CLINICAL TRIAL PROGRAMS

Kura Oncology’s clinical trial programs represent the next step toward our goal of realizing the full potential of precision medicine. Our investigational trials are studying innovative therapeutic candidates with the potential to help patients with certain cancers live better, longer lives.

INVESTIGATIONAL THERAPIES

Ziftomenib
A Menin Inhibitor

Tipifarnib
A Farnesyl Transferase Inhibitor

DISCOVER CLINICAL TRIAL PROGRAMS FOR:

ACUTE LEUKEMIAS

Acute myeloid leukemia (AML)

HNSCC

Head and neck squamous cell carcinoma

NSCLC

Non-small cell lung cancer

MENIN INHIBITOR TRIALS: ZIFTOMENIB

Clinical trials studying ziftomenib in patients with acute leukemias

ACUTE LEUKEMIAS

AML is a genetically heterogenous disease.1 Two alterations observed in AML are KMT2A rearrangements (KMT2A-r) and NPM1 mutations (NPM1-m); about 5-10% of patients have translocations of the KMT2A gene, whereas 25-30% of patients have NPM1-m with or without other gene mutations.2,3

While patients with NPM1-m have high response rates to first-line therapy, survival outcomes remain poor, with a five-year survival rate of ~50%. Patients with NPM1-m with co-mutations or who are relapsed/refractory (R/R) also have a poor prognosis. Patients with KMT2A-r have high rates of resistance to current treatments and relapse, with a five-year overall survival of less than 20%.4-7

  • 5-YEAR SURVIVAL RATE4-7

NPM1-m: ~50%

KMT2A-r: <20%

  • RECRUITING

Relapsed/refractory AML Phase 1/2

KOMET-001 is a phase 1/2 study of ziftomenib in patients with NPM1-m or KMT2A-r R/R AML.

The goal of phase 1 is to determine the safety, tolerability, pharmacokinetics and recommended phase 2 dose (RP2D) of ziftomenib.

KMT2A-R AML

of patients with AML have translocations of the KMT2A gene.2

NPM1-M AML

of patients with AML have NPM1-m with or without other gene mutations.3

FARNESYL TRANSFERASE INHIBITOR TRIALS: TIPIFARNIB

Clinical trials studying tipifarnib in patients with HNSCC or NSCLC

HEAD AND NECK SQUAMOUS CELL CARCINOMA (HNSCC)

The five-year overall survival for patients with stage III or IV head and neck cancer is around 15-35%.10 Despite recent advances in treatment, including the incorporation of immunotherapy, prognosis remains poor — especially in patients with recurrent/metastatic (R/M) disease — with the median survival ranging from six to 15 months depending on patient- and disease-related factors.11-13

  • 5-YEAR SURVIVAL RATE10

Stage III/IV HNSCC: ~15 – 35%

COMPLETED

RELAPSED/REFRACTORY HNSCC PHASE 2

RUN-HN is a completed phase 2 study of the antitumor activity and overall response rate of tipifarnib in patients with HRAS-m HNSCC.

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RELAPSED/REFRACTORY HNSCC PHASE 2

AIM-HN is a registration-directed study designed to evaluate the efficacy and tolerability of tipifarnib in patients with HRAS-m HNSCC.

  • RECRUITING

RELAPSED/REFRACTORY HNSCC PHASE 1/2

KURRENT-HN is a phase 1/2 open-label, dose escalation study of tipifarnib and alpelisib, a PI3K alpha inhibitor, to determine the safety and recommended dose and regimen for the treatment of adult patients with R/M HNSCC whose tumors are HRAS-dependent and PIK3CA-dependent. The codependency of HRAS and PI3K pathways in driving tumor growth provides the rationale for a combination trial of tipifarnib and alpelisib in this subset of patients with HNSCC.

HRAS MUTATIONS AND/OR OVEREXPRESSION OCCUR IN

of patients with HNSCC.14

PIK3CA MUTATIONS OR AMPLIFICATIONS ARE FOUND IN

of patients with HNSCC.15

NON-SMALL CELL LUNG CANCER (NSCLC)

Lung cancer is the world’s second most commonly diagnosed cancer; NSCLC is the most prevalent type of lung cancer in the United States, making up 82% of all lung cancer diagnoses.

