ONCT-534 / Oncternal Therap - LARVOL DELTA

Discovery of Androgen Metabolism Enhancing Androgen Receptor Antagonists for the Treatment of Castration-Resistant prostate Cancer (EORTC-NCI-AACR 2024) - "To provide sustained treatment options, next-generation ARSIs with unique mechanisms of action, including our AR N terminus domain (NTD) binding degrader (SARD), ONCT-534, and PROTAC ARV-110 are in clinical development...Transcriptomic analysis with a combination of 19B and enzalutamide showed regulation of pathways that are distinct from that of enzalutamide. The results indicate that UGT2B enzyme expression and function are critical for the efficacy of AR antagonists. We have also discovered a new class of AR antagonist that sustainedly induces UGT2Bs and synergizes with clinical AR antagonists to inhibit PCa and CRPC growth."

Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • ARSI

Oncternal Therapeutics Announces Updated Safety and Efficacy Data for Phase 1/2 Study of ONCT-534 for the Treatment of R/R Metastatic Castration-Resistant Prostate Cancer (GlobeNewswire) - P1/2 | N=21 | NCT05917470 | Sponsor: Oncternal Therapeutics, Inc | "Based on initial pharmacokinetic results, two additional dosing cohorts with twice daily (BID) oral dosing of ONCT-534 had been incorporated in the Phase 1/2 study ONCT-534-101 (NCT05917470). Overall, fifteen patients received ONCT-534 once daily (QD) in six dosing cohorts and six patients received ONCT-534 BID in two dosing cohorts. Based on a data cut off of September 30, 2024, the BID dosing schedule was well tolerated, with no related Grade 3 or higher toxicities. One patient, who experienced a rising PSA on ONCT-534 at 160 mg BID, had a subsequent 50% reduction in PSA after four weeks of ONCT-534 at 300 mg BID, and at the same time the CAT Scan showed a 16% reduction in target lesions compared to baseline....CTC analysis also showed that some patients who did not respond to ONCT-534 had prostate cancer that had developed neuroendocrine features, which are associated with AR independent disease."

P1/2 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Oncternal Therapeutics Announces Termination of its Clinical Studies and Exploration of Strategic Alternatives (GlobeNewswire) - P1 | N=57 | NCT05588440 | Sponsor: Oncternal Therapeutics Inc. | "Oncternal Therapeutics...announced its decision to discontinue its clinical trials evaluating...ONCT-808, its ROR1-targeting autologous CAR T program for the treatment of patients with aggressive B-cell lymphoma, and to explore strategic alternatives...The results with ONCT-808 at an interim Phase 1 analysis showed anti-tumor activity at every dose tested, including a complete metabolic response lasting eight months and long-term persistence of the CAR-T cells, with expected treatment emergent adverse events for a CAR-T therapy, and one death due to complications of shock at the highest dose tested...Company will discontinue all product development activities....'In light of these data and the challenging financing environment, we intend to explore strategic options with the hope of advancing and realizing value from our pipeline including ONCT-534, ONCT-808, zilovertamab and ONCT-216.'"

Discontinued • P1 data • Pipeline update • Trial termination • Castration-Resistant Prostate Cancer • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Mediastinal B Cell Lymphoma • Metastatic Castration-Resistant Prostate Cancer • Non-Hodgkin’s Lymphoma • Oncology • Prostate Cancer • Solid Tumor

ONCT-534-101: A Clinical Study of ONCT-534 in Subjects with Metastatic Castration-resistant Prostate Cancer. (clinicaltrials.gov) - P1/2 | N=21 | Terminated | Sponsor: Oncternal Therapeutics, Inc | N=59 ➔ 21 | Trial completion date: Jan 2028 ➔ Sep 2024 | Recruiting ➔ Terminated | Trial primary completion date: Jan 2028 ➔ Sep 2024; Interim Phase 1 results of ONCT-534 did not show clinically meaningful improvements of disease, including prostate-specific antigen (PSA) levels, in the 20 patients treated in eight dosing cohorts with various doses and schedules of administration.

Enrollment change • Metastases • Trial completion date • Trial primary completion date • Trial termination • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Oncternal Therapeutics Announces Termination of its Clinical Studies and Exploration of Strategic Alternatives (GlobeNewswire) - "Oncternal Therapeutics...announced its decision to discontinue its clinical trials evaluating ONCT-534, its dual action androgen receptor inhibitor for the treatment of patients with metastatic castration resistant cancer...In the current study, interim Phase 1 results of ONCT-534 did not show clinically meaningful improvements...Based on the available clinical data and capital requirements for continued development, the Company has decided to terminate these studies....While this strategic exploration is ongoing, the Company will discontinue all product development activities and will take other steps to reduce costs, including a reduction in its workforce to preserve cash resources."

