Cancer of Pancreas, Cancer of the Pancreas, Pancreas Cancer, Pancreatic Cancer
Conditions
Brief summary
In light of the central role of extracellular signal-regulated kinases (ERK) in pancreatic cancer, the investigators propose a phase I study to evaluate the ERK inhibitor BVD-523 at the recommended phase 2 dose in combination with nab-paclitaxel plus gemcitabine in patients with newly diagnosed metastatic pancreatic cancer. The primary endpoint will be maximum tolerated dose (MTD) or RP2D and safety. The secondary endpoints include safety, response rate, biochemical response, progression-free survival (PFS) and overall survival (OS). The exploratory endpoints include the assessing the impact of BVD-523 on the MEK/ERK pathway and other major pathway pertain to pancreatic cancer.
Interventions
Sponsors
BioMed Valley Discoveries, Inc
National Cancer Institute (NCI)
Washington University School of Medicine
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed newly diagnosed treatment-naïve metastatic adenocarcinoma of the pancreas with metastatic disease diagnosed no more than 6 weeks prior to enrollment. Patients with advanced pancreatic cancer progressed on 5-FU (or capecitabine) based regimen will be allowed in the expansion cohort. * Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan or MRI, as ≥ 20 mm by chest x-ray, or ≥ 10 mm with calipers by clinical exam. * At least 18 years of age. * Life expectancy \> 3 months. * ECOG performance status ≤ 1 * Normal bone marrow and organ function as defined below: * Absolute neutrophil count ≥ 1,500/mcL * Platelets ≥ 100,000/mcL * Hemoglobin ≥ 9.0 g/dL * Total bilirubin ≤ IULN * AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN, unless there are liver metastases in which case AST and ALT ≤ 5.0 x IULN * Creatinine ≤ 1.5 x IULN OR GFR of ≥ 50 mL/min * Cardiac function ≥ ILLN, e.g., LVEF of \> 50% as assessed by MUGA or ECHO, QTc \< 470 ms * Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry, for the duration of study participation, and for three months following study discontinuation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. * Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
Exclusion criteria
* Current use or anticipated need for alternative, holistic, naturopathic, or botanical formulations used for the purpose of cancer treatment. * A history of other malignancy with the exception of those treated with curative intent with no evidence of disease for 2 years. * Currently receiving any other investigational agents. * Known brain metastases or CNS involvement. * Significant ascites that require therapeutic paracentesis. * A history of allergic reactions attributed to compounds of similar chemical or biologic composition to BVD-523, gemcitabine, nab-paclitaxel, or other agents used in the study. * Neuropathy ≥ grade 2. * History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR). * History of interstitial lung disease or pneumonitis. * Concurrent therapy with drugs known to be strong inhibitors of CYP1A2, CYP2D6, and CYP3A4, or strong inducers of CYP3A4 (see Appendix B). * Gastrointestinal condition which could impair absorption of BVD-523 or inability to ingest BVD-523. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 7 days of study entry. * Known HIV-positivity.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) of BVD-523 | Completion of cycle 1 for all dose de-escalation patients (1.8 years), the first cycle is 28 days for each individual patient | -The maximum tolerated dose (MTD) is defined as the Dose Level 1 if 0 or 1 dose-limiting toxicities (DLTs) are seen in patients at that dose level or Dose Level -1 if 2+ DLTs are seen in Dose Level 1 but only 0 or 1 DLTs are seen in patients at Dose Level -1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate | Through completion of treatment (median time was 37.5 days) | * Response rate is the percentage of participants with best response of complete response or partial response per RECIST 1.1 * Complete response (CR): disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. * Partial response (PR): at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. |
| Biochemical Response of Treatment Regimen | Through completion of treatment (median time was 37.5 days) | -The biochemical response (BR) is defined as more than 50% of decrease from baseline CA 19-9 |
| Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | 30 days after completion of treatment (median time was 67.5 days) | -The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting. |
| Progression-free Survival (PFS) | Up to 2 years | * Progression is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions). * PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. Patients alive without progression or lost to follow-up are censored. |
| Overall Survival (OS) | Up to 2 years | -OS is defined as the days from the date of treatment start and death from any cause. Participants alive or lost to follow-up are censored. |
| Time to Tumor Progression (TTP) | Up to 2 years | * Time to tumor progression is defined as the days from start of treatment until progressive disease. * Progression is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions). |
Countries
United States
Participant flow
Recruitment details
The study opened to participant enrollment on 06/06/2016 and closed to participant enrollment on 08/19/2019.
Participants by arm
| Arm | Count |
|---|---|
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine * Treatment will be given in a 28-day cycle.
* BVD-523 600 mg on a twice daily basis (at approximately 12-hour intervals).
* BVD-523 at 600 mg twice daily on its own for two weeks before initiating Cycle 1 treatment with gemcitabine and nab-paclitaxel.
