A Study of DMOT4039A in Participants With Unresectable Pancreatic or Platinum-Resistant Ovarian Cancer

A Phase I, Open Label Study of the Safety and Pharmacokinetics of Escalating Doses of DMOT4039A in Patients With Unresectable Pancreatic or Platinum-Resistant Ovarian Cancer

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01469793

Enrollment

Registered

2011-11-10

Start date

2011-11-30

Completion date

2015-12-31

Last updated

2017-01-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Ovarian Cancer

Brief summary

This multicenter, open-label, dose-escalating study will assess the safety, tolerability, and pharmacokinetics of DMOT4039A in participants with unresectable pancreatic or platinum-resistant ovarian cancer. Cohorts of participants will receive multiple ascending intravenous doses of DMOT4039A.

Interventions

DRUGDMOT4039A

DMOT4093A will be administered by intravenous infusion on either a Q3W or a Q1W dosing schedule, in 21-day cycles.

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

Inclusion criteria

* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 * Histologically documented, incurable, locally advanced or metastatic disease for which no standard therapy exists, consisting of one of the following: Unresectable pancreatic ductal adenocarcinoma or platinum-resistant ovarian cancer * Measureable disease, defined as at least one bi-dimensionally measurable non-lymph node lesion greater than or equal to (\>/=) 1 centimeter (cm) in long-axis diameter on spiral computed tomography (CT) scan or at least one bi-dimensionally measurable lymph node measuring \>/= 1.5 cm in short-axis diameter on spiral CT scan * Adequate hematological, renal and liver function

Exclusion criteria

* Treatment with anti-tumor therapy, including chemotherapy, biologic, experimental or hormonal therapy, within 4 weeks prior to Day 1 * Known active infection * Current Grade \>/= 2 toxicity (except for alopecia, anorexia and fatigue) from prior therapy or Grade \>/= 2 neuropathy * Untreated or active cerebral nervous system metastases * Pregnant or breastfeeding women

Design outcomes

Primary

Measure	Time frame
Maximum Tolerated Dose (MTD) of DMOT4039A	Days 1 to 21 of Cycle 1 (1 cycle=21 days)
Number of Participants With Dose-Limiting Toxicities (DLTs)	Days 1 to 21 of Cycle 1 (1 cycle=21 days)
Recommended Phase 2 Dose (RP2D) of DMOT4039A	Days 1 to 21 of Cycle 1 (1 cycle=21 days)

