Kura Oncology Doses First Patient in KOMET-008 Trial of Ziftomenib in Combination with Standards of Care, Including FLT3 Inhibitor, in Acute Myeloid Leukemia

Rhea-AI Summary

Kura Oncology initiates Phase 1 trial KOMET-008 to evaluate ziftomenib in combination with gilteritinib, FLAG-IDA, or LDAC for NPM1-mutant or KMT2A-rearranged AML patients, aiming to provide a new treatment option with promising safety and efficacy profiles.

Insights

Oncology Doctor

The initiation of the KOMET-008 Phase 1 trial by Kura Oncology represents a significant step in the development of combination therapies for acute myeloid leukemia (AML), particularly for patients with NPM1 mutations or KMT2A rearrangements. These genetic alterations are known to be associated with a poor prognosis, especially when compounded by FLT3 mutations. The combination of ziftomenib, a menin inhibitor, with gilteritinib, an FLT3 inhibitor, has the potential to target these mutations more effectively. The rationale for such a combination is rooted in the synergistic effects observed in preclinical studies, suggesting that the dual targeting of menin and FLT3 pathways could lead to improved outcomes in this patient subset.

From a clinical perspective, the safety and tolerability profile of this combination therapy is paramount, as AML treatments can often be associated with significant toxicity. The reported potential best-in-class safety profile of ziftomenib, if substantiated in this trial, could represent a therapeutic advantage. Additionally, the pharmacokinetic data will be crucial in understanding how these drugs interact and the optimal dosing regimen to maximize efficacy while minimizing adverse effects.

Medical Research Analyst

As the first trial to evaluate the combination of a menin inhibitor with an FLT3 inhibitor in AML, KOMET-008 could have substantial implications for the treatment landscape of AML. The trial's design, which includes dose escalation cohorts, is critical for establishing the maximum tolerated dose and preliminary efficacy. The inclusion of pharmacokinetic studies will inform on how ziftomenib is processed in the body when used in combination with other drugs, which is essential for understanding potential drug-drug interactions and their impact on patient safety.

For stakeholders, the progress of this trial is a key indicator of Kura Oncology's pipeline strength and its commitment to precision medicine. Positive outcomes from this trial could lead to an increase in the company's valuation due to the potential market expansion for ziftomenib. However, it is important to note that the trial is in its early stages and the efficacy and safety profiles of the combination therapy are yet to be established. The investment community will be watching closely for any interim analyses or preliminary results that could provide early indications of the combination's potential.

Market Research Analyst

The strategic focus on precision medicine and the development of targeted therapies in oncology is a growing trend and Kura Oncology's efforts with ziftomenib align with this direction. The market for AML treatments is competitive, but the specificity of ziftomenib for NPM1-mutant or KMT2A-rearranged AML could carve out a niche market segment for the drug if successful. It is also noteworthy that there are no other actively recruiting clinical trials evaluating the combination of a menin inhibitor with a FLT3 inhibitor, which could give Kura a competitive advantage if their trial results are positive.

Long-term benefits for the company hinge on the trial's outcomes, which could lead to breakthrough therapy designation and expedited development pathways if the data is compelling. The market's response to these developments will likely be positive, but it is crucial to remain aware of the inherent risks and uncertainties in drug development. Investors and analysts will be evaluating Kura's strategic partnerships, potential for commercialization and overall portfolio diversification when considering the company's future prospects.

– KOMET-008 is evaluating ziftomenib in combination with gilteritinib, FLAG-IDA or LDAC in patients with relapsed/refractory NPM1-mutant or KMT2A-rearranged AML –

SAN DIEGO, Feb. 26, 2024 (GLOBE NEWSWIRE) -- Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, today announced that the first patient has been dosed in KOMET-008, the Company’s Phase 1 trial of its menin inhibitor ziftomenib, in combination with gilteritinib, FLAG-IDA or LDAC for the treatment of NPM1-mutant or KMT2A-rearranged acute myeloid leukemia (AML).

