Testing the Addition of an Anti-cancer Drug, DT2216, to the Usual Chemotherapy Treatment for Relapsed or Refractory Solid Tumors and Fibrolamellar Carcinoma

NCT06620302 | Recruiting Phase 1 FDA Drug

• 3 other identifiers: PEPN2411NCI-2024-06357UM1CA228823
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 21

Brief Summary

This phase I/II trial tests the safety, side effects and best dose of DT2216 in combination with irinotecan and how well it works in treating children, adolescents and young adults with solid tumors and fibrolamellar cancer that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). DT2216 is an anti-apoptotic protein B-cell lymphoma-extra large targeted protein degrader. It may stop the growth of tumor cells by blocking Bcl-xL, a protein needed for tumor cell survival. Irinotecan is in a class of antineoplastic medications called topoisomerase I inhibitors. It blocks a certain enzyme needed for cell division and deoxyribonucleic acid repair and may kill tumor cells. Giving DT2216 in combination with irinotecan may be safe, tolerable, and/or effective in treating children, adolescents and young adults with relapsed or refractory solid tumors or fibrolamellar cancer.

Conditions

Recurrent Childhood Malignant Solid Neoplasm; Childhood Fibrolamellar Carcinoma; Recurrent Childhood Fibrolamellar Carcinoma; Recurrent Fibrolamellar Carcinoma; Recurrent Malignant Solid Neoplasm; Refractory Childhood Fibrolamellar Carcinoma; Refractory Childhood Malignant Solid Neoplasm; Refractory Fibrolamellar Carcinoma; Refractory Malignant Solid Neoplasm

Outcome Measures

Primary Outcomes (10)

• Incidence of adverse events (AEs)

  AEs will be assessed and graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0. A descriptive summary of all toxicities will be reported.

  Up to 30 days after last dose of study drug

• Dose-limiting toxicity (DLT)

  AEs will be assessed and graded using NCI CTCAE v5.0. A descriptive summary of all toxicities will be reported.

  Up to 21 days

• Maximum tolerated dose (MTD)/ recommended phase 2 dose

  MTD will be defined as the maximum dose at which fewer than one-third of patients experience DLT during cycle 1 of therapy.

  Up to 21 days

• Area under the dose concentration curve of DT2216

  Median (minimum \[min\], maximum \[max\]) area under the dose concentration curve of DT2216 during cycle 1 assessed pre-dose, 5, 30, 60, 180, and 420 minutes post-dose.

  Up to 7 hours

• Clearance of DT2216

  Median (min, max) clearance of DT2216 during cycle 1 assessed pre-dose, 5, 30, 60, 180, and 420 minutes post-dose.

  Up to 7 hours

• Half-life of DT2216

  Median (min, max) Half-life of DT2216 during cycle 1 assessed pre-dose, 5, 30, 60, 180, and 420 minutes post-dose.

  Up to 7 hours

• Area under the dose concentration curve of irinotecan

  Median (min, max) area under the dose concentration curve of irinotecan during cycle 1 assessed pre-dose, 5, 30, 60, 180, and 420 minutes post-dose.

  Up to 7 hours

• Clearance of irinotecan

  Median (min, max) clearance of irinotecan during cycle 1 assessed pre-dose, 5, 30, 60, 180, and 420 minutes post-dose.

  Up to 7 hours

• Half-life of irinotecan

  Median (min, max) Half-life of irinotecan during cycle 1 assessed pre-dose, 5, 30, 60, 180, and 420 minutes post-dose.

  Up to 7 hours

• Overall response rate (ORR)

  ORR will be recorded from the start of the treatment until disease progression or recurrence. ORR of partial response, complete response or stable disease will be assessed according to Response Evaluation Criteria in Solid Tumors Criteria and will be reported descriptively.

  At start of treatment until disease progression or recurrence up to 60 months

Secondary Outcomes (1)

• Pharmacodynamic activity

  Up to end of cycle 5 (105 days)

Other Outcomes (5)

• Correlation of peripheral blood levels of the DNAJB1-PRKACA chimera

  Up to 60 months

• Vitamin B12 levels

  Up to 60 months

• Genomic markers panel

  Up to 60 months

Study Arms (1)

Treatment (DT2216, irinotecan)

EXPERIMENTAL

Patients receive DT2216 IV over 30 minutes on days 1, 4, 8, 11, 15, and 18 of each cycle and irinotecan IV over 90 minutes on days 2-6 of cycle 1, and on days 1-5 of remaining cycles. Cycles repeat every 21 days for up to 35 cycles (24 months) in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection throughout the trial.

