A Clinical Study of ONCT-808 in Subjects With Relapsed or Refractory B-Cell Malignancies

NCT05588440 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: ONCT-808-101
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 4

Brief Summary

This is a Phase 1/2 study to investigate the safety and efficacy of the CAR-T therapy, ONCT-808, in patients with relapsed/refractory (R/R) aggressive B cell malignancies.

Conditions

Relapsed/Refractory Aggressive B-Cell Malignancies

Keywords

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

Outcome Measures

Primary Outcomes (1)

• To Evaluate the Incidence of Dose Limiting Toxicities (DLT)

  This is based on subject treated with ONCT-808. ONCT-808 1x10\^6 CAR T cells/kg: n=3 ONCT-808 3x10\^6 CAR T cells/kg: n=1 ONCT-808 0.3x10\^6 CAR T cells/kg: n=2

  Up to 28 days after the one-time infusion of ONCT-808

Secondary Outcomes (1)

• Best Metabolic Response Rate Post-Baseline

  up to 1 year after the one-time infusion of ONCT-808

Study Arms (2)

Phase 1: Dose Escalation

EXPERIMENTAL

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.

Biological: ONCT-808; Drug: Bridging Therapy

Phase 2: Dose Expansion

EXPERIMENTAL

Patients with LBCL or MCL will receive ONCT-808 for each RP2D regimen determined in Phase 1.

Biological: ONCT-808; Drug: Bridging Therapy

Interventions

ONCT-808 BIOLOGICAL

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.

Phase 1: Dose Escalation; Phase 2: Dose Expansion

Bridging Therapy DRUG

Bridging therapy can be oral chemotherapy or IV radiotherapy/chemotherapy per institution's guidelines

Phase 1: Dose Escalation; Phase 2: Dose Expansion

Eligibility Criteria

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

You may qualify if:

• Over 18 years old
• Histologically confirmed aggressive B-cell NHL, including:
• MCL, with diagnosis confirmed by cyclin D1 overexpression or evidence of t (11;14) translocation
• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Oncternal Therapeutics, Inc: lead

Study Sites (4)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Recurrence; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Mantle-Cell; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms by Histologic Type; Neoplasms; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Mary Breitmeyer
• Organization: Oncternal Therapeutics

mbreitmeyer@oncternal.com

760-703-2802

Study Officials

• Michael Wang

  MD Anderson

  PRINCIPAL INVESTIGATOR

• Matthew Wei

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: September 23, 2022
• First Posted: October 20, 2022
• Study Start: May 9, 2023
• Primary Completion: September 12, 2024
• Study Completion: September 12, 2024
• Last Updated: December 5, 2024
• Results First Posted: December 5, 2024

Record last verified: 2024-11

Locations

US (4)