“Roughly half of patients with relapsed or refractory NPM1-mutant AML have co-occurring FLT3 mutations, and the prognosis for these patients is particularly poor,” said Stephen Dale, M.D., Chief Medical Officer of Kura Oncology. “Given the potential best-in-class safety and tolerability profile as well as the robust monotherapy activity observed in our Phase 1 study of ziftomenib, we believe an all-oral combination of ziftomenib and gilteritinib may provide an attractive treatment option for these patients.”

KOMET-008 is a Phase 1 study designed to assess safety and tolerability, pharmacokinetics and evidence of clinical activity of ziftomenib in combination with gilteritinib, FLAG-IDA or LDAC for two genetically defined cohorts, NPM1-mutant AML and KMT2A-rearranged AML, in the relapsed/refractory setting. Trial participants will be enrolled in one of five dose escalation cohorts, including a cohort of NPM1-mutant AML patients with a documented FLT3 co-mutation, who will be treated in combination with the FLT3 inhibitor gilteritinib. For more information regarding KOMET-008, please visit www.clinicaltrials.gov (identifier: NCT06001788).

Kura is conducting a series of studies to evaluate ziftomenib in combination with current standards of care in earlier lines of therapy and across multiple patient populations. In July, the Company began dosing patients in the first of these studies, KOMET-007, in combination with venetoclax and azacitidine in patients with relapsed/refractory NPM1-mutant and KMT2A-rearranged AML or in combination with standard induction cytarabine/daunorubicin chemotherapy (7+3) in patients with previously untreated NPM1-mutant and KMT2A-rearranged AML. Kura reported positive preliminary data from 20 patients in KOMET-007 on January 30, 2024.

Preclinical data for menin inhibitors in combination with multiple FLT3 inhibitors demonstrate strong synergistic effects compared to either single agent alone. Currently there are no other actively recruiting clinical trials evaluating the combination of a menin inhibitor with a FLT3 inhibitor for the treatment of AML.

About Acute Myeloid Leukemia

AML is the most common acute leukemia in adults and begins when the bone marrow makes abnormal myeloblasts (white blood cells), red blood cells or platelets. Despite the many available treatments for AML, prognosis for patients remains poor and a high unmet need remains. The menin pathway is considered a driver for multiple genetic alterations of the disease, of which NPM1 mutations are among the most common, representing approximately 30% of AML cases and KMT2A rearrangements represent approximately 5-10% of AML cases. While patients with NPM1-m AML have high response rates to frontline therapy, relapse rates are high and survival outcomes are poor, with only 30% overall survival at 12 months in the R/R setting. Additionally, NPM1 mutations frequently occur with co-mutations in other disease-associated genes, including FLT3, DNMT3A and IDH1/2, with prognosis heavily influenced by the presence of co-occurring mutations. Adult patients with NPM1-m AML and select co-mutations and/or R/R disease have a poor prognosis, with median overall survival of only approximately 7.8 months in 2nd line, 5.3 months in 3rd line and 3.5 months following the 4th line¹. Adult patients with KMT2A-r AML have a poor prognosis with high rates of resistance and relapse following standard of care, with median overall survival for this patient population of only 6 months following 2nd line and 2.4 months following 3rd line². No FDA-approved therapies targeting NPM1-m and KMT2A-r AML currently exist.

About Ziftomenib

Ziftomenib is a novel, once-daily, oral investigational drug candidate targeting the menin-KMT2A/MLL protein-protein interaction for treatment of genetically defined AML patients with high unmet need. Ziftomenib inhibits the KMT2A/MLL protein complex and exhibits downstream effects on HOXA9/MEIS1 expression and potent anti-leukemic activity in genetically defined preclinical models of AML. Ziftomenib has received Orphan Drug Designation from the U.S. Food and Drug Administration for the treatment of AML. Additional information about clinical trials for ziftomenib can be found at kuraoncology.com/clinical-trials/#ziftomenib.

