Locally Advanced or Metastatic Solid Tumor
Conditions
Keywords
rebastinib, breast cancer, ovarian cancer, mesothelioma
Brief summary
This is an open-label Phase 1b/2 multicenter study of rebastinib (DCC-2036) in combination with carboplatin designed to evaluate the safety, tolerability, and pharmacokinetics (PK) in participants with advanced or metastatic solid tumors.
Interventions
DRUGRebastinib
Administered orally
DRUGCarboplatin
Administered by IV infusion
Sponsors
Deciphera Pharmaceuticals, LLC
Study design
Allocation
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 (Dose Escalation). Histologically confirmed diagnosis of a locally advanced or metastatic solid tumor for which carboplatin is considered appropriate treatment. 3. Part 2 (Dose Expansion) * Previously treated, triple-negative breast cancer. * Recurrent platinum-sensitive ovarian cancer. * Histologically confirmed pleural or peritoneal malignant mesothelioma. 4. ECOG performance status 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 (whichever is shorter) prior to the first dose. 2. Not recovered from prior-treatment toxicities to Grade ≤1 or baseline. 3. Peripheral neuropathy of any etiology \>Grade 1. 4. Concurrent malignancy. 5. Known active 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. 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. Symptomatic venous thrombotic event. 13. Active infection ≥Grade 3. 14. Known HIV or HCV infection only if taking medications excluded per protocol, active 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 2.32 years | Number of participants who experienced serious adverse events (SAE) and adverse events (AE). |
| Objective Response Rate (ORR) (Dose Expansion Phase) | Time from CR or PR to disease progression or death due to any cause (Up to 1.53 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. Disease progression 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 |
|---|---|---|
| Progression-free-survival (PFS) | First Dose of Study Drug to PD or Death due to Any Cause (up to 1.63 years) | Time from first dose of study drug to disease progression (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. Disease progression 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. |
| Overall Survival (OS) | Baseline to death due to any cause (Up to 2.12 years) | Time from baseline C1 D1 to date of death due to any cause. Participants who are still alive or who are lost to follow-up will be censored at the date of last contact. |
| Duration of Response (DOR) | Time from PR or CR to PD or Death due to Any Cause (up to 1.53 years) | Time from first partial response (PR) or complete response (CR) to disease progression (PD) or death due to any cause. Evaluation of radiographic disease assessment 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. Disease progression 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. |
| PK: Area Under the Concentration-time Curve 0-3 Hours (AUC 0-3 Hours) (Part 1) | Part 1: Cycle (C) 1 Day (D) 1, C2 D1 (Cycle = 21 Days) | Measure the AUC 0-3 hours |
| Objective Response Rate (ORR) (Dose Escalation Phase) | Time from CR or PR to disease progression or death due to any cause (Up to 1.53 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. Disease progression 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. |
| Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Rebastinib (Part 1) | Part 1: Cycle (C) 1 Day (D) 1, C2 D1 (Cycle = 21 Days) | Cmax of rebastinib |
| Time to Progression (TTP) | First Dose of Study Drug to PD (Up to 1.63 years) | Time from first dose of study drug to the first documentation of progressive disease (PD). Participants were considered to have progressive disease if they had documented progression based on radiologic assessment according to RECIST v1.1. RECIST v1.1 defined disease progression 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part 1 Cohort 1 Escalation Rebastinib 50 mg + Carboplatin AUC5 Dose escalation with rebastinib 50 mg BID PO in 21-day cycles in combination with carboplatin administered by IV infusion at AUC5 at Day 1 of each 21-day cycle. | 3 |
| Part 1 Cohort 2 Escalation Rebastinib 100 mg + Carboplatin AUC5 Dose escalation with rebastinib 100 mg BID PO in 21-day cycles in combination with carboplatin administered by IV infusion at AUC5 at Day 1 of each 21-day cycle. | 14 |
