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)
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.
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.
Single group
DT2216
DrugA proteolysis-targeting chimera (PROTAC) degrader, single-use vial, via intravenous (into the vein) infusion.
Paclitaxel
DrugAn antimicrotubule agent, multi-dose vial, via intravenous (into the vein) infusion per institutional standard.
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).
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.
Grade 4 Treatment-Related Toxicity Rate
Grade 4 treatment-related toxicity rate is the percentage of participants experiencing at least one treatment-related grade 4 adverse event (AE) with treatment attribution of possibly, probably or definite based on NCI Common Toxicity Criteria for Adverse Events version 5 (CTCAEv5) as reported on case report forms.
Overall Response Rate (ORR)
ORR is defined as the proportion of participants who achieve partial response (PR) or better based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) criteria on treatment.
Median Progression Free Survival (PFS)
PFS based on Kaplan-Meier method is defined as the time from study entry to documented disease progression (PD) per RECIST 1.1 or death. Participants alive without PD are censored at date of last disease assessment.
Median Duration of Response (DOR)
DOR based on Kaplan-Meier method is defined as the time from PR or better until documented PD per RECIST 1.1 or death. Participants alive without PD are censored at date of last disease assessment.
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Elizabeth Stover, MD, PhD
Lead sponsor
Dana-Farber Cancer Institute
Sponsor institution
United States Department of Defense
Collaborator
Dialectic Therapeutics, Inc
Collaborator
American Society of Clinical Oncology
Collaborator