Discontinued • Trial termination • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Oncternal Therapeutics Provides Business Update and Announces Second Quarter 2024 Financial Results (GlobeNewswire) - "Expected Upcoming Milestones: (i) ONCT-534, our dual-action androgen receptor inhibitor: Initial clinical data in the third quarter of 2024; Additional clinical data readouts in the fourth quarter of 2024; (ii) ONCT-808, our autologous ROR1-targeted CAR T cell therapy: Clinical data update in the fourth quarter of 2024."

P1/2 data • Diffuse Large B Cell Lymphoma • Mantle Cell Lymphoma • Metastatic Castration-Resistant Prostate Cancer

Oncternal Announces Enrollment Completed and Dosing Initiated for Sixth Dose Cohort of Phase 1/2 Study of ONCT-534 for the Treatment of R/R Metastatic Castration-Resistant Prostate Cancer (GlobeNewswire) - "Oncternal Therapeutics, Inc...announced that enrollment has been completed and dosing initiated for the sixth dose cohort of its Phase 1/2 study of ONCT-534 for the treatment of patients with metastatic castration-resistant prostate cancer who are relapsed or refractory to approved androgen receptor pathway inhibitors (ARPI). Patients in the sixth cohort are receiving ONCT-534, the company’s dual-action androgen receptor inhibitor (DAARI), at a dose of 1200 mg taken orally once each day. The decision to proceed to this higher dose level was made by the study’s Safety Review Committee (SRC) after reviewing data from the fifth dose level of 600 mg ONCT-534 daily. An initial update on ONCT-534 safety and efficacy based on prostate–specific antigen (PSA) levels from this study is expected in the third quarter of 2024 and will include data from this 1200 mg dose cohort."

P1/2 data • Trial status • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

A phase 1/2 study of ONCT-534, a dual-action androgen receptor inhibitor (DAARI), in patients with metastatic castration-resistant prostate cancer. (ASCO 2024) - P1/2 | "Cohorts 1 and 2 have been completed without DLT. Enrollment into Cohort 3 began in January 2024 (NCT 05917470)."

Clinical • Metastases • P1/2 data • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Oncternal Announces Enrollment Completed and Dosing Initiated for Fifth Dose Cohort of Phase 1/2 Study of ONCT-534 for the Treatment of R/R Metastatic Castration-Resistant Prostate Cancer (GlobeNewswire) - "Oncternal Therapeutics...announced that enrollment has been completed and dosing initiated for the fifth dose cohort of its Phase 1/2 study of ONCT-534 for the treatment of patients with metastatic castration-resistant prostate cancer who are relapsed or refractory to approved androgen receptor pathway inhibitors (ARPI). Patients in the fifth cohort are receiving ONCT-534, the company’s dual-action androgen receptor inhibitor (DAARI), at a dose of 600 mg taken orally once each day. The decision to proceed to this higher dose level was made by the study’s Safety Review Committee (SRC) after reviewing data from the fourth dose level of 300 mg ONCT-534 daily. An initial update on ONCT-534 safety and efficacy based on prostate-specific antigen (PSA) levels from this study is expected in the third quarter of 2024 and will include data from this 600 mg dose cohort."

DSMB • P1/2 data • Trial status • Metastatic Castration-Resistant Prostate Cancer

Oncternal Announces First Patient Dosed in Fourth Cohort of Phase 1/2 Study of ONCT-534 for the Treatment of R/R Metastatic Castration-Resistant Prostate Cancer (GlobeNewswire) - "Oncternal Therapeutics, Inc...today announced that the first patient has been dosed in the fourth cohort of its Phase 1/2 study of ONCT-534 for the treatment of patients with advanced prostate cancer who are relapsed or refractory to approved androgen receptor pathway inhibitors (ARPI). Patients in the fourth dosing cohort will receive ONCT-534, the company’s dual-action androgen receptor inhibitor (DAARI), at a dose of 300 mg taken orally each day. The decision to proceed to this higher dose level was made by the study’s Safety Review Committee (SRC) after reviewing data from the patients treated to date, including the third dose level of 160 mg ONCT-534 daily....'We look forward to announcing initial efficacy and safety data from the study, which we expect will be at the end of this quarter.'"

