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Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

All Drugs and Chemicals

Tin Fluorides

Patients will be treated with VB6-845 as a monotherapy IV infusion, once weekly in 4-week cycles. Patients will continue to receive treatment up until the treatment stopping criteria or patient withdrawal criteria are met.

Dose escalation will begin at a dose level of 1.00 mg/kg. Doses will be escalated according to the modified Fibonacci design with dose multipliers of 2.00, 1.67, 1.50, 1.40, and 1.33.

Intravenous infusion once weekly for 4 weeks

VB6-845

Wendy Cuthbert

The purpose of this study is to determine the maximum tolerated dose (MTD) of VB6-845 and to evaluate the safety and tolerability of VB6-845 when administered as a monotherapy IV infusion to patients with advanced solid tumour of epithelial origin.

The primary study objective of this Phase 1 trial was to determine the maximum tolerated dose (MTD) of VB6-845 and evaluate the safety and tolerability of VB6-845 when administered as a monotherapy intravenous (IV) infusion (over 3 hours), once weekly in 4-week cycles, to subjects with EpCAM positive advanced solid tumours of epithelial origin.

Secondary objectives included evaluating the pharmacokinetic profile and immunogenicity of VB6-845 and assessing exploratory efficacy of VB6-845.

Dose cohorts of 3-6 subjects with EpCAM positive advanced solid tumours of epithelial origin are to be entered into the study. The starting dose is defined as 1.00 mg/kg, which is 1/10 of the no observed adverse effect level (NOAEL) reached in preclinical studies. Doses are to be escalated according to the modified Fibonacci design until 2 out of 3 or 2 out of 6 subjects experienced a Dose Limiting Toxicity (DLT). The MTD is to be reached when \<2 out of 6 subjects experienced a DLT. An additional 12 subjects are to be enrolled at the MTD for further characterization of VB6-845 at that level.

Regardless of dose cohort, subjects are to continue to receive treatment until an unacceptable toxicity occurred, all lesions completely disappeared or disease progression is determined.

Study of the Safety of VB6-845 in Patients With Advanced Solid Tumours of Epithelial Origin

A Phase I, Escalating Dose Study of VB6-845, a Recombinant Fusion Protein Targeting EpCAM, in Patients With Advanced Solid Tumours of Epithelial Origin

Sesen Bio, Inc.

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Adenocarcinoma

Pancreatic Neoplasms

Gastrointestinal Diseases

Gastrointestinal Neoplasms

Endocrine Gland Neoplasms

Pancreatic Diseases

Digestive System Neoplasms

Endocrine System Diseases

Pancreatic Cancer

Antineoplastic Agents

Gemcitabine

Capecitabine

Paclitaxel

Irinotecan

Albumin-Bound Paclitaxel

Cisplatin

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Topoisomerase I Inhibitors

Enzyme Inhibitors

Gemcitabine: 500 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle

Nab-paclitaxel: 40 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle

Capecitabine: 500 mg BID, PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle

Cisplatin: 20 mg/m\^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle

Irinotecan: 20 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle

Gemcitabine 500 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle

Nab-paclitaxel 60 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle

Capecitabine: 500 mg BID: PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle

Cisplatin: 20 mg/m\^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle

Irinotecan: 20 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle

Gemcitabine: 500 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle

Nab-paclitaxel: 80 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle

Capecitabine: 500 mg BID, PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle

Cisplatin 20 mg/m\^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle

Irinotecan:20 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle

Gemcitabine:500 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle

Nab-paclitaxel:100 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle

Capecitabine:500 PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle

Cisplatin:20 mg/m\^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle

Irinotecan:20 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle

Gemcitabine:500 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle

Nab-paclitaxel:125 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle

Capecitabine: 500 mg BID, PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle

