A Study of DT2216 in Relapsed/Refractory Malignancies

NCT04886622 | Completed Phase 1 FDA Drug

• 1 other identifier: DT2216-001
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 3

Brief Summary

A Phase 1, Open-Label, Dose Escalation, and Cohort Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK) and Clinical Activity of DT2216, an Antiapoptotic Protein Targeted Degradation Compound, in Subjects with Relapsed or Refractory Malignancies

Conditions

Solid Tumor; Hematologic Malignancy

Outcome Measures

Primary Outcomes (3)

• The number of subjects with adverse events based on the Common Terminology Criteria for Adverse Evens (CTCAE) v5.0 following treatment with DT2216.

  The incidence of adverse events will be the number of subjects with an adverse event divided by the total number subjects.

  28 days

• The number of subjects with adverse events of different grades based on the CTCAE v5.0

  The severity will be based on the grading of adverse events as described in the CTCAE v5.0

  28 days

• The number of subjects with dose limiting toxicity (DLT) of DT2216.

  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

  28 days

Secondary Outcomes (6)

• The measurement of Cmax of DT2216 following intravenous administration

  28 days

• The measurement of the half-life of DT2216 following intravenous administartion

  28 days

• The measurement of the clearance of DT2216 following intravenous administration.

  28 days

• The measurement of levels of BCL-XL in peripheral blood mononuclear cells

  28 days

• The measurement of platelet counts following administration of DT2216

  28 days

Study Arms (1)

DT2216

EXPERIMENTAL

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.

Drug: DT2216

Interventions

DT2216 DRUG

DT2216 will be administered by intravenous infusion

DT2216

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults aged 18 years or older on the day of signing informed consent.
• Provide written informed consent for the trial, including willingness to comply with all study related requirements.
• Histologically or cytologically confirmed solid tumor. Subjects with more than 1 primary malignancy may be considered upon review with the Sponsor's Medical Monitor
• Evidence of disease progression or inadequate response on the last regimen as assessed by the Investigator.
• Has exhausted all curative options or has a contraindication to approved therapies or generally recognized standard-of-care measures for the subject's cancer.
• Presence of measurable disease as assessed by the Investigator per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Has adequate organ functions as defined by the following laboratory parameters at baseline (laboratory parameters outside of these ranges that are deemed clinically insignificant should be discussed with the Medical Monitor): (a) Absolute neutrophil count ≥1.5 x 109/L; (b) hemoglobin ≥9 g/dL; (c) platelet count ≥100,000/mm3; (d) aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x upper limit of normal (ULN); (e) total bilirubin ≤ 1.5 x institutional ULN (exception: subjects with known Gilbert's syndrome and total bilirubin ≤3.0 x ULN at screening or anytime during the prior 6 months are eligible); (f) c) adequate renal function defined as calculated creatinine clearance \>60 mL/min using the Cockcroft-Gault Method (Appendix 3); (g) acceptable coagulation parameters including international normalized ratio (INR) \<1.5 and partial thromboplastin time (PTT) ≤ institutional ULN; (h) serum albumin ≥3.0 g/dL.
• Left ventricular ejection fraction of ≥50% as assessed by echocardiogram or multi-gated acquisition (MUGA) scan.
• Adequate washout from the following prior to first dose of study therapy: Palliative radiation ≥ 2 weeks; chemotherapy or targeted therapy ≥ 3 weeks or 5 half-lives; biologic therapy ≥ 4 weeks.
• Resolution to Grade ≤1 by the National Cancer Institute CTCAE, Version 5.0 (NCI-CTCAE v 5.0) of all clinically significant toxic effects of prior therapies.
• Female subjects: A female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: (a) Not a woman of childbearing potential (WOCBP); (b) WOCBP who agrees to follow the contraceptive guidance during the study treatment period and for at least 120 days after the last dose of study treatment.
• Female subject of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving any dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Male subject is eligible to participate if he agrees to follow the acceptable contraceptive guidance during the study treatment period and for at least 120 days after the last dose of study treatment.

