration of Response (DOR) | NA months |
| Part 2 Cohort 3 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | Duration of Response (DOR) | 6.5 months |
| Part 2 Cohort 3 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 | Duration of Response (DOR) | 5.5 months |
| Part 2 Cohort 4 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | Duration of Response (DOR) | NA months |
| Part 2 Cohort 4 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 | Duration of Response (DOR) | 8.8 months |
| Part 2 Cohort 5 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | Duration of Response (DOR) | NA months |
Secondary
Objective Response Rate (ORR) (Part 1 Escalation)
Percentage of pts who achieved an objective response of Complete Response (CR) or Partial Response (PR). Per RECIST v1.1, CR defined as disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to have reduction in short axis to \<10 mm. PR defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, or the appearance of one or more new lesions. Modified RECIST (mRECIST) used for pleural mesothelioma defines CR as the disappearance of any intratumoural arterial enhancement in all target lesions; PR as at least a 30% decrease in the sum of diameters of viable target lesions, taking as reference the baseline sum of the diameters of target lesions; PD as an increase of at least 20% in the sum of the diameters of viable target les
Time frame: Baseline to PD or Death due to Any Cause (Up to 0.92 years)
Population: Part 1 mITT participants that were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1 Arm 1 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | Objective Response Rate (ORR) (Part 1 Escalation) | 16.7 percentage of participants |
| Part 1 Arm 2 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 | Objective Response Rate (ORR) (Part 1 Escalation) | 21.4 percentage of participants |
Secondary
Overall Survival (OS)
Time from first dose of study drug to date of death due to any cause. Participants who were still alive or who were lost to follow-up will be censored at the date of last contact.
Time frame: First Dose of Study Drug to Death due to Any Cause (Up to 2.82 years)
Population: mITT participants that were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1 Arm 1 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | Overall Survival (OS) | NA months |
| Part 1 Arm 2 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 | Overall Survival (OS) | NA months |
| Part 2 Cohort 1 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | Overall Survival (OS) | NA months |
| Part 2 Cohort 1 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 | Overall Survival (OS) | NA months |
| Part 2 Cohort 2 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | Overall Survival (OS) | NA months |
| Part 2 Cohort 2 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 | Overall Survival (OS) | NA months |
| Part 2 Cohort 3 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | Overall Survival (OS) | NA months |
| Part 2 Cohort 3 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 | Overall Survival (OS) | NA months |
| Part 2 Cohort 4 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | Overall Survival (OS) | NA months |
| Part 2 Cohort 4 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 | Overall Survival (OS) | NA months |
| Part 2 Cohort 5 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | Overall Survival (OS) | NA months |
Secondary
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Rebastinib (Part 1)
Measure the Cmax
Time frame: Part 1: Cycle 1 Day 1 (C1 D1), C1 D15 (Cycle = 28 days)
Population: Part 1 participants who received any study drug and had evaluable Cmax data at each timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 Arm 1 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Rebastinib (Part 1) | Cycle 1 Day 1 | 77.4 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 67.7 |
| Part 1 Arm 1 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Rebastinib (Part 1) | Cycle 1 Day 15 | 89.7 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 80.1 |
| Part 1 Arm 2 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Rebastinib (Part 1) | Cycle 1 Day 1 | 132 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 76.4 |
| Part 1 Arm 2 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Rebastinib (Part 1) | Cycle 1 Day 15 | 143 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 47.6 |
Secondary
PK: Area Under the Concentration-time Curve (AUC) 0-6 Hours of Rebastinib (Part 1)
Measure the AUC 0-6 hours
Time frame: Part 1: Cycle 1 Day 1 (C1 D1), C1 D15 (Cycle = 28 days)
Population: Part 1 participants who received any study drug and had evaluable AUC data at each timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 Arm 1 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | PK: Area Under the Concentration-time Curve (AUC) 0-6 Hours of Rebastinib (Part 1) | Cycle 1 Day 1 | 204 Hour times nanograms per hour (h*ng/mL) | Geometric Coefficient of Variation 67.9 |