| Part 1 Cohort 3 Escalation Rebastinib 100 mg + Carboplatin AUC6 Dose escalation with rebastinib 100 mg BID PO in 21-day cycles in combination with carboplatin administered by IV infusion at AUC6 at Day 1 of each 21-day cycle. | 5 |
| Part 2 Cohort 1 Expansion Rebastinib 50 mg + Carboplatin AUC5 Dose expansion in TNBC participants. Rebastinib 50 mg BID PO in 21-day cycles in combination with carboplatin administered by IV infusion at AUC5 at Day 1 of each 21-day cycle. | 9 |
| Part 2 Cohort 1 Expansion Rebastinib 100 mg + Carboplatin AUC5 Dose expansion in TNBC participants. Rebastinib 100 mg BID PO in 21-day cycles in combination with carboplatin administered by IV infusion at AUC5 at Day 1 of each 21-day cycle. | 2 |
| Part 2 Cohort 2 Expansion Rebastinib 50 mg + Carboplatin AUC5 Dose expansion in platinum-sensitive ovarian cancer participants. Rebastinib 50 mg BID PO in 21-day cycles in combination with carboplatin administered by IV infusion at AUC5 at Day 1 of each 21-day cycle. | 18 |
| Part 2 Cohort 2 Expansion Rebastinib 100 mg + Carboplatin AUC5 Dose expansion in platinum-sensitive ovarian cancer participants. Rebastinib 100 mg BID PO in 21-day cycles in combination with carboplatin administered by IV infusion at AUC5 at Day 1 of each 21-day cycle. | 2 |
| Part 2 Cohort 3 Expansion Rebastinib 50 mg + Carboplatin AUC5 Dose expansion in mesothelioma participants. Rebastinib 50 mg BID PO in 21-day cycles in combination with carboplatin administered by IV infusion at AUC5 at Day 1 of each 21-day cycle. | 6 |
| Part 2 Cohort 3 Expansion Rebastinib 100 mg + Carboplatin AUC5 Dose expansion in mesothelioma participants. Rebastinib 100 mg BID PO in 21-day cycles in combination with carboplatin administered by IV infusion at AUC5 at Day 1 of each 21-day cycle. | 11 |
| Total | 70 |
Baseline characteristics
| Characteristic | Total | Part 1 Cohort 2 Escalation Rebastinib 100 mg + Carboplatin AUC5 | Part 1 Cohort 3 Escalation Rebastinib 100 mg + Carboplatin AUC6 | Part 2 Cohort 1 Expansion Rebastinib 50 mg + Carboplatin AUC5 | Part 2 Cohort 1 Expansion Rebastinib 100 mg + Carboplatin AUC5 | Part 1 Cohort 1 Escalation Rebastinib 50 mg + Carboplatin AUC5 | Part 2 Cohort 2 Expansion Rebastinib 50 mg + Carboplatin AUC5 | Part 2 Cohort 2 Expansion Rebastinib 100 mg + Carboplatin AUC5 | Part 2 Cohort 3 Expansion Rebastinib 50 mg + Carboplatin AUC5 | Part 2 Cohort 3 Expansion Rebastinib 100 mg + Carboplatin AUC5 |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 27 Participants | 5 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 9 Participants | 0 Participants | 4 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 43 Participants | 9 Participants | 4 Participants | 7 Participants | 2 Participants | 3 Participants | 9 Participants | 2 Participants | 2 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 61 Participants | 11 Participants | 5 Participants | 9 Participants | 1 Participants | 1 Participants | 18 Participants | 2 Participants | 6 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 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 |
| 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 |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 65 Participants | 13 Participants | 5 Participants | 8 Participants | 1 Participants | 3 Participants | 17 Participants | 2 Participants | 6 Participants | 10 Participants |
| Region of Enrollment United States | 70 participants | 14 participants | 5 participants | 9 participants | 2 participants | 3 participants | 18 participants | 2 participants | 6 participants | 11 participants |
| Sex: Female, Male Female | 53 Participants | 8 Participants | 4 Participants | 9 Participants | 2 Participants | 3 Participants | 18 Participants | 2 Participants | 2 Participants | 5 Participants |
| Sex: Female, Male Male | 17 Participants | 6 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants | 6 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 |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 14 | 1 / 5 | 0 / 9 | 0 / 2 | 0 / 18 | 0 / 2 | 0 / 6 | 3 / 11 |
| other Total, other adverse events | 3 / 3 | 13 / 14 | 5 / 5 | 9 / 9 | 2 / 2 | 18 / 18 | 2 / 2 | 6 / 6 | 11 / 11 |
| serious Total, serious adverse events | 2 / 3 | 4 / 14 | 1 / 5 | 5 / 9 | 0 / 2 | 6 / 18 | 0 / 2 | 2 / 6 | 6 / 11 |
Outcome results
Primary
Number of Participants With Adverse Events
Number of participants who experienced serious adverse events (SAE) and adverse events (AE).
