DT2216 + Paclitaxel in Platinum-Resistant Ovarian Cancer
A Phase 1b Study of BCL-XL Degrader DT2216 in Combination With Weekly Paclitaxel in Recurrent Platinum-resistant Ovarian Cancer
2 other identifiers
interventional
30
1 country
3
Brief Summary
The purpose of this research study is determining the highest dose of the study drug DT2216 in combination with paclitaxel that can be safely and tolerably administered in recurrent ovarian cancer. The names of the study drugs involved in this study are:
- DT2216 (a type of proteolysis-targeting chimera degrader of BCL-XL protein)
- Paclitaxel (a type of antimicrotubule agent)
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1 ovarian-cancer
Started Sep 2025
3 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 8, 2025
CompletedFirst Posted
Study publicly available on registry
May 9, 2025
CompletedStudy Start
First participant enrolled
September 22, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 30, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 30, 2027
April 21, 2026
April 1, 2026
1.3 years
April 8, 2025
April 20, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
DT2216 Maximum Tolerated Dose (MTD)
The DT2216 MTD in combination with paclitaxel is determined by the number of participants who experience dose-limiting toxicity (DLT) during cycle 1 and up to start of cycle 2. Dose (de-)escalation rules and the related selection of the MTD are based on the Bayesian Optimal Interval Design (BOIN).
Assessed on Day 1, 4, 8, 11, 15, 18, 22 and 25 on cycle 1 and up to start of cycle 2; cycle 1 duration=28 days plus 14 days maximum until start of cycle 2, for a maximum time frame of 42 days.
Number of Participants Experiencing a Dose-Limiting Toxicity (DLT)
A DLT is defined as including grade 3 or higher non-hematologic toxicity with some exclusions and specific hematologic toxicities, both not clearly due to the underlying disease or extraneous causes, along with any death, treatment delays\>14 days and inability to receive at least 75% of assigned doses of each agent.
Assessed on Day 1, 4, 8, 11, 15, 18, 22 and 25 on cycle 1 and up to start of cycle 2; cycle 1 duration=28 days plus 14 days maximum until start of cycle 2, for a maximum time frame of 42 days.
Secondary Outcomes (4)
Grade 4 Treatment-Related Toxicity Rate
Assessed on Days 1, 4, 8, 11, 15, 18, 22 and 25 of each cycle on treatment (cycle duration=28 day). Treatment duration is not fixed and thus observation time is variable.
Overall Response Rate (ORR)
Assessed radiologically every 8 weeks on treatment up to 24 cycles (each cycle is 28 days), then every 16 weeks on treatment thereafter; treatment duration is not fixed, and thus observation time is variable.
Median Progression Free Survival (PFS)
Assessed radiologically every 8 weeks on treatment up to 24 cycles (each cycle is 28 days), then every 16 weeks on treatment thereafter, or in follow-up (the earlier of 30-days post-treatment discontinuation or death).
Median Duration of Response (DOR)
Assessed radiologically every 8 weeks on treatment up to 24 cycles (each cycle is 28 days), then every 16 weeks on treatment thereafter, or in follow-up (the earlier of 30-days post-treatment discontinuation or death).
Study Arms (1)
DT2216 + Paclitaxel
EXPERIMENTALDose de-escalation and escalation for the DT2216 and Pacllitaxel combination will be guided using a Bayesian Optimal Interval (BOIN) design. Enrolled participants will complete: * Baseline visit * Imaging every 2 cycles * ECG Days 1, 8, and 15 of Cycle 1 and Day 1 of Cycle 2. * Research blood sample Days 1, 2, 4, 8, 15, 16, 18 and 22 of Cycle 1 and Day 1 of every cycle. * Cycle 1 (28 day cycles): * Days 1, 4, 8, 11, 15, 18, 22, and 25: Predetermined dose of DT2216 1x daily * Days 1, 8, 15: Predetermined dose of Paclitaxel 1x daily * Cycle 2 through end of treatment (28 day cycles): * Days 1, 4, 8, 11, 15, 18, 22, 25: Predetermined dose of DT2216 1x daily * Days 1, 8, 15: Predetermined dose of Paclitaxel 1x daily * End of treatment visit with imaging * 30 day follow up visit
Interventions
A proteolysis-targeting chimera (PROTAC) degrader, single-use vial, via intravenous (into the vein) infusion.
An antimicrotubule agent, multi-dose vial, via intravenous (into the vein) infusion per institutional standard.
Eligibility Criteria
You may qualify if:
- Participants must have histologically confirmed relapsed or refractory ovarian cancer (including epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal carcinoma).
- Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non- nodal lesions and short axis for nodal lesions) as ≥20 mm (≥2 cm) by chest x-ray or as ≥10 mm (≥1 cm) with CT scan, MRI, or calipers by clinical exam.
