A Clinical Study of ONCT-808 in Subjects With Relapsed or Refractory B-Cell Malignancies
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| ClinicalTrials.gov Identifier: NCT05588440 |
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Recruitment Status :
Recruiting
First Posted : October 20, 2022
Last Update Posted : November 30, 2023
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Relapsed/Refractory Aggressive B-Cell Malignancies | Biological: ONCT-808 Drug: Bridging Therapy | Phase 1 Phase 2 |
Study ONCT-808-101 is a Phase 1/2, single-arm, open-label, multi-center study to evaluate the safety and tolerability, pharmacokinetics, and anti-tumor activity of ONCT-808 in subjects with aggressive B cell lymphoma (BCL), including large B-cell lymphoma (LBCL) and mantle cell lymphoma (MCL). The study will be separated into two distinct phases designated as Phase 1 and Phase 2.
After the safety and tolerability of ONCT-808 have been assessed to select the recommended Phase 2 dose (RP2D) in Phase 1, Phase 2 will commence to further validate the dose and evaluate the safety and efficacy of ONCT-808. In Phase 2, subjects with LBCL or MCL will be enrolled into 2 separate dose expansion cohorts.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 57 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Sequential Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Phase 1/2 Multi-Center Study to Evaluate the Safety and Efficacy of ONCT-808 in Adult Subjects With Relapsed or Refractory Aggressive B-Cell Malignancies |
| Actual Study Start Date : | May 9, 2023 |
| Estimated Primary Completion Date : | December 2026 |
| Estimated Study Completion Date : | December 2037 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Phase 1: Dose Escalation
Patients will receive a conditioning regimen of cyclophosphamide and fludarabine intravenously (IV) followed by ONCT-808 IV infusion escalated sequentially with a target dose consistent with the dose required by cohort being enrolled to determine Phase 2 dose (RP2d) regimen(s). Participants may receive bridging therapy that is appropriate to the subject's disease and treatment history if clinically indicated to maintain disease stability.
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Biological: ONCT-808
A single infusion of ONCT-808 autologous CAR-T cell infusion will be administered intravenously Phase 1: Dose Escalation with bridging therapy as needed Phase 2: Patients with LBCL or MCL will be enrolled into two separate dose expansion cohorts. Drug: Bridging Therapy Bridging therapy can be oral chemotherapy or IV radiotherapy/chemotherapy per institution's guidelines |
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Experimental: Phase 2: Dose Expansion
Patients with LBCL or MCL will receive ONCT-808 for each RP2D regimen determined in Phase 1.
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Biological: ONCT-808
A single infusion of ONCT-808 autologous CAR-T cell infusion will be administered intravenously Phase 1: Dose Escalation with bridging therapy as needed Phase 2: Patients with LBCL or MCL will be enrolled into two separate dose expansion cohorts. Drug: Bridging Therapy Bridging therapy can be oral chemotherapy or IV radiotherapy/chemotherapy per institution's guidelines |
- To evaluate the incidence, severity, and relationship of Dose Limiting Toxicities (DLT) [ Time Frame: 28 days after last dose of ONCT-808 ]
- To evaluate the incidence, severity, and relationship of Treatment Emergent Adverse Events (TEAE) [ Time Frame: Up to 24 months ]
- To select a RP2D of ONCT-808 [ Time Frame: Up to 24 months ]
- To evaluate the Overall Response Rate (ORR) of ONCT-808 [ Time Frame: Up to 48 months ]Evaluate ORR rate according to Lugano 2014 (Cheson, 2014)
- To evaluate the Complete Response (CR) of ONCT-808 [ Time Frame: Up to 48 months ]Evaluate CR rate according to Lugano 2014 (Cheson, 2014)
- To evaluate the Duration of Response (DOR) of ONCT-808 [ Time Frame: Up to 48 months ]Evaluate DOR according to Lugano 2014 (Cheson, 2014)
- Pharmacokinetics of ONCT-808 [ Time Frame: Up to 15 years ]Evaluate the expansion and persistence of ROR1 CAR-positive T cells in peripheral blood
- Safety and Tolerability of ONCT-808 [ Time Frame: Up to 15 years ]Objective to further characterize the safety profile, including incidence, severity, and relationship of TEAEs
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Key Inclusion Criteria:
- Over 18 years old
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Histologically confirmed aggressive B-cell NHL, including:
- MCL, with diagnosis confirmed by cyclin D1 overexpression or evidence of t (11;14) translocation
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LBCL, including:
- DLBCL NOS
- Primary mediastinal LBCL
- High-grade BCL
- DLBCL arising from follicular lymphoma
- Follicular lymphoma grade 3B
- Richter's syndrome
- Availability of archival tissue for immunohistology, or willing to undergo baseline biopsy if not available
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R/R with no available therapy. Subject must have:
- Received prior systemic therapy that has included an alkylating agent, anthracycline, and an anti-CD20 mAb
- Received and progressed after autologous hematopoietic stem cell transplant (HSCT) or is ineligible for or has refused to receive HSCT
- Received prior approved CD19 CAR T-cell therapy or is ineligible for or has refused CD19 CAR-T
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Minimum washout period between previous systemic therapy and leukapheresis includes:
- Chemotherapy: at least 14 days or 5 half-lives, whichever is shorter
- Autologous HSCT: at least 3 months
- CD19 CAR T-cell therapy: at least 6 months
- ≥1 measurable lesion per Lugano criteria (Cheson, 2014)
- Subject has Fluorodeoxyglucose (FDG)-avid disease.
