Primary Outcome Measures: | |
1. |
Dose Limiting Toxicities (DLT) - (safety lead in) [ Time Frame: Up to 28 days ]
Incidence of dose limiting toxicities. |
2. |
Overall Survival (OS) [ Time Frame: Up to 35 months ]
OS is defined as the time from the date of randomization until the date of death from any cause. |
3. |
Safety assessed by Adverse Events (AEs) [ Time Frame: Up to 29 months ]
An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. |
4. |
Safety assessed by incidence of serious adverse events (SAE) [ Time Frame: Up to 29 months ]
Adverse Event (AE) is considered "serious" if the investigator or sponsor view any of the following outcomes: Death, life-threatening, persistent or significant disability/incapacity, congenital anomaly or birth defect, hospitalization, or medically important event. |
5. |
Safety assessed by incidence of treatment emergent adverse events (TEAE) [ Time Frame: Up to 27 months ]
Treatment Emergent Adverse Event (TEAE) is defined as any AE which starts, or worsens, after the first dose of study drug through 30 days after the last dose of study drug. |
6. |
Number of participants with laboratory value abnormalities and/or adverse events (AEs) [ Time Frame: Up to 27 months ]
Number of participants with potentially clinically significant laboratory values. |
7. |
Number of participants with vital sign abnormalities and /or adverse events (AEs) [ Time Frame: Up to 29 months ]
Number of participants with potentially clinically significant vital sign values. |
8. |
Number of participants with electrocardiograms (ECG) abnormalities and or adverse events [ Time Frame: Up to 27 months ]
12-lead ECGs will be recorded. Prior to the ECG, participants should rest in supine position for 10 minutes. ECGs will be read and assessed locally. |
9. |
Number of participants with Eastern Cooperative Oncology Group (ECOG) performance status abnormalities and or adverse events [ Time Frame: Up to 29 months ]
Number of participants with potentially clinically significant ECOG performance status values. ECOG grades 0-5, where 0 = Fully active, able to carry on all pre-disease performance without restriction; 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work; 2 = Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours; 3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4 = Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair and 5 = Dead. |
Secondary Outcome Measures: | |
1. |
Progression Free Survival (PFS) [ Time Frame: Up to 35 months ]
PFS is defined as the time from the date of randomization until the date of radiological progressive disease (PD) per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 by investigator evaluation or death from any cause, whichever is earliest. |
2. |
Objective Response Rate (ORR) [ Time Frame: Up to 35 months ]
ORR is defined as the proportion of participants who have a best overall response of Complete Response (CR) or Partial Response (PR) as assessed by investigator evaluation per RECIST 1.1. |
3. |
Number of anti-drug antibody (ADA) Positive Participants [ Time Frame: Up to 29 months ]
Immunogenicity will be measured by the number of participants that are ADA positive. |
4. |
Disease Control Rate (DCR) [ Time Frame: Up to 35 months ]
DCR is defined as the proportion of participants who have best overall response of stable disease, complete response (CR) or partial response (PR) as assessed by investigator evaluation per RECIST 1.1 |
5. |
Duration Of Response (DOR) [ Time Frame: Up to 35 months ]
DOR is defined as the time from the date of the first response (CR/PR) until the date of progressive disease as assessed by investigator evaluation per RECIST 1.1 or date of death from any cause, whichever is earliest. |
6. |
Change in CA (Cancer Antigen) 19-9 [ Time Frame: Baseline up to 27 months ]
Change from baseline in serum CA19-9 will be assessed. |
7. |
PK of zolbetuximab: Concentration Immediately Prior to Dosing (Ctrough) [ Time Frame: Up to 29 months ]
Ctrough will be derived from the PK serum samples collected. |
8. |
PK of paclitaxel: Area Under the Concentration-time Curve from the Time of Dosing Extrapolated to Time Infinity (AUCinf) [ Time Frame: Up to 30 days ]
AUCinf will be derived from the PK plasma samples collected. |
9. |
PK of paclitaxel: Area Under the Concentration-time Curve from the Time of Dosing Until the Last Measurable Concentration (AUClast) [ Time Frame: Up to 30 days ]
AUClast will be derived from the PK plasma samples collected. |
10. |
PK of paclitaxel: Maximum Concentration (Cmax) [ Time Frame: Up to 30 days ]
Cmax will be derived from the PK plasma samples collected. |
11. |
PK of paclitaxel: Time of Maximum Concentration (Tmax) [ Time Frame: Up to 30 days ]
Tmax will be derived from the PK plasma samples collected. |
12. |
PK of paclitaxel: Terminal Elimination Half-life (T1/2) [ Time Frame: Up to 30 days ]
T1/2 will be derived from the PK plasma samples collected. |
13. |
PK of paclitaxel: Clearance (CL) [ Time Frame: Up to 30 days ]
CL will be derived from the PK plasma samples collected. |
14. |
PK of paclitaxel: Volume of Distribution During the Terminal Phase (Vz) [ Time Frame: Up to 30 days ]
Vz will be derived from the PK plasma samples collected. |
15. |
PK of gemcitabine: Area Under the Concentration-time Curve from the Time of Dosing Extrapolated to Time Infinity (AUCinf) [ Time Frame: Up to 30 days ]
AUCinf will be derived from the PK plasma samples collected. |
16. |
PK of gemcitabine: Area Under the Concentration-time Curve from the Time of Dosing Until the Last Measurable Concentration (AUClast) [ Time Frame: Up to 30 days ]
AUClast will be derived from the PK plasma samples collected. |
17. |
PK of gemcitabine: Maximum Concentration (Cmax) [ Time Frame: Up to 30 days ]
Cmax will be derived from the PK plasma samples collected. |
18. |
PK of gemcitabine: Time of Maximum Concentration (Tmax) [ Time Frame: Up to 30 days ]
Tmax will be derived from the PK plasma samples collected. |
19. |
PK of gemcitabine: Terminal Elimination Half-life (T1/2) [ Time Frame: Up to 30 days ]
T1/2 will be derived from the PK plasma samples collected. |
20. |
PK of gemcitabine: Clearance (CL) [ Time Frame: Up to 30 days ]
CL will be derived from the PK plasma samples collected. |
21. |
PK of gemcitabine: Volume of Distribution During the Terminal Phase (Vz) [ Time Frame: Up to 30 days ]
Vz will be derived from the PK plasma samples collected. |