Hi @RaceOncology,

Just what to bring this to your attention.

Kura Oncology doses first subject in Phase I/II HNSCC drug trial

17 Dec 2021 (Last Updated December 17th, 2021 14:11)

Kura and Novartis entered a clinical partnership in July this year to assess tipifarnib plus alpelisib for HNSCC.

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Kura Oncology has dosed the first subject in the Phase I/II KURRENT clinical trial of its oral experimental drug candidate, tipifarnib, plus alpelisib in HRAS-dependent and/or PIK3CA-dependent head and neck squamous cell carcinoma (HNSCC) patients.

Tipifarnib is an orally bioavailable farnesyl transferase inhibitor while Novartis’ alpelisib is an inhibitor of phosphatidylinositol-3-kinase (PI3K).

A biomarker-defined cohort, open-label trial, KURRENT will analyse the safety, identify the combination dose and evaluate initial anti-tumour activity of tipifarnib, along with alpelisib to treat subjects with HRAS- and/or PIK3CA-dependent HNSCC.

The preliminary arm of the trial enrolled subjects with PIK3CA-dependent HNSCC.

Kura and Novartis signed a clinical partnership in July 2021 to assess tipifarnib plus alpelisib in HNSCC patients.

According to the deal, Kura holds worldwide development and marketing rights to tipifarnib.

Kura Oncology president and CEO Troy Wilson said: “Despite the approval of immunotherapy, the treatment of recurrent and metastatic HNSCC remains a significant unmet need.

“The KURRENT trial builds on the impressive clinical activity reported for tipifarnib as a monotherapy in HRAS mutant HNSCC and represents an opportunity to significantly expand the potential patient population and target mechanisms of drug resistance.”

According to preclinical data, HRAS and PI3kα are mutually-dependent oncogenes in HNSCC and the combination of tipifarnib and a PI3Kα inhibitor could potentially offer improved antitumor activity as against hindering each target alone.

Last month, the US Food and Drug Administration placed a partial clinical hold on Kura Oncology’s Phase Ib KOMET-001 trial of KO-539 to treat in relapsed or refractory acute myeloid leukaemia.

The move comes after a Grade 5 serious adverse event of patient death probably linked to differentiation syndrome was reported in the trial.

https://www.clinicaltrialsarena.com/news/kura-oncology-doses-hnscc-trial/

FDA puts clinical hold on Kura Oncology’s Phase Ib AML therapy trial

24 Nov 2021 (Last Updated November 24th, 2021 14:47)

The FDA’s decision is based on a report in which a Grade 5 serious adverse event of death was reported in the trial.

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The US Food and Drug Administration (FDA) has placed a partial clinical hold on Kura Oncology’s Phase Ib KOMET-001 clinical trial of its drug candidate, KO-539, in relapsed or refractory acute myeloid leukaemia (AML) patients.

KO-539 is a potent and selective inhibitor of menin.

The FDA’s partial clinical hold comes in response to the latest report submitted by the company of a Grade 5 serious adverse event of patient death probably connected to differentiation syndrome.

This syndrome is a recognised side effect linked to differentiating agents in the AML treatment.

Kura noted that the subjects currently enrolled in the trial could continue to take KO-539 but no new subjects will be enrolled until the FDA lifts the partial clinical hold.

The company is holding talks with FDA as well as trial investigators to address the clinical hold soon.

Kura Oncology president and CEO Troy Wilson said: “Differentiation syndrome is known to be an on-target effect associated with therapeutic agents that induce differentiation, and we want to ensure physicians are fully informed and prepared to address these events if they occur.

“Based on the totality of preclinical and clinical data, we continue to believe that KO-539 has the potential to address the significant unmet medical need of AML patients, including those with NPM1 mutations and KMT2A rearrangements.”

The company will temporarily delay the guidance on the conclusion on patient enrolment in the trial and selection of the recommended dose of the drug for the Phase II trial.

In addition to KO-539, Kura has several small molecule therapy candidates in its pipeline. Its tipifarnib, an orally bioavailable inhibitor of farnesyl transferase, is currently being analysed in a trial in individuals with HRAS-mutant head and neck squamous cell cancer.

Another farnesyl transferase inhibitor, KO-2806, is being developed for oncology indications.

In August this year, the FDA placed a clinical hold on Aprea Therapeutics’ trial of eprenetapopt to treat lymphoid malignancies.

https://www.clinicaltrialsarena.com/news/fda-clinical-hold-kura-aml/

Not sure if this is related to us, but I thought it didn't hurt, has it mentioned R/R Acute Myeloid Leukaemia (AML) trial.

IMHO.

Regard's

Rossi70