You may not qualify if:

• Subjects are eligible to be included in the study only if all of the following criteria are met:
• Adults aged 18 years or older on the day of signing informed consent.
• Provide written informed consent for the trial, including willingness to comply with all study related requirements.
• Histologically or cytologically confirmed solid tumor. Subjects with more than 1 primary malignancy may be considered upon review with the Sponsor's Medical Monitor.
• Evidence of disease progression or inadequate response on the last regimen as assessed by the Investigator.
• Has exhausted all curative options or has a contraindication to approved therapies or generally recognized standard-of-care measures for the subject's cancer.
• Presence of measurable disease as assessed by the Investigator per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Has adequate organ functions as defined by the following laboratory parameters at baseline (laboratory parameters outside of these ranges that are deemed clinically insignificant should be discussed with the Medical Monitor): (a) Absolute neutrophil count ≥1.5 x 109/L; (b) hemoglobin ≥9 g/dL; (c) platelet count ≥100,000/mm3; (d) aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x upper limit of normal (ULN); (e) total bilirubin ≤ 1.5 x institutional ULN (exception: subjects with known Gilbert's syndrome and total bilirubin ≤3.0 x ULN at screening or anytime during the prior 6 months are eligible); (f) c) adequate renal function defined as calculated creatinine clearance \>60 mL/min using the Cockcroft-Gault Method (Appendix 3); (g) acceptable coagulation parameters including international normalized ratio (INR) \<1.5 and partial thromboplastin time (PTT) ≤ institutional ULN; (h) serum albumin ≥3.0 g/dL.
• Left ventricular ejection fraction of ≥50% as assessed by echocardiogram or MUGA scan.
• Adequate washout from the following prior to first dose of study therapy: Palliative radiation ≥ 2 weeks; chemotherapy or targeted therapy ≥ 3 weeks or 5 half-lives; biologic therapy ≥ 4 weeks.
• Resolution to Grade ≤1 by the National Cancer Institute CTCAE, Version 5.0 (NCI-CTCAE v 5.0) of all clinically significant toxic effects of prior therapies.
• Female subjects: A female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: (a) Not a woman of childbearing potential (WOCBP); (b) WOCBP who agrees to follow the contraceptive guidance during the study treatment period and for at least 120 days after the last dose of study treatment.
• Female subject of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving any dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Male subject is eligible to participate if he agrees to follow the acceptable contraceptive guidance during the study treatment period and for at least 120 days after the last dose of study treatment.

Sponsors & Collaborators

• Dialectic Therapeutics, Inc: lead

Study Sites (3)

Northwestern University

Chicago, Illinois, 60611, United States

Location

Mary Crowley Cancer Research

Dallas, Texas, 75230, United States

Location

Mays Cancer Center

San Antonio, Texas, 78222, United States

Location

Related Publications (2)

• Khan S, Zhang X, Lv D, Zhang Q, He Y, Zhang P, Liu X, Thummuri D, Yuan Y, Wiegand JS, Pei J, Zhang W, Sharma A, McCurdy CR, Kuruvilla VM, Baran N, Ferrando AA, Kim YM, Rogojina A, Houghton PJ, Huang G, Hromas R, Konopleva M, Zheng G, Zhou D. A selective BCL-XL PROTAC degrader achieves safe and potent antitumor activity. Nat Med. 2019 Dec;25(12):1938-1947. doi: 10.1038/s41591-019-0668-z. Epub 2019 Dec 2.

  PMID: 31792461 BACKGROUND

• Mahadevan D, Barve M, Mahalingam D, Parekh J, Kurman M, Strauss J, Tremaine L, Hromas R, Sills J, McCulloch J, Harkey J, Suberg S, Zimmerman L, Zheng G, Zhou D. First in human phase 1 study of DT2216, a selective BCL-xL degrader, in patients with relapsed/refractory solid malignancies. J Hematol Oncol. 2025 Nov 12;18(1):98. doi: 10.1186/s13045-025-01753-8.

  PMID: 41225624 DERIVED

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

DT2216

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Michael Kurman, MD

  Dialectic Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2021
• First Posted: May 14, 2021
• Study Start: August 25, 2021
• Primary Completion: June 30, 2024
• Study Completion: June 30, 2024
• Last Updated: April 16, 2025

Record last verified: 2024-06

Locations

US (3)