- Subject has an ECOG performance status of 0 or 1.
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Subject has adequate organ function:
- ALC ≥100/uL
- ANC ≥1000/uL (≥500/uL if due to lymphoma; growth factors allowed)
- Hgb ≥8 g/dL (transfusion allowed)
- Platelets ≥75,000/uL (≥50,000/uL if due to lymphoma; transfusion allowed)
- CrCL ≥50 ml/min; AST/ALT ≤2.5x ULN, T. bili ≤1.5 mg/dl (except Gilbert's)
- EF ≥50% by ECHO/MUGA; NCS ECG, NCS pleural effusion; O2 sat >92%
- Subject has an estimated life expectancy of >12 weeks
Key Exclusion Criteria:
- Prior ROR1-targeted therapy
- Current or anticipated systemic immunosuppressive therapy (e.g., prednisone >5 mg) from LD chemo until Day 28 post ONCT-808 dosing
- If receiving anticoagulation therapy, subject is unable to hold therapy for 3 days prior and 28 days following ONCT-808 administration
- Known CNS involvement by malignancy within 6 months
- H/o or current CNS disorder (e.g., seizure, CVA, dementia, cerebellar disease, cerebral edema, posterior reversible encephalopathy syndrome or any autoimmune disease with CNS involvement) within 6 months of study entry
- Clinically significant cardiovascular disease (e.g., MI, UA, CABG, or CHF grade ≥2 NYHA within 12 months of planned ONCT-808 dosing) or serious arrhythmia requiring medication
- Evidence of HIV infection or active HBV, HCV
- Systemic fungal infection requiring medication in the last 12 months
- H/o Covid-19 infection with residual lung infiltrate/fibrosis
- H/o other malignancy except non-melanoma skin cancer or carcinoma in situ not in remission for ≥2 years
- H/o autoimmune disease resulting in end organ injury or require systemic immunosuppression within last 2 years
- H/o allogeneic HSCT or organ transplant
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): NCT05588440
| Contact: Ariadne Jerue | 858-761-8062 | ajerue@oncternal.com |
| United States, California | |
| City of Hope National Medical Center | Recruiting |
| Duarte, California, United States, 91010 | |
| Contact: MD | |
| United States, Massachusetts | |
| Massachusetts General Hospital | Recruiting |
| Boston, Massachusetts, United States, 02114 | |
| Contact: MD | |
| Dana Farber Cancer Institute | Recruiting |
| Boston, Massachusetts, United States, 02215 | |
| Contact: MD | |
| United States, Texas | |
| The University of Texas MD Anderson Cancer Center | Recruiting |
| Houston, Texas, United States, 77030 | |
| Contact: MD | |
| Principal Investigator: | Michael Wang | MD Anderson | |
| Principal Investigator: | Matthew Wei | City of Hope Medical Center |
| Responsible Party: | Oncternal Therapeutics, Inc |
| ClinicalTrials.gov Identifier: | NCT05588440 |
| Other Study ID Numbers: |
ONCT-808-101 |
| First Posted: | October 20, 2022 Key Record Dates |
| Last Update Posted: | November 30, 2023 |
| Last Verified: | November 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Undecided |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Lymphoma Lymphoma, B-Cell Lymphoma, Large B-Cell, Diffuse Lymphoma, Mantle Cell Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders |
Immune System Diseases Lymphoma, Non-Hodgkin ROR1 CAR-T cell therapy Autologous CAR-T cell therapy Adoptive cellular therapy Cellular immunotherapy |
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Neoplasms Aggression Aberrant Motor Behavior in Dementia Behavioral Symptoms |