Time frame: Baseline up to 2.32 years
Population: All participants who received any study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1 Cohort 1 Escalation Rebastinib 50 mg + Carboplatin AUC5 | Number of Participants With Adverse Events | Any SAE | 2 Participants |
| Part 1 Cohort 1 Escalation Rebastinib 50 mg + Carboplatin AUC5 | Number of Participants With Adverse Events | Any AE | 3 Participants |
| Part 1 Cohort 2 Escalation Rebastinib 100 mg + Carboplatin AUC5 | Number of Participants With Adverse Events | Any SAE | 4 Participants |
| Part 1 Cohort 2 Escalation Rebastinib 100 mg + Carboplatin AUC5 | Number of Participants With Adverse Events | Any AE | 13 Participants |
| Part 1 Cohort 3 Escalation Rebastinib 100 mg + Carboplatin AUC6 | Number of Participants With Adverse Events | Any SAE | 1 Participants |
| Part 1 Cohort 3 Escalation Rebastinib 100 mg + Carboplatin AUC6 | Number of Participants With Adverse Events | Any AE | 5 Participants |
| Part 2 Cohort 1 Expansion Rebastinib 50 mg + Carboplatin AUC5 | Number of Participants With Adverse Events | Any SAE | 5 Participants |
| Part 2 Cohort 1 Expansion Rebastinib 50 mg + Carboplatin AUC5 | Number of Participants With Adverse Events | Any AE | 9 Participants |
| Part 2 Cohort 1 Expansion Rebastinib 100 mg + Carboplatin AUC5 | Number of Participants With Adverse Events | Any SAE | 0 Participants |
| Part 2 Cohort 1 Expansion Rebastinib 100 mg + Carboplatin AUC5 | Number of Participants With Adverse Events | Any AE | 2 Participants |
| Part 2 Cohort 2 Expansion Rebastinib 50 mg + Carboplatin AUC5 | Number of Participants With Adverse Events | Any AE | 18 Participants |
| Part 2 Cohort 2 Expansion Rebastinib 50 mg + Carboplatin AUC5 | Number of Participants With Adverse Events | Any SAE | 6 Participants |
| Part 2 Cohort 2 Expansion Rebastinib 100 mg + Carboplatin AUC5 | Number of Participants With Adverse Events | Any AE | 2 Participants |
| Part 2 Cohort 2 Expansion Rebastinib 100 mg + Carboplatin AUC5 | Number of Participants With Adverse Events | Any SAE | 0 Participants |
| Part 2 Cohort 3 Expansion Rebastinib 50 mg + Carboplatin AUC5 | Number of Participants With Adverse Events | Any SAE | 2 Participants |
| Part 2 Cohort 3 Expansion Rebastinib 50 mg + Carboplatin AUC5 | Number of Participants With Adverse Events | Any AE | 6 Participants |
| Part 2 Cohort 3 Expansion Rebastinib 100 mg + Carboplatin AUC5 | Number of Participants With Adverse Events | Any SAE | 6 Participants |
| Part 2 Cohort 3 Expansion Rebastinib 100 mg + Carboplatin AUC5 | Number of Participants With Adverse Events | Any AE | 11 Participants |
Primary
Objective Response Rate (ORR) (Dose Expansion Phase)
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. Disease progression 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: Time from CR or PR to disease progression or death due to any cause (Up to 1.53 years)
Population: Expansion Phase mITT participants that were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1 Cohort 1 Escalation Rebastinib 50 mg + Carboplatin AUC5 | Objective Response Rate (ORR) (Dose Expansion Phase) | 0 percentage of participants |
| Part 1 Cohort 2 Escalation Rebastinib 100 mg + Carboplatin AUC5 | Objective Response Rate (ORR) (Dose Expansion Phase) | 0 percentage of participants |
| Part 1 Cohort 3 Escalation Rebastinib 100 mg + Carboplatin AUC6 | Objective Response Rate (ORR) (Dose Expansion Phase) | 16.7 percentage of participants |
| Part 2 Cohort 1 Expansion Rebastinib 50 mg + Carboplatin AUC5 | Objective Response Rate (ORR) (Dose Expansion Phase) | 100 percentage of participants |
| Part 2 Cohort 1 Expansion Rebastinib 100 mg + Carboplatin AUC5 | Objective Response Rate (ORR) (Dose Expansion Phase) | 0 percentage of participants |
| Part 2 Cohort 2 Expansion Rebastinib 50 mg + Carboplatin AUC5 | Objective Response Rate (ORR) (Dose Expansion Phase) | 0 percentage of participants |
Secondary
Duration of Response (DOR)
Time from first partial response (PR) or complete response (CR) to disease progression (PD) or death due to any cause. Evaluation of radiographic disease assessment 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. Disease progression 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: Time from PR or CR to PD or Death due to Any Cause (up to 1.53 years)
Population: mITT participants that had CR or PR and were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 2 Cohort 2 Expansion Rebastinib 50 mg + Carboplatin AUC5 | Duration of Response (DOR) | 11.8 months |
| Part 2 Cohort 2 Expansion Rebastinib 100 mg + Carboplatin AUC5 | Duration of Response (DOR) | 13.5 months |
Secondary
Objective Response Rate (ORR) (Dose Escalation Phase)
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. Disease progression 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: Time from CR or PR to disease progression or death due to any cause (Up to 1.53 years)
Population: Escalation Phase mITT participants that were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1 Cohort 1 Escalation Rebastinib 50 mg + Carboplatin AUC5 | Objective Response Rate (ORR) (Dose Escalation Phase) | 0 percentage of participants |
| Part 1 Cohort 2 Escalation Rebastinib 100 mg + Carboplatin AUC5 | Objective Response Rate (ORR) (Dose Escalation Phase) | 0 percentage of participants |
| Part 1 Cohort 3 Escalation Rebastinib 100 mg + Carboplatin AUC6 | Objective Response Rate (ORR) (Dose Escalation Phase) | 0 percentage of participants |
Secondary
Overall Survival (OS)
Time from baseline C1 D1 to date of death due to any cause. Participants who are still alive or who are lost to follow-up will be censored at the date of last contact.
