A Study of DT2216 in Relapsed/Refractory Malignancies
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|ClinicalTrials.gov Identifier: NCT04886622|
Recruitment Status : Recruiting
First Posted : May 14, 2021
Last Update Posted : April 7, 2022
|Condition or disease||Intervention/treatment||Phase|
|Solid Tumor Hematologic Malignancy||Drug: DT2216||Phase 1|
This study is an open-label, first-in-human, dose escalation study in subjects with histologically or cytologically confirmed advanced or metastatic malignancies who are no longer responsive to approved or accepted standard-of-care interventions. The study will consist of a dose escalation phase followed by confirmation of the recommended phase 2 dose (RP2D).
Potentially eligible subjects will undergo screening evaluations (up to 28 days prior to study therapy) and those who meet all protocol-defined eligibility criteria will be enrolled into the study. Subjects who fail screening may be re-screened one time following correction or mitigation of the condition that caused the screen failure; there is no time limit on when a subject may be re-screened. Enrolled subjects will receive a single intravenous (IV) infusion of study drug on Days 1 and 4 weekly for at least 4 weeks, with each cycle consisting of 28 days. Treatment duration for an individual subject may continue for a maximum of 1 year, until disease progression, unacceptable toxicity, subject withdrawal, Investigator's decision for a change in treatment strategy for the individual subject, or death. Longer therapy may be considered for individual subjects upon consultation with the Sponsor's Medical Monitor and overall assessment of benefit:risk. Subjects will be followed for safety for 28 days following the administration of the last study treatment.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||24 participants|
|Intervention Model:||Sequential Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1, Dose Escalation and Cohort Expansion Study to Evaluate the Safety, Pharmacokinetics and Clinical Activity of DT2216, an Antiapoptotic Protein Targeted Degradation Compound, in Patients With Relapsed/Refractory Malignancies|
|Actual Study Start Date :||August 25, 2021|
|Estimated Primary Completion Date :||October 31, 2022|
|Estimated Study Completion Date :||April 15, 2023|
DT2216 will be administered by intravenous infusion over 30 minutes twice weekly on a continuous basis. Each treatment cycle will be 28 days in duration. The starting dose of DT2216 will be 0.04 mg/kg and will escalate by 100% increments for the first 5 treatment groups. Thereafter, if additional dose escalations are required, escalation will follow a modified Fibonacci scheme. Treatment may continue for up to 1 year.
DT2216 will be administered by intravenous infusion
- The number of subjects with adverse events based on the Common Terminology Criteria for Adverse Evens (CTCAE) v5.0 following treatment with DT2216. [ Time Frame: 28 days ]The incidence of adverse events will be the number of subjects with an adverse event divided by the total number subjects.
- The number of subjects with adverse events of different grades based on the CTCAE v5.0 [ Time Frame: 28 days ]The severity will be based on the grading of adverse events as described in the CTCAE v5.0
- The number of subjects with dose limiting toxicity (DLT) of DT2216. [ Time Frame: 28 days ]
DLT's will be defined by any of the following:
Any Grade 5 toxicity on the CTCAE CTCAE v5.0 Grade 4 thrombocytopenia or Grade 3 thrombocytopenia associated with clinically significant hemorrhage CTCAE Grade 4 neutropenia lasting >7 days Febrile Neutropenia, defined as absolute neutrophil count (ANC) <1000/mm3 with a single temperature of >38.3°C (101°F) or a sustained temperature of >38°C (100.4°F) for >1 hour Grade 3 thrombocytopenia that is clinically uncomplicated and lasting ≥7 days. CTCAE Grade 4 non-hematologic toxicity of any duration CTCAE Grade 3 non-hematologic toxicity, except nausea, vomiting and/or diarrhea lasting ≤3 days or laboratory abnormalities that return to baseline within ≤3 days with or without medical intervention Changes in liver enzymes consistent with Hy's law indicative of drug-induced hepatocellular injury
- The measurement of Cmax of DT2216 following intravenous administration [ Time Frame: 28 days ]The Cmax will be based on blood levels following intravenous administrration of DT2216.
- The measurement of the half-life of DT2216 following intravenous administartion [ Time Frame: 28 days ]The half-life will be based on blood levels of DT2216 following intravenous administration.
- The measurement of the clearance of DT2216 following intravenous administration. [ Time Frame: 28 days ]The clearance of DT2216 will be based on blood levels of DT2216 following intravenous administration
- The measurement of levels of BCL-XL in peripheral blood mononuclear cells [ Time Frame: 28 days ]Levels of BCL-XL will be measured in peripheral blood mononuclear cells
- The measurement of platelet counts following administration of DT2216 [ Time Frame: 28 days ]Platelet counts will be determined at various time points after administration of DT2216
- The number of subjects who have oncological responses to DT2216 based on the RECIST 1.1 criteria. [ Time Frame: One year ]The response rate to DT2216 will be determined at various time points following administration of DT2216 based on the Response Evaluation Criteria in Solid Tumors 1.1.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04886622
|Contact: Michael Kurman, MD||201-410-3205||Mkurman@pharmadvisors.com|
|United States, Illinois|
|Chicago, Illinois, United States, 60611|
|Contact: Zainub Ashrafi 312-695-6935 email@example.com|
|Principal Investigator: Devalingam Mahalingam, MD|
|United States, Texas|
|Mary Crowley Cancer Research||Recruiting|
|Dallas, Texas, United States, 75230|
|Contact: Minal Barve 972-566-3000 referral@MaryCrowley.com|
|Principal Investigator: Minai Barve, MD|
|Mays Cancer Center||Recruiting|
|San Antonio, Texas, United States, 78222|
|Contact: Lisa Creighton 210-450-1366 Creighton@uthscsa.edu|
|Principal Investigator: Daruka Mahadevan, MD|
|Study Director:||Michael Kurman, MD||Dialectic Therapeutics|