| Part 1 Arm 1 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | PK: Area Under the Concentration-time Curve (AUC) 0-6 Hours of Rebastinib (Part 1) | Cycle 1 Day 15 | 283 Hour times nanograms per hour (h*ng/mL) | Geometric Coefficient of Variation 80.8 |
| Part 1 Arm 2 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 | PK: Area Under the Concentration-time Curve (AUC) 0-6 Hours of Rebastinib (Part 1) | Cycle 1 Day 1 | 337 Hour times nanograms per hour (h*ng/mL) | Geometric Coefficient of Variation 83.9 |
| Part 1 Arm 2 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 | PK: Area Under the Concentration-time Curve (AUC) 0-6 Hours of Rebastinib (Part 1) | Cycle 1 Day 15 | 457 Hour times nanograms per hour (h*ng/mL) | Geometric Coefficient of Variation 56.6 |
Secondary
Progression-free-survival (PFS)
Time from first dose of study drug to the earliest documented evidence of PD or death due to any cause. Participants who undergo surgical resection of target or non-target lesions, who have received other anticancer treatments, including surgical resection or radiation (other than palliative radiation to pre-existing bone metastases'), or who do not have a documented date of progression or death due to any cause will be censored at the date of the last assessment. PD per RECIST v1.1 is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline; or the appearance of one or more new lesions. mRECIST used for pleural mesothelioma defines PD as an increase of at least 20% in the sum of the diameters of viable target lesions.
Time frame: First Dose of Study Drug to PD or Death due to Any Cause (Up to 2.61 years)
Population: mITT participants that were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1 Arm 1 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | Progression-free-survival (PFS) | 6.5 months |
| Part 1 Arm 2 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 | Progression-free-survival (PFS) | NA months |
| Part 2 Cohort 1 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | Progression-free-survival (PFS) | 6.4 months |
| Part 2 Cohort 1 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 | Progression-free-survival (PFS) | 5.3 months |
| Part 2 Cohort 2 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | Progression-free-survival (PFS) | 3.7 months |
| Part 2 Cohort 2 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 | Progression-free-survival (PFS) | NA months |
| Part 2 Cohort 3 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | Progression-free-survival (PFS) | 9.1 months |
| Part 2 Cohort 3 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 | Progression-free-survival (PFS) | 7.7 months |
| Part 2 Cohort 4 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | Progression-free-survival (PFS) | 6.2 months |
| Part 2 Cohort 4 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 | Progression-free-survival (PFS) | 9.4 months |
| Part 2 Cohort 5 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | Progression-free-survival (PFS) | 3.5 months |
Secondary
Time to Progression (TTP)
Time from first dose of study drug to the earliest documented evidence of PD. Per RECIST v1.1, PD defined as at least a 20% increase in the sum of the disease measurements for measurable lesions, taking as reference the smallest disease measurement recorded since the start of treatment, or the appearance of one or more new lesions. mRECIST used for pleural mesothelioma defines PD as an increase of at least 20% in the sum of the diameters of viable target lesions.
Time frame: First Dose of Study Drug to PD (Up to 2.61 years)
Population: mITT participants that were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1 Arm 1 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | Time to Progression (TTP) | 14.7 months |
| Part 1 Arm 2 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 | Time to Progression (TTP) | NA months |
| Part 2 Cohort 1 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | Time to Progression (TTP) | 6.4 months |
| Part 2 Cohort 1 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 | Time to Progression (TTP) | 5.3 months |
| Part 2 Cohort 2 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | Time to Progression (TTP) | 3.7 months |
| Part 2 Cohort 2 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 | Time to Progression (TTP) | NA months |
| Part 2 Cohort 3 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | Time to Progression (TTP) | 9.1 months |
| Part 2 Cohort 3 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 | Time to Progression (TTP) | 9.0 months |
| Part 2 Cohort 4 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | Time to Progression (TTP) | 6.2 months |
| Part 2 Cohort 4 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 | Time to Progression (TTP) | 9.4 months |
| Part 2 Cohort 5 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 | Time to Progression (TTP) | 3.5 months |