Time frame: Baseline to death due to any cause (Up to 2.12 years)
Population: mITT participants that were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1 Cohort 1 Escalation Rebastinib 50 mg + Carboplatin AUC5 | Overall Survival (OS) | NA months |
| Part 1 Cohort 2 Escalation Rebastinib 100 mg + Carboplatin AUC5 | Overall Survival (OS) | NA months |
| Part 1 Cohort 3 Escalation Rebastinib 100 mg + Carboplatin AUC6 | Overall Survival (OS) | NA months |
| Part 2 Cohort 1 Expansion Rebastinib 50 mg + Carboplatin AUC5 | Overall Survival (OS) | NA months |
| Part 2 Cohort 1 Expansion Rebastinib 100 mg + Carboplatin AUC5 | Overall Survival (OS) | NA months |
| Part 2 Cohort 2 Expansion Rebastinib 50 mg + Carboplatin AUC5 | Overall Survival (OS) | NA months |
| Part 2 Cohort 2 Expansion Rebastinib 100 mg + Carboplatin AUC5 | Overall Survival (OS) | NA months |
| Part 2 Cohort 3 Expansion Rebastinib 50 mg + Carboplatin AUC5 | Overall Survival (OS) | NA months |
| Part 2 Cohort 3 Expansion Rebastinib 100 mg + Carboplatin AUC5 | Overall Survival (OS) | 9.9 months |
Secondary
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Rebastinib (Part 1)
Cmax of rebastinib
Time frame: Part 1: Cycle (C) 1 Day (D) 1, C2 D1 (Cycle = 21 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 Cohort 1 Escalation Rebastinib 50 mg + Carboplatin AUC5 | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Rebastinib (Part 1) | C1 D1 | 92.2 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 157 |
| Part 1 Cohort 1 Escalation Rebastinib 50 mg + Carboplatin AUC5 | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Rebastinib (Part 1) | C2 D1 | 190 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 106 |
| Part 1 Cohort 2 Escalation Rebastinib 100 mg + Carboplatin AUC5 | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Rebastinib (Part 1) | C1 D1 | 120 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 106 |
| Part 1 Cohort 2 Escalation Rebastinib 100 mg + Carboplatin AUC5 | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Rebastinib (Part 1) | C2 D1 | 151 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 67.8 |
| Part 1 Cohort 3 Escalation Rebastinib 100 mg + Carboplatin AUC6 | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Rebastinib (Part 1) | C1 D1 | 144 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 103 |
| Part 1 Cohort 3 Escalation Rebastinib 100 mg + Carboplatin AUC6 | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Rebastinib (Part 1) | C2 D1 | 323 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 18.2 |
Secondary
PK: Area Under the Concentration-time Curve 0-3 Hours (AUC 0-3 Hours) (Part 1)
Measure the AUC 0-3 hours
Time frame: Part 1: Cycle (C) 1 Day (D) 1, C2 D1 (Cycle = 21 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 Cohort 1 Escalation Rebastinib 50 mg + Carboplatin AUC5 | PK: Area Under the Concentration-time Curve 0-3 Hours (AUC 0-3 Hours) (Part 1) | C1 D1 | 186 Nanograms hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 153 |
| Part 1 Cohort 1 Escalation Rebastinib 50 mg + Carboplatin AUC5 | PK: Area Under the Concentration-time Curve 0-3 Hours (AUC 0-3 Hours) (Part 1) | C2 D1 | 380 Nanograms hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 88.3 |
| Part 1 Cohort 2 Escalation Rebastinib 100 mg + Carboplatin AUC5 | PK: Area Under the Concentration-time Curve 0-3 Hours (AUC 0-3 Hours) (Part 1) | C1 D1 | 150 Nanograms hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 125 |
| Part 1 Cohort 2 Escalation Rebastinib 100 mg + Carboplatin AUC5 | PK: Area Under the Concentration-time Curve 0-3 Hours (AUC 0-3 Hours) (Part 1) | C2 D1 | 262 Nanograms hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 103 |
| Part 1 Cohort 3 Escalation Rebastinib 100 mg + Carboplatin AUC6 | PK: Area Under the Concentration-time Curve 0-3 Hours (AUC 0-3 Hours) (Part 1) | C1 D1 | 230 Nanograms hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 116 |
| Part 1 Cohort 3 Escalation Rebastinib 100 mg + Carboplatin AUC6 | PK: Area Under the Concentration-time Curve 0-3 Hours (AUC 0-3 Hours) (Part 1) | C2 D1 | 369 Nanograms hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 98.7 |
Secondary
Progression-free-survival (PFS)
Time from first dose of study drug to disease progression (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. Disease progression 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.