Cisplatin:20 mg/m\^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle

Irinotecan: 20 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle

Gemcitabine: 500 mg/m\^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle

Nab-paclitaxel:40 mg/m\^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle

Capecitabine:500 mg BID, PO twice daily (BID); Days 1-14 of a 21 day cycle

Cisplatin:20 mg/m\^2, IV over 60 minutes; Days 4 and 11 of a 21 day cycle

Irinotecan: 20 mg/m\^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle

Gemcitabine: 500 mg/m\^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle

Nab-paclitaxel:60 mg/m\^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle

Capecitabine:500mg BID, PO twice daily (BID); Days 1-14 of a 21 day cycle

Cisplatin:20 mg/m\^2, IV over 60 minutes; Days 4 and 11 of a 21 day cycle

Irinotecan: 20 mg/m\^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle

Gemcitabine: 500 mg/m\^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle

Nab-paclitaxel:80 mg/m\^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle

Capecitabine:500mg BID, PO twice daily (BID); Days 1-14 of a 21 day cycle

Cisplatin:20 mg/m\^2, IV over 60 minutes; Days 4 and 11 of a 21 day cycle

Irinotecan: 20 mg/m\^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle

Nab-paclitaxel

Dung Le, MD

The purpose of this study is to evaluate the clinical activity of gemcitabine, nab-paclitaxel, capecitabine, cisplatin, and irinotecan (GAX-CI) in patients with metastatic pancreatic cancer.

This was a two-part, single-institution, open-label, dose-escalation, phase 1/2 study to evaluate the clinical activity of gemcitabine, nab-paclitaxel, capecitabine, cisplatin, and irinotecan in patients with metastatic pancreatic cancer.

Part 1 of the study was a Phase 1 3 + 3 dose escalation study designed to evaluate the maximally tolerated dose (MTD) and safety of increasing doses of nab-paclitaxel in combination with gemcitabine, capecitabine, cisplatin, and irinotecan. There were two cohorts of dose escalations. The two cohorts differed based on the treatment cycle length (28 days for Cohort 1 and 21 days for Cohort 2). Dose escalation started with Cohort 1. Enrollment for Cohort 2 dose level 1 began once dose level 2 of Cohort 1 was shown to be safe and did not exceed MTD.

Part 2 was a Phase 2 expansion cohort study for the evaluation of efficacy once the MTD had been determined.

A Study of Gemcitabine, Nab-paclitaxel, Capecitabine, Cisplatin, and Irinotecan in Metastatic Pancreatic Cancer

A Phase I/II Study of Gemcitabine, Nab-paclitaxel, Capecitabine, Cisplatin, and Irinotecan (GAX-CI) in Combination in Metastatic Pancreatic Cancer

Dose escalation (phase I portion of the trial only) to determine the MTD in mg/m\^2. Participants received Gemcitabine: 500 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle (Cohort 1) or Days 4 and 11 of a 21 day cycle (Cohort 2)

Dose escalation (phase I portion of the trial only) to determine the MTD in mg/m\^2. Participants received Nab-paclitaxel: 20, 40, 60, 80, 100,125 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle (Cohort 1) or Days 4 and 11 of a 21 day cycle (Cohort 2)

Dose escalation (phase I portion of the trial only) to determine the MTD in mg for twice daily (BID) use. Participants received Capecitabine: 500 mg BID, PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle (Cohort 1) or Days 1-14 of a 21 day cycle (Cohort 2)

Dose escalation (phase I portion of the trial only) to determine the MTD in mg/m\^2. Participants received Cisplatin:20 mg/m\^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle (Cohort 1) or Days 4 and 11 of a 21 day cycle (Cohort 2)

Dose escalation (phase I portion of the trial only) to determine the MTD in mg/m\^2. Participants received Irinotecan: 20 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle (Cohort 1) or Days 4 and 11 of a 21 day cycle (Cohort 2)

PFS is defined as the number of months from the date of first dose to disease progression (progressive disease \[PD\] or relapse from complete response \[CR\] as assessed using RECIST 1.1 criteria) or death due to any cause. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =\>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is \>20% increase in sum of diameters of target lesions, Stable Disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions. Estimation based on the Kaplan-Meier curve.

