DT2216 + Paclitaxel in Platinum-Resistant Ovarian Cancer

Exclusion Criteria

• •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.
• •History of allergic reactions attributed to compounds of similar chemical or biologic composition to DT2216 or paclitaxel. Participants with known allergy or hypersensitivity to paclitaxel or to its vehicle formulation may not enroll, except participants who have subsequently tolerated paclitaxel infusions after a hypersensitivity reaction with or without modifications to the pre-medications. If participants develop allergy or hypersensitivity to paclitaxel during treatment on the study, they may be able to remain on study via receiving paclitaxel with a desensitization procedure supervised by an allergy physician after a formal allergy consultation and discussion with the study PI.
• •Participants receiving any medications or substances that are strong inhibitors or inducers of the cytochrome P450 isoenzyme CYP3A4 or CYP2C8 are ineligible. Strong CYP3A4 or CYP2C8 inhibitors and inducers should be discontinued at least 2 weeks prior to the first dose of DT2216. As per paclitaxel product documentation, it is important to use caution with known substrates or inhibitors of the cytochrome P450 isoenzymes CYP3A4 and CYP2C8. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated medical reference. As part of the enrollment/informed consent procedures, the participant will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the participant is considering a new over-the-counter medicine or herbal product.
• •Pregnant females are excluded from this study because the effects of DT2216 on the developing fetus are unknown. Participants must have a negative pregnancy test result at screening (for females of childbearing potential). The test must be performed at the screening and Cycle 1 Day 1 visits. Participants of non-childbearing potential will have had at least continuous 12 months of natural (spontaneous) amenorrhea, and an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms), or have had surgical bilateral oophorectomy, hysterectomy, or have had bilateral tubal ligation \>6 weeks prior to screening. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with DT2216, breastfeeding should be discontinued if the mother is treated with DT2216. These potential risks may also apply to other agents used in this study; specifically, paclitaxel has known embryo- and fetotoxicity.