On January 8, 2024 Oncternal Therapeutics, Inc. (Nasdaq: ONCT), a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies, reported 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) (Press release, Oncternal Therapeutics, JAN 8, 2024, View Source [SID1234639098]). 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).

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"The ONCT-534-101 investigators are enthusiastic about this study, and we are excited about the enrollment and progress through the initial dosing levels. Reaching the third cohort represents an important milestone for the program, as we believe we are nearing potentially therapeutic doses that may benefit prostate cancer patients who have progressed after treatment with approved ARPI such as enzalutamide, abiraterone, apalutamide and darolutamide," said Salim Yazji M.D., Chief Medical Officer at Oncternal Therapeutics. "We believe ONCT-534, with its novel mechanism of action involving both the ligand-binding domain and the N-terminal domain of the androgen receptor (AR), may address a significant unmet medical need for patients with advanced metastatic prostate cancer, especially those with splice variants of the AR, mutations in the ligand-binding domain of the AR, or AR amplification, common mechanisms of resistance that may develop to treatment with currently approved AR pathway inhibitors."

About Study ONCT-534-101
Study ONCT-534-101 is a Phase 1/2, single-arm, open-label, multi-center study to evaluate the safety and tolerability, pharmacokinetics, and preliminary anti-tumor activity of ONCT-534 in patients with mCRPC who have relapsed or are refractory to approved ARPIs including enzalutamide, abiraterone, apalutamide and darolutamide. After the safety and tolerability and preliminary antitumor activity of ONCT-534 have been assessed in the Phase 1 portion of this study, Phase 2 will commence to further evaluate the safety and preliminary antitumor activity of ONCT-534 to support selecting an optimal dose.

On January 8, 2024 Olema oncology presented its corporate presentation (Presentation, Olema Oncology, JAN 8, 2024, View Source [SID1234639097]).

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On January 8, 2024 Nurix presented its corporate presentation (Presentation, Nurix Therapeutics, JAN 8, 2024, View Source [SID1234639096]).

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On January 8, 2024 Novartis reported positive results from the primary analysis of ASC4FIRST, a pivotal Phase III trial comparing Scemblix (asciminib) with investigators’ choice of tyrosine kinase inhibitor (TKI) treatment in newly diagnosed patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP)1. ASC4FIRST is the first and only randomized head-to-head Phase III trial comparing a CML treatment vs. approved standard-of-care first- and second-generation TKIs1 (Press release, Novartis, JAN 8, 2024, View Source [SID1234639095]).

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The trial met both primary endpoints of major molecular response (MMR) rate for Scemblix compared to investigator-selected TKIs (imatinib, nilotinib, dasatinib, and bosutinib) and compared to imatinib, demonstrating clinically meaningful and statistically significant results for both endpoints1. Scemblix showed a favorable safety and tolerability profile with fewer adverse events (AEs) and treatment discontinuations vs. investigator selected standard-of-care TKIs1. The ASC4FIRST data showed no new safety signals compared to the established safety profile of Scemblix1,14.

"We are very encouraged by these results given that a significant proportion of patients with newly diagnosed chronic myeloid leukemia, or CML, do not achieve their treatment goals," said Prof. Tim Hughes, MD, South Australian Health & Medical Research Institute (SAHMRI). "There remains a significant need in first-line therapy of CML for tolerable treatment options, allowing people with CML to balance their treatment alongside their quality of life."

Improvements in treatment have transformed CML into a chronic disease, with a life expectancy similar to that of the general population, making tolerability an important treatment goal9. While many patients with CML may benefit from available TKI therapy, intolerance and AEs remain a primary reason for TKI therapy discontinuation, with discontinuation rates due to AEs of up to 25% by five years2-6. Additionally, over 60% of newly diagnosed CML patients fail to meet 12-month molecular response goals 5-13.

"We are excited that Scemblix may help people newly diagnosed with CML achieve their treatment goals while continuing to live their lives," said Shreeram Aradhye, M.D., President, Development and Chief Medical Officer, Novartis. "Given the chronic nature of their condition, patients often need to be on TKI therapy for many years, so treatment options that are well tolerated and highly efficacious are crucial to support adherence. This study outcome builds on our 20-year legacy in CML innovation as we strive to continue to address the remaining unmet needs for people living with this blood cancer."

The trial remains ongoing, with the next scheduled data readout planned for week 96, which will evaluate the key secondary endpoint (MMR at week 96) as well as additional secondary endpoints.

Details will be presented at an upcoming medical conference and included as part of regulatory submissions in 2024.

About ASC4FIRST Phase III Clinical Trial
ASC4FIRST (NCT04971226) is a Phase III, head-to-head, multi-center, open-label, randomized study of oral Scemblix 80 mg QD versus investigator-selected first- or second-generation TKI (imatinib, nilotinib, dasatinib, or bosutinib) in 405 adult patients with newly diagnosed Ph+ CML-CP1. The two primary endpoints of the study are to compare efficacy of asciminib vs. investigator-selected TKI and to compare efficacy vs that of TKI within the stratum of participants with imatinib as pre-randomization selected TKI, based on proportion of patients that achieve MMR at week 481. The study remains ongoing with a key secondary endpoint of proportion of patients that achieve MMR at week 96 and a safety endpoint of discontinuation of study treatment due to an AE (TTDAE) by week 96. The study also assesses additional secondary safety and efficacy endpoints, including MMR, MR4, MR4.5, complete hematological response (CHR) and BCR::ABL1 ≤1% at and by all scheduled data collection time points; duration of and time to first MMR, MR4 and MR4.5; time to treatment failure; event-free survival, failure-free survival, progression-free survival, and overall survival1.

About Scemblix (asciminib)
Scemblix is the first CML treatment that works by specifically targeting the ABL myristoyl pocket15,16 and was intentionally designed to be highly specific and minimize off-target kinase mediated effects, which translates into an improved safety and tolerability profile compared to current standard of care.

Scemblix is approved in more than 60 countries, including the US and the EU, to treat adults with Ph+ CML-CP who have previously been treated with two or more TKIs14,19. In some countries including the US, Scemblix is also approved in patients with Ph+ CML-CP with the T315I mutation2-14,18,19.

Scemblix represents an important potential treatment option for patients who experience resistance and/or intolerance to currently available TKI therapies, and it is being studied across multiple treatment lines for Ph+ CML-CP, both as monotherapy and in combination.

On January 8, 2024 Novartis presented its corporate presentation (Press release, Novartis, JAN 8, 2024, View Source [SID1234639094]).

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