DSMB • P1/2 data • Trial status • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Oncternal Participating in Virtual Fireside Chat with Key Opinion Leader on Treatment Landscape & New Treatment Options for Prostate Cancer (GlobeNewswire) - "Oncternal Therapeutics, Inc...announced it will participate in a virtual fireside chat on the Treatment Landscape & New Treatment Options for Prostate Cancer....Dr. Breitmeyer will discuss the development of Oncternal’s novel dual-acting androgen receptor inhibitor, ONCT-534, the ongoing Phase 1/2 clinical trial ONCT-534-101, and the potential positioning of ONCT-534 within the treatment paradigm of advanced prostate cancer."

Clinical • Trial status • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Oncternal Therapeutics Provides Business Update and Announces Fourth Quarter and Full Year 2023 Financial Results (GlobeNewswire) - "Expected Upcoming Milestones: (i) ONCT-534, our dual-action androgen receptor inhibitor: Initial clinical data update in the second quarter of 2024; Additional clinical data readouts in the fourth quarter of 2024; (ii) ONCT-808, our autologous ROR1-targeted CAR T cell therapy: Clinical data update in mid-2024; Additional clinical data readouts in the fourth quarter of 2024."

P1/2 data • Diffuse Large B Cell Lymphoma • Metastatic Castration-Resistant Prostate Cancer • Richter's Syndrome

A phase 1/2 study of ONCT-534, a dual-action androgen receptor inhibitor (DAARI), in patients with metastatic castration-resistant prostate cancer. (ASCO-GU 2024) - P1/2 | "Background: Current therapeutic strategies for metastatic castration-resistant prostate cancer (mCRPC) include treatment with next-generation androgen receptor signaling inhibitors (ARSIs), such as enzalutamide, darolutamide, and apalutamide, which all target the ligand-binding domain (LBD) of the AR, and abiraterone, an androgen biosynthesis inhibitor. The study was opened for enrollment September 2023. Clinical trial information: NCT05917470."

Clinical • Metastases • P1/2 data • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Oncternal Therapeutics Enrolls Patients into the Third Dosing Cohort of its Phase 1/2 Study of ONCT-534 for the Treatment of R/R Metastatic Castration-Resistant Prostate Cancer (GlobeNewswire) - "Oncternal Therapeutics, Inc...today announced that the fourth patient has now been enrolled into its Phase 1/2 study of ONCT-534, its dual-action androgen receptor inhibitor, for the treatment of patients with advanced prostate cancer who are relapsed or refractory to approved androgen receptor pathway inhibitors (ARPI). The last two patients were enrolled into the third dosing cohort, to receive ONCT-534 at a dose of 160 mg taken orally each day. The study utilizes an adaptive Bayesian Optimal Interval (BOIN) design, under which the first two dosing cohorts treated one patient each at 40 mg ONCT-534 per day and 80 mg ONCT-534 per day, respectively. The decision to proceed to dose level 3 was confirmed by the study’s Safety Review Committee (SRC)."

Enrollment status • Trial status • Metastatic Castration-Resistant Prostate Cancer

Oncternal Therapeutics Provides Business Update and Announces Third Quarter 2023 Financial Results (GlobeNewswire) - "ONCT-808, our autologous ROR1-targeted CAR T cell therapy: Initial clinical data available by the end of 2023; Additional clinical data readouts in 2024....ONCT-534, our dual-action androgen receptor inhibitor: Initial clinical data available in the first half of 2024."

P1/2 data • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

Oncternal Therapeutics Adds Matthew Smith, M.D., Ph.D. to its Prostate Cancer Scientific Advisory Board (GlobeNewswire) - "Oncternal Therapeutics, Inc...today announced the addition of Matthew Smith, M.D., Ph.D. to its Prostate Cancer Scientific Advisory Board (SAB). Dr. Smith, along with the other Prostate Cancer SAB members, will help guide Oncternal’s next steps in the clinical development of its novel dual-acting androgen receptor inhibitor (DAARI), ONCT-534, which is currently under investigation in an ongoing Phase 1/2 clinical study, ONCT-534-101."