Number of patients who received the MTD (Cohort 1, Dose Level 5) that experienced a limiting toxicity. Limiting toxicity was defined as a grade 3 or above treatment-related toxicity, with the following exceptions: 1. Grade 3 anemia that resolves to \< grade 2 within 7 days; 2. Grade 3 thrombocytopenia without clinically significant bleeding that resolves to \< grade 2 within 7 days; 3. Grade 3 or 4 neutropenia that resolves to \<grade 2 within 7 days; 4. Grade 3 or 4 leucopenia/lymphopenia; 5. Grade 3 nausea, vomiting, or diarrhea that resolves to \<grade 2 within 72 hours; 6. Grade 3 or 4 asymptomatic laboratory values that resolve to \< grade 2 within 7 days; 7. Grade 3 dermatologic AEs that are considered mild in severity but only considered grade 3 because of \>30% body surface involvement; 8. Grade 3 fatigue lasting less than 72 hours. This study used the descriptions and grading scales found in the revised NCI CTCAE fV 5.0 for adverse event reporting.

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

This study used the descriptions and grading scales found in the revised National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 for adverse event reporting. During the survival follow-up portion of the trial, patients were evaluated for all-cause mortality past the time frame for treatment and the assessment of adverse events.

Gemcitabine: 500 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle

Nab-paclitaxel: 40 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle

Capecitabine: 500 mg BID, PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle

Cisplatin: 20 mg/\^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle

Irinotecan: 20 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle

Phase 1, Cohort 1, Dose Level 1

Gemcitabine: 500 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle

Nab-paclitaxel: 60 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle

Capecitabine: 500 mg BID, PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle

Cisplatin: 20 mg/m\^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle

Irinotecan: 20 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle

Phase 1, Cohort 1, Dose Level 2

Gemcitabine: 500 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle

Nab-paclitaxel: 80 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle

Capecitabine: 500 mg BID, PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle

Cisplatin: 20 mg/m\^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle

Irinotecan: 20 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle

Phase 1, Cohort 1, Dose Level 3

Gemcitabine: 500 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle

Nab-paclitaxel: 100 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle

Capecitabine: 500 mg BID, PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle

Cisplatin: 20 mg/m\^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle

Irinotecan: 20 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle

Phase 1, Cohort 1, Dose Level 4

Gemcitabine: 500 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle

Nab-paclitaxel: 125 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle

Capecitabine: 500 mg BID, PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle

Cisplatin: 20 mg/m\^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle

Irinotecan: 20 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle

Phase 1, Cohort 1, Dose Level 5

Phase 1, Cohort 2, Dose Level 1

Gemcitabine: 500 mg/m\^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle

Nab-paclitaxel:60 mg/m\^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle

Capecitabine:500 mg BID, PO twice daily (BID); Days 1-14 of a 21 day cycle

Cisplatin:20 mg/m\^2, IV over 60 minutes; Days 4 and 11 of a 21 day cycle

Irinotecan: 20 mg/m\^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle

Phase 1, Cohort 2, Dose Level 2

Gemcitabine: 500 mg/m\^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle

Nab-paclitaxel:80 mg/m\^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle

Capecitabine:500 mg BID, PO twice daily (BID); Days 1-14 of a 21 day cycle

Cisplatin:20 mg/m\^2, IV over 60 minutes; Days 4 and 11 of a 21 day cycle

Irinotecan: 20 mg/m\^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle

Phase 1, Cohort 2, Dose Level 3

Phase 2 MTD Dose Expansion

Phase 2, MTD Dose Expansion

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

ECOG 0

ECOG 1

The ECOG scale measures performance status , which scores ranging from 0-5: 0=fully active , performs without restrictions, 1=can ambulate,but restricted in physical strenuous activity,2=ambulatory and capable of self care , but unable to work , active for \>50%of waking hours,3=limited self care, confined to bed or chair for \>50%of waking hours,4=completely disabled, totally confined tp bed/chair,5= deceased

Eastern Cooperative Oncology Group (ECOG)

Dung Le, M.D.