* Nab-paclitaxel 125 mg/m\^2 on Days 1, 8, and 15 of each 28-day cycle over the course of 30-40 minutes.
* Gemcitabine 1000 mg/m\^2 on Days 1, 8, and 15 of each 28-day cycle over the course of 30 minutes.
* Mandatory biopsy at baseline and baseline at end of 2 week BVD-523 lead in. | 10 |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine * Treatment will be given in a 28-day cycle.
* First 2 patients enrolled: BVD-523 600 mg on a twice daily basis (at approximately 12-hour intervals), nab-paclitaxel 125 mg/m\^2 on Days 1, 8, and 15 of each 28-day cycle over the course of 30-40 minutes, and gemcitabine 1000 mg/m\^2 on Days 1, 8, and 15 of each 28-day cycle over the course of 30 minutes
* Remaining 6 patients enrolled: BVD-523 450 mg on a twice daily basis (at approximately 12-hour intervals), nab-paclitaxel 100 mg/m\^2 on Days 1, 8, and 15 of each 28-day cycle over the course of 30-40 minutes, and gemcitabine 800 mg/m\^2 on Days 1, 8, and 15 of each 28-day cycle over the course of 30 minutes
* Mandatory biopsy at baseline and at end of cycle 2 (if deemed safe for participant and feasible to obtain) | 8 |
| Total | 18 |
Baseline characteristics
| Characteristic | Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Total | Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine |
|---|---|---|---|
| Age, Continuous | 65.5 years | 63.5 years | 61.5 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 18 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 17 Participants | 7 Participants |
| Region of Enrollment United States | 10 participants | 18 participants | 8 participants |
| Sex: Female, Male Female | 3 Participants | 5 Participants | 2 Participants |
| Sex: Female, Male Male | 7 Participants | 13 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 11 / 12 | 5 / 6 |
| other Total, other adverse events | 12 / 12 | 6 / 6 |
| serious Total, serious adverse events | 8 / 12 | 4 / 6 |
Outcome results
Primary
Maximum Tolerated Dose (MTD) of BVD-523
-The maximum tolerated dose (MTD) is defined as the Dose Level 1 if 0 or 1 dose-limiting toxicities (DLTs) are seen in patients at that dose level or Dose Level -1 if 2+ DLTs are seen in Dose Level 1 but only 0 or 1 DLTs are seen in patients at Dose Level -1.
Time frame: Completion of cycle 1 for all dose de-escalation patients (1.8 years), the first cycle is 28 days for each individual patient
Population: -The MTD was not determined by DLTs in Dose De-escalation. 2 patients in Dose Expansion were treated at 600 mg but due to poor performance (inability to complete Cycle 1) the principal investigator felt it was reasonable to treat the remaining patients with 450 mg BVD-523 twice daily in the dose expansion portion of the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Maximum Tolerated Dose (MTD) of BVD-523 | 450 mg |
Secondary
Biochemical Response of Treatment Regimen
-The biochemical response (BR) is defined as more than 50% of decrease from baseline CA 19-9
Time frame: Through completion of treatment (median time was 37.5 days)
Population: -Participants with normal CA19-9 levels at baseline were excluded from this outcome measure and those who did not have an additional CA19-9 level drawn after baseline. Of the 5 participants analyzed in Dose Expansion Arm, 1 received 600 mg BVD-523 and 4 participants received 450 mg BVD-523.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Biochemical Response of Treatment Regimen | 3 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Biochemical Response of Treatment Regimen | 1 Participants |
Secondary
Overall Survival (OS)
-OS is defined as the days from the date of treatment start and death from any cause. Participants alive or lost to follow-up are censored.
Time frame: Up to 2 years
Population: Participants were not considered evaluable for this outcome measure if they were not evaluable for dose-limiting toxicities per protocol and any participants that were alive were censored.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Overall Survival (OS) | 13.8 months |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Overall Survival (OS) | 5.7 months |
Secondary
Progression-free Survival (PFS)
* Progression is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions). * PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. Patients alive without progression or lost to follow-up are censored.
Time frame: Up to 2 years
Population: Participants who did not have a follow-up CT scan were excluded from this outcome measure. The 2 participants analyzed in the Dose Expansion Arm received 450 mg BVD-523.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Progression-free Survival (PFS) | 85 days |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Progression-free Survival (PFS) | 39.5 days |
Secondary
Response Rate
* Response rate is the percentage of participants with best response of complete response or partial response per RECIST 1.1 * Complete response (CR): disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. * Partial response (PR): at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: Through completion of treatment (median time was 37.5 days)
Population: Participants who did not have a follow-up CT scan were excluded from this outcome measure. The 2 participants analyzed in the Dose Expansion arm received 450 mg of BVD-523.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Response Rate | 2 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Response Rate | 0 Participants |
Secondary
Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events
-The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.