About Kura Oncology

Kura Oncology is a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer. The Company’s pipeline consists of small molecule drug candidates that target cancer signaling pathways. Ziftomenib is a once-daily, oral drug candidate targeting the menin-KMT2A protein-protein interaction for the treatment of genetically defined AML patients with high unmet need. Kura is currently enrolling patients in a Phase 2 registration-directed trial of ziftomenib in NPM1-mutant relapsed or refractory AML (KOMET-001). The Company is also conducting a series of studies to evaluate ziftomenib in combination with current standards of care, beginning with venetoclax and azacitidine and 7+3 in NPM1-mutant and KMT2A-rearranged newly diagnosed and relapsed/refractory AML (KOMET-007). Tipifarnib, a potent and selective farnesyl transferase inhibitor (FTI), is currently in a Phase 1/2 trial in combination with alpelisib for patients with PIK3CA-dependent head and neck squamous cell carcinoma (KURRENT-HN). Kura is also evaluating KO-2806, a next-generation FTI, in a Phase 1 dose-escalation trial as a monotherapy and in combination with adagrasib in KRAS^G12C-mutated non-small cell lung cancer and cabozantinib in clear cell renal cell carcinoma (FIT-001). For additional information, please visit Kura’s website at www.kuraoncology.com and follow us on X and LinkedIn.

Forward-Looking Statements

This news release contains certain forward-looking statements that involve risks and uncertainties that could cause actual results to be materially different from historical results or from any future results expressed or implied by such forward-looking statements. Such forward-looking statements include statements regarding, among other things, the efficacy, safety and therapeutic potential of ziftomenib, potential benefits of combining ziftomenib with appropriate standards of care, and progress and expected timing of the ziftomenib program and clinical trials. Factors that may cause actual results to differ materially include the risk that compounds that appeared promising in early research or clinical trials do not demonstrate safety and/or efficacy in later preclinical studies or clinical trials, the risk that Kura may not obtain approval to market its product candidates, uncertainties associated with performing clinical trials, regulatory filings, applications and other interactions with regulatory bodies, risks associated with reliance on third parties to successfully conduct clinical trials, risks associated with reliance on outside financing to meet capital requirements, and other risks associated with the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs. You are urged to consider statements that include the words “may,” “will,” “would,” “could,” “should,” “believes,” “estimates,” “projects,” “promise,” “potential,” “expects,” “plans,” “anticipates,” “intends,” “continues,” “designed,” “goal,” or the negative of those words or other comparable words to be uncertain and forward-looking. For a further list and description of the risks and uncertainties the Company faces, please refer to the Company's periodic and other filings with the Securities and Exchange Commission, which are available at www.sec.gov. Such forward-looking statements are current only as of the date they are made, and Kura assumes no obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.

Contacts

Investors:
Pete De Spain
Executive Vice President, Investor Relations &
Corporate Communications
(858) 500-8833
pete@kuraoncology.com

Media:
Alexandra Weingarten
Associate Director, Corporate Communications &
Investor Relations
(858) 500-8822
alexandra@kuraoncology.com

¹ Issa GC, et al. Blood Adv. 2023;7(6):933-42.
² Issa GC, et al. Blood Cancer J. 2021;11(9):162.

FAQ

What is the purpose of KOMET-008 trial by Kura Oncology?

KOMET-008 is a Phase 1 trial evaluating ziftomenib in combination with gilteritinib, FLAG-IDA, or LDAC for NPM1-mutant or KMT2A-rearranged AML patients.

What are the key objectives of KOMET-008 trial?

The trial aims to assess safety, tolerability, pharmacokinetics, and clinical activity of ziftomenib in combination with specified drugs for genetically defined AML cohorts.

Which patient populations are targeted in KOMET-008 trial?

The trial focuses on patients with relapsed/refractory NPM1-mutant or KMT2A-rearranged AML, particularly those with FLT3 co-mutations.

What are the unique aspects of the combination therapy in KOMET-008 trial?

KOMET-008 is unique as it combines a menin inhibitor, ziftomenib, with gilteritinib, FLAG-IDA, or LDAC, offering a potentially effective all-oral treatment option.

What is the significance of the preliminary data from KOMET-007 study?

Positive preliminary data from KOMET-007 indicate the potential efficacy of ziftomenib in combination with other drugs for AML treatment.