Biological: Bcl-XL Proteolysis Targeting Chimera DT2216; Procedure: Biospecimen Collection; Drug: Irinotecan

Interventions

Irinotecan DRUG

Given IV

Treatment (DT2216, irinotecan)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (DT2216, irinotecan)

Bcl-XL Proteolysis Targeting Chimera DT2216 BIOLOGICAL

Given IV

Also known as: Antiapoptotic Protein Targeted Degrader DT2216, APTaD DT2216, Bcl-XL Degrader DT2216, Bcl-XL PROTAC DT2216, BCL-XL-specific PROTAC DT2216, DT 2216, DT-2216, DT2216, PROTAC Bcl-XL Deagrader DT2216, PROTAC DT2216, Proteolysis-targeting Chimera Protein Degrader DT2216

Treatment (DT2216, irinotecan)

Eligibility Criteria

• Age: 1 Year - 39 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• PHASE 1: Patients between ≥ 1 year and ≤ 21 years of age at the time of study enrollment
• PHASE 2: Patients between ≥ 1 year and ≤ 39 years of age at the time of study enrollment
• PHASE 1: Patients with recurrent/refractory solid tumors excluding primary central nervous system tumors
• PHASE 2: Patients with (FLC), which must include genomic confirmation of the DNAJB1:PRKACA fusion performed at a Clinical Laboratory Improvement Act (CLIA)-certified laboratory
• PHASE 1: Patients must have either measurable or evaluable disease
• PHASE 2: Patients must have measurable disease
• PHASE 1: Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
• PHASE 2: Patients must have FLC which is recurrent/refractory to at least one line of prior systemic therapy
• Patients with FLC that is unresectable at initial diagnosis but is not recurrent/refractory to at least one prior line of systemic therapy nor metastatic are NOT eligible for either phase 1 or phase 2
• Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients \> 16 years of age and Lansky for patients ≤ 16 years of age
• Patients must have fully recovered (grade \< 2) from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, eg, blood count criteria, the patient is considered to have recovered adequately
• Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive: See Developmental Therapeutics (DVL) homepage on the Children's Oncology Group (COG) members site for commercial and investigational agent classifications. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment
• Solid tumor patients: ≥ 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea). Please refer to the table of myelosuppressive/anticancer agents on the COG website
• Anti-cancer agents not known to be myelosuppressive (eg, not associated with reduced platelet or absolute neutrophil count \[ANC\] counts): ≥ 7 days after the last dose of agent. See the DVL homepage on the COG Members site for commercial and investigational agent classifications. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment
• Antibodies: ≥ 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade ≤ 1

You may not qualify if:

• Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies, OR because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method (eg, male or female condom) for the duration of the study. Abstinence is an acceptable method of birth control. Patients who could become pregnant should use highly effective contraception during therapy and for 6 months after the last irinotecan dose or 120 days after the last dose of DT2216, whichever is longer. Patients with partners who could become pregnant should use condoms during therapy and for 3 months after the last dose irinotecan or 120 days after the last dose of DT2216, whichever is longer
• Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible. If used to modify immune adverse events related to prior therapy, ≥ 14 days must have elapsed since last dose of corticosteroid
• Patients who are currently receiving another investigational drug are not eligible
• Patients who are currently receiving other anti-cancer agents are not eligible
• Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
• Patients who have received drugs that are strong inducers or inhibitors of CYP3A4 within 14 days prior to study enrollment are not eligible
• Patients with lymphoma are excluded
• Patients who have an uncontrolled infection are not eligible
• Patients with grade ≥ 2 diarrhea at baseline are not eligible
• Patients who have received a prior solid organ transplantation are not eligible
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
• Dedicated central nervous system (CNS) imaging is not required but patients with current active CNS metastasis whether symptomatic or discovered incidentally without clinical symptoms, are not eligible
• Patients with grade \> 2 corrected QT interval (i.e. electrocardiogram \[EKG\] showing corrected QT interval \[QTc\] \> 480 ms) at baseline are not eligible
• Surgical procedure
• Central line placement, open or core needle biopsy of sites other than liver: \< 2 days prior to enrollment.

Sponsors & Collaborators

• Children's Oncology Group: lead

Study Sites (21)

Children's Hospital of Alabama

Birmingham, Alabama, 35233, United States

RECRUITING

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

RECRUITING

Children's Hospital of Orange County

Orange, California, 92868, United States

RECRUITING

UCSF Medical Center-Mission Bay

San Francisco, California, 94158, United States

RECRUITING

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

RECRUITING

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

RECRUITING

Children's Healthcare of Atlanta - Arthur M Blank Hospital

Atlanta, Georgia, 30329, United States

RECRUITING

Lurie Children's Hospital-Chicago

Chicago, Illinois, 60611, United States

RECRUITING

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

C S Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

RECRUITING

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

RECRUITING

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, 10032, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

RECRUITING

Saint Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

RECRUITING

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Seattle Children's Hospital

Seattle, Washington, 98105, United States

RECRUITING

MeSH Terms

Conditions

Fibrolamellar hepatocellular carcinoma

Interventions

DT2216; Specimen Handling; Irinotecan

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Camptothecin; Alkaloids; Heterocyclic Compounds

Study Officials

• Michael V Ortiz

  Pediatric Early Phase Clinical Trial Network

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: September 26, 2024
• First Posted: October 1, 2024
• Study Start: June 12, 2025
• Primary Completion (Estimated): December 30, 2031
• Study Completion (Estimated): December 30, 2031
• Last Updated: May 5, 2026

Record last verified: 2025-07

Locations

US (21)