- Participants must have received at least one prior platinum-based chemotherapeutic regimen for primary management of disease.
- Participants must have been treated with at least one line of standard-of-care platinum-based chemotherapy but otherwise there is no limit on lines of prior systemic therapy. For participants who received recent palliative radiotherapy, the radiation treatment must have been completed at least two weeks prior to initiating study treatment. Prior dose-dense paclitaxel as part of initial treatment and prior treatment with weekly paclitaxel in the recurrent setting is permitted; however, at least 6 months must have elapsed between the last dose of weekly paclitaxel and protocol treatment initiation.
- Age ≥18 years.
- ECOG performance status 0-2.
- Participants must meet the following laboratory criteria:
- absolute neutrophil count ≥1000/mcL\*
- platelets ≥100,000/mcL\*
- hemoglobin ≥8 g/dL
- total bilirubin ≤ 1.5x institutional upper limit of normal (ULN)\*\*
- AST(SGOT)/ALT(SGPT) ≤3x institutional ULN\*\*\*
- PT/INR ≤ 1.5xinstitutional ULN
- Serum albumin ≥ 3.0 g/dL
- eGFR (glomerular filtration rate) ≥50 mL/min\*\*\*\*
- +14 more criteria
You may not qualify if:
- Prior treatment with weekly paclitaxel in the recurrent setting. Prior dose-dense paclitaxel as part of the initial treatment at diagnosis is allowed.
- Prior treatment with any BCL-XL inhibitor, such as navitoclax.
- Participants who are receiving any other investigational agents for this condition or received an investigational agent within 5 half-lives of the agent or 4 weeks, whichever is shorter.
- Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 1) except for alopecia. Participants with endocrine- related AEs who are adequately treated with hormone replacement or participants who have grade 2 neuropathy are eligible. Participants with grade 2 anemia likely related to prior treatment are eligible. Participants with a history of a thromboembolic event who are on stable therapeutic anticoagulation are eligible. Participants with asymptomatic grade 2 hypertension controlled with anti-hypertensive medications are eligible.
- Ongoing treatment with chronic immunosuppressants or systemic steroids \> 10 mg of prednisone daily (or equivalent). 10 mg daily of oral prednisone or less can be continued if clinically required.
- Known active central nervous system involvement with metastatic cancer, including leptomeningeal disease. Participants with previously treated brain metastases may enroll if the disease is stable for at least one month on imaging with no neurologic symptoms and participants are not receiving pharmacologic doses of glucocorticoids for this diagnosis.
- Prior organ transplantation or other cellular therapies such as Chimeric Antigen Receptor T-cells. Prior allogeneic stem cell transplantation (SCT) is allowed if there is no evidence of Graft Versus Host Disease and if participant meets other eligibility criteria listed. Prior autologous SCT is permitted if the participant meets the other eligibility criteria listed.
- History of major surgery within 8 weeks prior to first dose of study drug.
- History of clinically significant small or large bowel obstruction within 8 weeks prior to first dose of study drug (e.g. symptomatic, impairing nutrition, requiring nasogastric tube, requiring hospital admission).
- History of clinically significant ascites or pleural effusion requiring recurrent paracentesis or thoracentesis within 4 weeks prior to first dose of study drug.
- Dependence upon TPN or regular IV fluid resuscitation.
- History (≤2 weeks before the start of treatment with the study drug) of ongoing or active infections (Grade ≥ 2).
- Baseline prolongation of QTc interval (\> 470 msec) using Bazett's formula or history of Long QT Syndrome. Caution should be exercised with the use of concomitant medications that prolong the QTc interval.
- History of a bleeding complication within the past 4 weeks, or a clinically significant bleeding predisposition.
- Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, symptomatic angina pectoris, cardiac arrhythmia, on dialysis, on any organ transplant list; any medical condition for which the primary oncologist or principal investigator deems the participant an unsuitable candidate to receive DT2216 and/or paclitaxel; or psychiatric illness or other situations that would limit compliance with study requirements.
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Elizabeth Stover, MD, PhDlead
- United States Department of Defensecollaborator
- Dialectic Therapeutics, Inccollaborator
- American Society of Clinical Oncologycollaborator
Study Sites (3)
Beth Israel Deaconess Medical Center (BIDMC)
Boston, Massachusetts, 02115, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02115, United States
Brigham and Women's Hospital
Boston, Massachusetts, 02215, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Elizabeth Stover, MD, PhD
Dana-Farber Cancer Institute
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Sponsor-Investigator
Study Record Dates
First Submitted
April 8, 2025
First Posted
May 9, 2025
Study Start
September 22, 2025
Primary Completion (Estimated)
December 30, 2026
Study Completion (Estimated)
December 30, 2027
Last Updated
April 21, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- Data can be shared no earlier than 1 year following the date of publication
- Access Criteria
- Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu
The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.