Time frame: 30 days after completion of treatment (median time was 67.5 days)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 hyperkalemia | 2 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 3 lower GI hemorrhage | 1 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 hypoalbuminemia | 1 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 diarrhea | 5 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 hypocalcemia | 1 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 chills | 3 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 dehydration | 1 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 gastrointestinal pain | 1 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 arthralgia | 4 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 edema limbs | 3 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 back pain | 2 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 3 abdominal infection | 1 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 dizziness | 4 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 edema trunk | 1 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 headache | 3 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 mucositis oral | 2 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 peripheral sensory neuropathy | 5 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 fatigue | 3 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 numbness | 1 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 3 diarrhea | 2 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 insomnia | 2 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 fever | 5 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 anxiety | 1 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 nausea | 5 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 cough | 1 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 thrush | 1 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 dyspnea | 2 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 blurred vision | 3 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 epistaxis | 1 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 5 death due to disease progression | 1 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 5 adult respiratory distress syndrome | 1 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 3 nausea | 1 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 alopecia | 5 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 alanine aminotransferase increased | 2 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 rash acneiform | 3 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 dry mouth | 2 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 3 rash acneiform | 2 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 alkaline phosphtase | 2 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 rash maculo-papular | 4 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 taste change | 1 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 sweating | 1 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 4 blood bilirubin increased | 1 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1 scalp sun burned | 1 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 constipation | 5 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 hypertension | 3 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 3/4 neutrophil count decreased | 3 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 3 hypertension | 1 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 vomiting | 0 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 hyperhydrosis | 0 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 3 platelet count decreased | 1 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 pruritus | 0 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 dyspepsia | 1 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 myalgia | 0 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 lymphocyte count | 1 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 blood in stool | 0 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 3 vomiting | 2 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 anorexia | 3 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 white blood cell count decreased | 2 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 3 anorexia | 0 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 Hearing Impaired | 1 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 abdominal pain | 2 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 hypercalcemia | 2 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 3 abdominal pain | 0 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 acute kidney injury | 1 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 3 portal vein thrombosis | 0 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 hyperglycemia | 1 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 3 lung infection | 0 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 flatulence | 1 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 3 anemia | 0 Participants |
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 anemia | 3 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 3 anemia | 1 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 anemia | 1 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 Hearing Impaired | 0 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 blurred vision | 0 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 3 abdominal infection | 0 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 constipation | 2 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 diarrhea | 4 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 3 diarrhea | 0 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 dry mouth | 0 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 dyspepsia | 1 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 flatulence | 0 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 gastrointestinal pain | 0 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 mucositis oral | 2 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 nausea | 1 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 3 nausea | 1 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 taste change | 0 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 vomiting | 1 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 3 vomiting | 1 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 acute kidney injury | 0 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 3 lower GI hemorrhage | 0 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 chills | 1 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 edema limbs | 1 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 edema trunk | 0 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 fatigue | 2 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 fever | 2 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 thrush | 1 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 5 death due to disease progression | 1 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 alanine aminotransferase increased | 0 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 alkaline phosphtase | 0 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 4 blood bilirubin increased | 0 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 3/4 neutrophil count decreased | 1 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 3 platelet count decreased | 1 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 lymphocyte count | 0 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 white blood cell count decreased | 0 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 hypercalcemia | 0 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 hyperglycemia | 0 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 hyperkalemia | 0 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 hypoalbuminemia | 0 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 hypocalcemia | 0 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 dehydration | 1 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 arthralgia | 1 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 back pain | 0 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 dizziness | 1 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 headache | 0 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 peripheral sensory neuropathy | 0 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 numbness | 0 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 insomnia | 1 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 anxiety | 1 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 cough | 1 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 dyspnea | 0 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 epistaxis | 0 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 5 adult respiratory distress syndrome | 0 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 alopecia | 3 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 rash acneiform | 4 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 3 rash acneiform | 0 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 rash maculo-papular | 0 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 sweating | 0 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1 scalp sun burned | 0 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 hypertension | 0 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 3 hypertension | 0 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 hyperhydrosis | 1 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 pruritus | 1 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 myalgia | 1 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 blood in stool | 1 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 anorexia | 1 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 3 anorexia | 1 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 1/2 abdominal pain | 2 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 3 abdominal pain | 1 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 3 portal vein thrombosis | 1 Participants |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Safety and Toxicity Profile of Treatment Regimen as Measured by Grade and Frequency of Adverse Events | Grade 3 lung infection | 1 Participants |
Secondary
Time to Tumor Progression (TTP)
* Time to tumor progression is defined as the days from start of treatment until progressive disease. * Progression is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).
Time frame: Up to 2 years
Population: Participants who did not have a follow-up CT scan were excluded from this outcome measure. The 2 participants analyzed in the Dose Expansion Arm received 450 mg BVD-523.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose De-escalation: BVD-523/Nab-paclitaxel/Gemcitabine | Time to Tumor Progression (TTP) | 85 days |
| Dose Expansion: BVD-523/Nab-paclitaxel/Gemcitabine | Time to Tumor Progression (TTP) | 39.5 days |