Gemcitabine:500 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle (Cohort 1) or Days 4 and 11 of a 21 day cycle (Cohort 2)

Nab-paclitaxel:20, 40, 60, 80, 100,125 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle (Cohort 1) or Days 4 and 11 of a 21 day cycle (Cohort 2)

Capecitabine: 500 mg BID, PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle (Cohort 1) or Days 1-14 of a 21 day cycle (Cohort 2)

Cisplatin:20 mg/m\^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle (Cohort 1) or Days 4 and 11 of a 21 day cycle (Cohort 2)

Irinotecan: 20 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle (Cohort 1) or Days 4 and 11 of a 21 day cycle (Cohort 2)

Phase I

Cohort 1 cycle schedule was selected for the MTD (Days 1 and 15 of a 28 day cycle)

Maximum Tolerated Dose (MTD) of Gemcitabine.

Gemcitabine:500 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle (Cohort 1) or Days 4 and 11 of a 21 day cycle (Cohort 2)

Nab-paclitaxel:20, 40, 60, 80, 100,125 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle (Cohort 1) or Days 4 and 11 of a 21 day cycle (Cohort 2)

Capecitabine: 500 mg BID, PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle (Cohort 1) or Days 1-14 of a 21 day cycle (Cohort 2)

Cisplatin:20 mg/m\^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle cycle (Cohort 1) or Days 4 and 11 of a 21 day cycle (Cohort 2)

Irinotecan: 20 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle (Cohort 1) or Days 4 and 11 of a 21 day cycle (Cohort 2)

Phase 1

Maximum Tolerated Dose (MTD) of Nab-paclitaxel.

Cohort 1 cycle schedule was selected for the MTD (Days 1-7 and 15-21 of a 28 day cycle)

Maximum Tolerated Dose (MTD) of Capecitabine.

Maximum Tolerated Dose (MTD) of Cisplatin.

Maximum Tolerated Dose (MTD) of Irinotecan.

Phase 1 MTD/ Phase 2

Per the clinical trial design, PFS analyses included all subjects who received the MTD (Cohort 1, Dose Level 5). Since the enrollment criteria and dose are the same, combining those who are treated at MTD at both phases increase the power and enable to estimate the treatment effect with increased precision. This included the 6 subjects enrolled in the Phase 1 portion of the trial and the 8 subjects enrolled in the Phase 2 portion of the trial for a total of 14 subjects.

Progression-free Survival (PFS) Using RECIST 1.1 Criteria

Per the clinical trial design, safety analyses included all subjects who received the MTD (Cohort 1, Dose Level 5). Since the enrollment criteria and dose are the same, combining those who are treated at MTD at both phases enable to estimate the toxicity rate with increased precision. This included the 6 subjects enrolled in the Phase 1 portion of the trial and the 8 subjects enrolled in the Phase 2 portion of the trial for a total of 14 subjects.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of the Safety of VB6-845 in Patients With Advanced Solid Tumours of Epithelial Origin	NCT00481936	Neoplasms, Glan...	VB6-845	18 Years -	Sesen Bio, Inc.
A Study of Gemcitabine, Nab-paclitaxel, Capecitabine, Cisplatin, and Irinotecan in Metastatic Pancreatic Cancer	NCT03535727	Adenocarcinoma Pancreatic Neop... Neoplasm, Gland... Neoplasms Neoplasms Pancr... Digestive Syste... Endocrine Gland... Digestive Syste... Pancreatic Dise... Endocrine Syste...	Nab-paclitaxel Gemcitabine Capecitabine Cisplatin Irinotecan Nab-paclitaxel Gemcitabine Capecitabine Cisplatin Irinotecan	18 Years - 76 Years	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study of the Safety of VB6-845 in Patients With Advanced Solid Tumours of Epithelial Origin	NCT00481936	Neoplasms, Glan...	VB6-845	18 Years -	Sesen Bio, Inc.

Spots Global Cancer Trial Database for neoplasm, glandular