The 5-year survival rate for NSCLC is 26%.9

Many patients with NSCLC treated with EGFR-targeted drugs will develop acquired resistance.16

  • 5-YEAR SURVIVAL RATE9

NSCLC: ~26%

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FRONT-LINE NSCLC PHASE 1

KURRENT-LUNG is a phase 1 study of tipifarnib in combination with osimertinib in patients with treatment-naïve advanced or metastatic EGFR-m NSCLC. The KURRENT-LUNG study is expected to open in Q3 of 2022.

Please contact Kura Oncology to learn more about trial details for KURRENT-LUNG.

EGFR MUTATIONS OCCUR IN

of patients with NSCLC.17

REFERENCES

  • 1. Kumar CC. Genetic abnormalities and challenges in the treatment of acute myeloid leukemia. Genes Cancer. 2011;2(2):95-107. 2. Klossowski S, Miao H, Kempinska K, et al. Menin inhibitor MI-3454 induces remission in MLL1-rearranged and NPM1-mutated models of leukemia. J Clin Invest. 2020;130(2):981-997. 3. Prata PH, Bally C, Prebet T, et al. NPM1 mutation is not associated with prolonged complete remission in acute myeloid leukemia patients treated with hypomethylating agents. Haematologica. 2018;103(10):e455-e457. 4. Angenendt L, Röllig C, Montesinos P, et al. Chromosomal abnormalities and prognosis in NPM1-mutated acute myeloid leukemia: a pooled analysis of individual patient data from nine international cohorts. J Clin Oncol. 2019;37(29):2632-2642. 5. Venugopal S, Konopleva M, DiNardo CD, et al. NPM1 mutations do not retain a favorable prognostic impact in adults with advanced relapsed or refractory (R/R) acute myeloid leukemia (AML). Poster presented at: 2021 ASH Meeting on Hematologic Malignancies; September 2-3, 2021; virtual. Abstract 2287. 6. Döhner H, Estey E, Grimwade D, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129(4):424-447. 7. Issa GC, Zarka J, Sasaki K, et al. Predictors of outcomes in adults with acute myeloid leukemia and KMT2A rearrangements. Blood Cancer J. 2021;11(9):162. 8. Terwilliger T, Abdul-Hay M. Acute lymphoblastic leukemia: a comprehensive review and 2017 update. Blood Cancer J. 2017;7(6):e577. 9. American Cancer Society. Cancer Facts & Figures 2022. Atlanta: American Cancer Society; 2022. 10. Ridge JA, Glisson BS, Lango MN. Head and neck tumors. February 18, 2011. Accessed July 13, 2022. https://www.cancernetwork.com/view/head-and-neck-tumors 11. Brockstein BE, Vokes EE. Treatment of metastatic and recurrent head and neck cancer. UpToDate. 2020. Accessed October 8, 2021. https://www.uptodate.com/contents/treatment-of-metastatic-and-recurrent-head-and-neck-cancer/print 12. Bauml J, Seiwert TY, Pfister DG, et al. Pembrolizumab for platinum- and cetuximab-refractory head and neck cancer: results from a single-arm, phase II study. J Clin Oncol. 2017;35(14):1542-1549. 13. Ferris RL, Blumenschein G Jr, Fayette J, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med. 2016;375(19):1856-1867. 14. Burrows F, Shivani M, Wang Z, Chan S, Gilardi M, Gutkind S. Antitumor activity of tipifarnib and PI3K pathway inhibitors in HRAS-associated head and neck squamous cell carcinoma. Europ J Cancer. 2020;138:S43-S44. 15. Dilmaghani NA, Safaroghli-Azar A, Pourbagheri-Sigaroodi A, Bashash D. The PI3K/Akt/mTORC signaling axis in head and neck squamous cell carcinoma: possibilities for therapeutic interventions either as single agents or in combination with conventional therapies. IUBMB Life. 2021;73(4):618-642. 16. Tulpule A, Bivona TG. Acquired resistance in lung cancer. Annu Rev Cancer Biol. 2020;4:279-297. 17. Rosell R, Moran T, Queralt C. Screening for epidermal growth factor receptor mutations in lung cancer. N Engl J Med. 2009;361(10):958-967.