Secondary

Measure	Time frame
Maximum Observed Concentration (Cmax) of DMOT4039A Total Antibody	Q3W: Pre-infusion (0 hrs), 0.5, 4, 24, 48 hrs, and 7, 9/10, 14, 16/17 days post-infusion in Cycle 1; Q1W: Pre-infusion (0 hrs), 0.5, 48 hrs post Day 1, 8, 15 infusions, 4, 24 hrs post Day 1 infusion in Cycle 1 (Infusion length=1.5 hrs) (1 cycle=21 days)
Cmax of acMMAE	Q3W: Pre-infusion (0 hrs), 0.5, 4, 24, 48 hrs, and 7, 9/10, 14, 16/17 days post-infusion in Cycle 1; Q1W: Pre-infusion (0 hrs), 0.5, 48 hrs post Day 1, 8, 15 infusions, 4, 24 hrs post Day 1 infusion in Cycle 1 (Infusion length=1.5 hrs) (1 cycle=21 days)
Cmax of Unconjugated MMAE	Q3W: Pre-infusion (0 hrs), 0.5, 4, 24, 48 hrs, and 7, 9/10, 14, 16/17 days post-infusion in Cycle 1; Q1W: Pre-infusion (0 hrs), 0.5, 48 hrs post Day 1, 8, 15 infusions, 4, 24 hrs post Day 1 infusion in Cycle 1 (Infusion length=1.5 hrs) (1 cycle=21 days)
Total Clearance (CL) of DMOT4039A Total Antibody	Q3W: Pre-infusion (0 hrs), 0.5, 4, 24, 48 hrs, and 7, 9/10, 14, 16/17 days post-infusion in Cycle 1; Q1W: Pre-infusion (0 hrs), 0.5, 48 hrs post Day 1, 8, 15 infusions, 4, 24 hrs post Day 1 infusion in Cycle 1 (Infusion length=1.5 hrs) (1 cycle=21 days)
CL of acMMAE	Q3W: Pre-infusion (0 hrs), 0.5, 4, 24, 48 hrs, and 7, 9/10, 14, 16/17 days post-infusion in Cycle 1; Q1W: Pre-infusion (0 hrs), 0.5, 48 hrs post Day 1, 8, 15 infusions, 4, 24 hrs post Day 1 infusion in Cycle 1 (Infusion length=1.5 hrs) (1 cycle=21 days)
Half-life (t1/2) of DMOT4039A Total Antibody	Q3W: Pre-infusion (0 hrs), 0.5, 4, 24, 48 hrs, and 7, 9/10, 14, 16/17 days post-infusion in Cycle 1; Q1W: Pre-infusion (0 hrs), 0.5, 48 hrs post Day 1, 8, 15 infusions, 4, 24 hrs post Day 1 infusion in Cycle 1 (Infusion length=1.5 hrs) (1 cycle=21 days)
t1/2 of acMMAE	Q3W: Pre-infusion (0 hrs), 0.5, 4, 24, 48 hrs, and 7, 9/10, 14, 16/17 days post-infusion in Cycle 1; Q1W: Pre-infusion (0 hrs), 0.5, 48 hrs post Day 1, 8, 15 infusions, 4, 24 hrs post Day 1 infusion in Cycle 1 (Infusion length=1.5 hrs) (1 cycle=21 days)
Area Under the Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUC [0-inf]) of DMOT4039A Total Antibody	Q3W: Pre-infusion (0 hours [hrs]), 0.5, 4, 24, 48 hrs, and 7, 9/10, 14, 16/17 days post-infusion in Cycle 1; Q1W: Pre-infusion, 0.5, 48 hrs post Day 1, 8, 15 infusions, 4, 24 hrs post Day 1 infusion in Cycle 1 (Infusion length=1.5 hrs) (1 cycle=21 days)
Volume of Distribution at Steady State (Vss) of DMOT4039A Total Antibody	Q3W: Pre-infusion (0 hrs), 0.5, 4, 24, 48 hrs, and 7, 9/10, 14, 16/17 days post-infusion in Cycle 1; Q1W: Pre-infusion (0 hrs), 0.5, 48 hrs post Day 1, 8, 15 infusions, 4, 24 hrs post Day 1 infusion in Cycle 1 (Infusion length=1.5 hrs) (1 cycle=21 days)
Vss of acMMAE	Q3W: Pre-infusion (0 hrs), 0.5, 4, 24, 48 hrs, and 7, 9/10, 14, 16/17 days post-infusion in Cycle 1; Q1W: Pre-infusion (0 hrs), 0.5, 48 hrs post Day 1, 8, 15 infusions, 4, 24 hrs post Day 1 infusion in Cycle 1 (Infusion length=1.5 hrs) (1 cycle=21 days)
Percentage of Participants With Anti-Therapeutic Antibodies (ATAs)	Baseline (pre-infusion [0 hrs] on Day 1 Cycle 1); Post-Baseline (assessed at pre-infusion [0 hrs] on Day 1 of Cycles 2-4 and at study completion/early termination [up to 30 days after Cycle 32]) (1 cycle=21 days)
Percentage of Participants With Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)	Baseline up to PD or death, whichever occurred first (assessed at Day 1, every 2 cycles thereafter [Cycles 2, 4, 6, 8, 10, 12, 14, and 16]; at study completion/early withdrawal [up to 30 days after Cycle 32]) (1 cycle=21 days)
Duration of Objective Response (DOR) According to RECIST v1.1	From the date of initial PR or CR up to PD or death, whichever occurred first (assessed at Day 1, every 2 cycles thereafter [Cycles 2, 4, 6, 8, 10, 12, 14, and 16]; at study completion/early withdrawal [up to 30 days after Cycle 32]) (1 cycle=21 days)
Progression-free Survival (PFS) According to RECIST v1.1	Day 1 up to PD or death, whichever occurred first (assessed at Day 1, every 2 cycles thereafter [Cycles 2, 4, 6, 8, 10, 12, 14, and 16]; at study completion/early withdrawal [up 30 days after Cycle 32]) (1 cycle=21 days)
t1/2 of Unconjugated MMAE	Q3W: Pre-infusion (0 hrs), 0.5, 4, 24, 48 hrs, and 7, 9/10, 14, 16/17 days post-infusion in Cycle 1; Q1W: Pre-infusion (0 hrs), 0.5, 48 hrs post Day 1, 8, 15 infusions, 4, 24 hrs post Day 1 infusion in Cycle 1 (Infusion length=1.5 hrs) (1 cycle=21 days)
AUC (0-inf) of Antibody-Conjugated Monomethyl Auristatin E (acMMAE)	Q3W: Pre-infusion (0 hrs), 0.5, 4, 24, 48 hrs, and 7, 9/10, 14, 16/17 days post-infusion in Cycle 1; Q1W: Pre-infusion (0 hrs), 0.5, 48 hrs post Day 1, 8, 15 infusions, 4, 24 hrs post Day 1 infusion in Cycle 1 (Infusion length=1.5 hrs) (1 cycle=21 days)
AUC (0-inf) of Unconjugated MMAE	Q3W: Pre-infusion (0 hrs), 0.5, 4, 24, 48 hrs, and 7, 9/10, 14, 16/17 days post-infusion in Cycle 1; Q1W: Pre-infusion (0 hrs), 0.5, 48 hrs post Day 1, 8, 15 infusions, 4, 24 hrs post Day 1 infusion in Cycle 1 (Infusion length=1.5 hrs) (1 cycle=21 days)

Countries

Netherlands, United States

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Mar 8, 2026