Time frame: First Dose of Study Drug to PD or Death due to Any Cause (up to 1.63 years)
Population: mITT participants that were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1 Cohort 1 Escalation Rebastinib 50 mg + Carboplatin AUC5 | Progression-free-survival (PFS) | 1.4 months |
| Part 1 Cohort 2 Escalation Rebastinib 100 mg + Carboplatin AUC5 | Progression-free-survival (PFS) | 4.0 months |
| Part 1 Cohort 3 Escalation Rebastinib 100 mg + Carboplatin AUC6 | Progression-free-survival (PFS) | 2.3 months |
| Part 2 Cohort 1 Expansion Rebastinib 50 mg + Carboplatin AUC5 | Progression-free-survival (PFS) | 1.5 months |
| Part 2 Cohort 1 Expansion Rebastinib 100 mg + Carboplatin AUC5 | Progression-free-survival (PFS) | 1.3 months |
| Part 2 Cohort 2 Expansion Rebastinib 50 mg + Carboplatin AUC5 | Progression-free-survival (PFS) | 6.7 months |
| Part 2 Cohort 2 Expansion Rebastinib 100 mg + Carboplatin AUC5 | Progression-free-survival (PFS) | 14.6 months |
| Part 2 Cohort 3 Expansion Rebastinib 50 mg + Carboplatin AUC5 | Progression-free-survival (PFS) | NA months |
| Part 2 Cohort 3 Expansion Rebastinib 100 mg + Carboplatin AUC5 | Progression-free-survival (PFS) | 4.8 months |
Secondary
Time to Progression (TTP)
Time from first dose of study drug to the first documentation of progressive disease (PD). Participants were considered to have progressive disease if they had documented progression based on radiologic assessment according to RECIST v1.1. RECIST v1.1 defined disease progression 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.
Time frame: First Dose of Study Drug to PD (Up to 1.63 years)
Population: mITT participants that were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1 Cohort 1 Escalation Rebastinib 50 mg + Carboplatin AUC5 | Time to Progression (TTP) | 1.4 months |
| Part 1 Cohort 2 Escalation Rebastinib 100 mg + Carboplatin AUC5 | Time to Progression (TTP) | 4.0 months |
| Part 1 Cohort 3 Escalation Rebastinib 100 mg + Carboplatin AUC6 | Time to Progression (TTP) | 2.3 months |
| Part 2 Cohort 1 Expansion Rebastinib 50 mg + Carboplatin AUC5 | Time to Progression (TTP) | 1.5 months |
| Part 2 Cohort 1 Expansion Rebastinib 100 mg + Carboplatin AUC5 | Time to Progression (TTP) | 1.3 months |
| Part 2 Cohort 2 Expansion Rebastinib 50 mg + Carboplatin AUC5 | Time to Progression (TTP) | 6.7 months |
| Part 2 Cohort 2 Expansion Rebastinib 100 mg + Carboplatin AUC5 | Time to Progression (TTP) | 14.6 months |
| Part 2 Cohort 3 Expansion Rebastinib 50 mg + Carboplatin AUC5 | Time to Progression (TTP) | NA months |
| Part 2 Cohort 3 Expansion Rebastinib 100 mg + Carboplatin AUC5 | Time to Progression (TTP) | 4.9 months |