Clinical • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Oncternal Therapeutics Announces FDA Granted Fast Track Designation for ONCT-534 for the Treatment of Metastatic Castration-Resistant Prostate Cancer (GlobeNewswire) - "Oncternal Therapeutics, Inc...today announced that the U.S. Food and Drug Administration (FDA) has designated ONCT-534, its novel dual-acting androgen receptor inhibitor (DAARI), as a Fast Track development program for the investigation of the treatment of patients with relapsed or refractory metastatic castration-resistant prostate cancer (mCRPC) resistant to approved androgen receptor pathway inhibitors (ARPIs)."

Fast track designation • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Oncternal Therapeutics Announces First Patient Dosed in Phase 1/2 Study of Dual-Action AR Inhibitor, ONCT-534, in Patients with Metastatic Castration-Resistant Prostate Cancer (GlobeNewswire) - "Oncternal Therapeutics, Inc...today announced that the first patient has been dosed in the Phase 1/2 dose escalation/dose expansion study of ONCT-534, the company’s dual-action androgen receptor inhibitor....We intend to advance the dose escalation portion of the Phase 1/2 Study ONCT-534-101 quickly, and we will be enrolling patients in sites across the U.S. over the coming weeks, and in the United Kingdom in early 2024. We expect to report initial clinical data in the first half of 2024.'"

P1/2 data • Trial status • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

A Clinical Study of ONCT-534 in Subjects With Metastatic Castration-resistant Prostate Cancer. (clinicaltrials.gov) - P1/2 | N=59 | Recruiting | Sponsor: Oncternal Therapeutics, Inc | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Oncternal Therapeutics Announces its Prostate Cancer Scientific Advisory Board (GlobeNewswire) - "Oncternal Therapeutics, Inc...today announced the establishment of its Prostate Cancer Scientific Advisory Board (SAB). The Prostate Cancer SAB is comprised of distinguished academic and industry leaders in the prostate cancer field, which will advise Oncternal as it develops its novel dual-acting androgen receptor inhibitor (DAARI), ONCT-534."

Clinical • Acute Myelogenous Leukemia • Genito-urinary Cancer • Hematological Malignancies • Leukemia • Oncology • Prostate Cancer • Solid Tumor

Oncternal Therapeutics Provides Business Update and Announces Second Quarter 2023 Financial Results (Oncternal Therapeutics Press Release) - "Oncternal Therapeutics, Inc...today provided a business update and reported second quarter 2023 financial results...Expected Upcoming Milestones: ONCT-808...Initial clinical data available by the end of 2023; Additional clinical readouts in 2024...ONCT-534...Initial clinical data available in the first half of 2024."

P1/2 data • Genito-urinary Cancer • Hematological Malignancies • Oncology • Prostate Cancer • Solid Tumor

Oncternal Therapeutics Receives FDA Study May Proceed Letter for ONCT-534, its Novel Dual-action Androgen Receptor Inhibitor, for the Treatment of Patients with Advanced Prostate Cancer (GlobeNewswire) - "Oncternal Therapeutics...announced the receipt of a Study May Proceed letter from the U.S. Food and Drug Administration (FDA), for a Phase 1/2 dose escalation study of ONCT-534, a novel dual-action androgen receptor inhibitor (DAARI), in patients with metastatic castration-resistant prostate cancer (mCRPC) who have relapsed or are refractory to approved androgen receptor signaling inhibitors (ARSIs). The letter was received prior to the 30-day review date."

IND • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

A Clinical Study of ONCT-534 in Subjects With Metastatic Castration-resistant Prostate Cancer. (clinicaltrials.gov) - P1/2 | N=59 | Not yet recruiting | Sponsor: Oncternal Therapeutics, Inc

Metastases • New P1/2 trial • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Oncternal Therapeutics Provides Business Update and Announces First Quarter 2023 Financial Results (GlobeNewswire) - "Expected Upcoming Milestones: ONCT-808, our autologous ROR1-targeted CAR T cell therapy. Initial clinical data available by the end of 2023. Additional clinical readouts in 2024; ONCT-534, our dual-action androgen receptor inhibitor. U.S. IND application submission in mid-2023. Phase 1/2 clinical study initiation in the second half of 2023. Initial clinical data available in the first half of 2024."

IND • New P1/2 trial • P1/2 data • Oncology

Oncternal Therapeutics Announces Strategic Reprioritization, Stops Two Zilovertamab Studies (Yahoo Finance) - "ONCT-534: Dual-action androgen receptor inhibitor (DAARI) has concluded IND-enabling studies and an Investigational New Drug Application (IND) is expected to be submitted in mid-2023. Initial clinical data is expected to be presented in mid-2024."

Clinical data • IND • Oncology