darlifarnib (KO-2806) / Kura Oncology - LARVOL DELTA

Forecasted Milestones (GlobeNewswire) - "Initiate FIT-001 Phase 1b expansion cohorts of darlifarnib and cabozantinib in patients with advanced RCC in the first half of 2026. Present updated dose-escalation data from the combination of darlifarnib and cabozantinib in patients with advanced RCC in 2026. Present preliminary clinical data from the combination of darlifarnib and adagrasib in patients with KRASG12C-mutated solid tumor indications in 2026."

P1 data • Trial status • Colorectal Cancer • Non Small Cell Lung Cancer • Pancreatic Ductal Adenocarcinoma • Renal Cell Carcinoma

The farnesyl transferase inhibitor KO-2806 constrains mTORC1 activity to enhance the antitumor efficacy of mutant-selective PI3Kα inhibitors (AACR-NCI-EORTC 2025) - "We have previously demonstrated farnesyl transferase inhibitors (FTIs) enhance the antitumor activity of multiple targeted therapies, including the α-selective PI3K inhibitor alpelisib, by blocking RHEB-mediated mTORC1 activation...In this study, we assessed the potential therapeutic utility of combining KO-2806 with mutant-selective PI3Kα inhibitors STX-478 or RLY-2608 in a panel of in vitro cell line and in vivo xenograft models spanning the breadth of solid tumor indications with the highest frequency of PIK3CA mutation...In the ER+ model MCF7, combination of KO-2806 and RLY-2608 was comparable to combination of fulvestrant and RLY-2608, resulting in tumor regressions, while the triplet further deepened tumor regression. These data suggest that, due to its ability to constrain mTORC1 signaling, KO-2806 holds promise as a combination agent for mutant-selective PI3Kα inhibitors across a broad range of PIK3CA-mutant solid tumor indications."

Clinical • Bladder Cancer • Colorectal Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • AKT1S1 • PIK3CA • RHEB

Farnesyltransferase inhibitor (FTI) KO-2806 in combination with cabozantinib (cabo) in renal cell carcinoma (RCC): Preliminary results from FIT-001 phase I trial (ESMO 2025) - P1 | "Updated data to be presented. Conclusions KO-2806 + cabo combo demonstrates clinical activity in cabo-naïve and -resistant RCC with a manageable safety profile, supporting further investigation of KO-2806 combos in RCC and other advanced cancers."

Combination therapy • P1 data • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

A phase I study of the next-generation farnesyltransferase inhibitor (FTI) KO-2806 as monotherapy in advanced solid tumors (ESMO 2025) - P1 | "The FTI tipifarnib demonstrated promising clinical activity among m HRAS tumors, supporting the potential utility of KO-2806 in these settings. Encouraging antitumor activity was observed in advanced m HRAS solid tumors with a broad therapeutic window. These data support further exploration of its combinatorial potential."

Metastases • Monotherapy • P1 data • Colorectal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Thyroid Gland Carcinoma • HRAS • KRAS

Kura Oncology Announces Preliminary Data from Its Farnesyl Transferase Inhibitor (FTI) Programs at the 2025 European Society for Medical Oncology (ESMO) Congress (GlobeNewswire) - "Manageable safety and tolerability profile at doses from 3 to 10 mg per day; Encouraging antitumor activity in advanced HRAS-m solid tumors across multiple dose levels, demonstrating on-target activity and a broad therapeutic window...Antitumor activity observed across all doses in RCC, including in prior cabozantinib-exposed patients; ORR: 33%–50% in ccRCC (17-50% in patients with prior cabozantinib exposure); DCR: 80%–100% in ccRCC....Dose-escalation study ongoing and Phase 1b dose-expansion planned to assess optimal biologically active dose for combination."

P1 data • Clear Cell Renal Cell Carcinoma • Renal Cell Carcinoma

Kura Oncology to Host Virtual Investor and Analyst Events on Farnesyl Transferase Inhibitor Program (GlobeNewswire) - "September 16 event to highlight preclinical data on the combination of FTI agents with multiple classes of targeted therapies; October 18 event to review clinical data from the ESMO Congress 2025, including first clinical data from KO-2806."

Clinical data • Preclinical • Oncology • Solid Tumor

Kura Oncology Highlights Preclinical Data Demonstrating Potential of Farnesyl Transferase Inhibitors to Overcome Drug Resistance in Combination with Key Targeted Therapies Across Multiple Tumor Types (GlobeNewswire) - "In preclinical non-small cell lung cancer (NSCLC) and colorectal cancer (CRC) models, KO-2806 re-sensitizes tumors to both mutant-selective or pan-KRAS inhibitors, restoring responsiveness in these models of relapsed settings."

Preclinical • Colorectal Cancer • Non Small Cell Lung Cancer

Menin Inhibitors in KMT2A-Rearranged and NPM1-Mutated Acute Leukemia: A Scoping Review of Safety and Efficacy (SOHO 2025) - " Thirteen clinical trials evaluating six menin inhibitors—revumenib (SNDX-5613), ziftomenib (KO-539), bleximenib (KO-2806), enzomenib (DS-1594), BMF-219, and JNJ-75276617—were analyzed. These findings demonstrate the potent efficacy of menin inhibitors in genetically defined subsets of leukemia. However, their clinical application requires careful management of toxicity profiles, including QTc prolongation and differentiation syndrome. Additionally, menin inhibitors exhibit synergistic effects with agents like venetoclax and FLT3 inhibitors, enhancing therapeutic efficacy and potentially improving outcomes in KMT2A-rearranged and NPM1-mutated AML."

Clinical • Review • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3 • KMT2A • NPM1

Kura Oncology Reports Second Quarter 2025 Financial Results (Kura Oncology Press Release) - "Forecasted Milestones: Initiate one or more FIT-001 expansion cohorts of KO-2806 and cabozantinib in patients with advanced renal cell carcinoma in the second half of 2025. Present data from the FIT-001 Phase 1 trial evaluating KO-2806 and cabozantinib in patients with renal cell carcinoma at the 2025 ESMO Congress in October 2025. Present data from the FIT-001 Phase 1 monotherapy dose escalation of KO-2806 in patients with RAS-mutant solid tumors at the 2025 ESMO Congress in October 2025. Present data from the KURRENT-HN trial evaluating tipifarnib and alpelisib in PIK3CA-dependent HNSCC at the 2025 ESMO Congress in October 2025."

P1 data • P1/2 data • Trial status • Renal Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

A Phase 1 Clinical Trial of the Farnesyltransferase Inhibitor KO-2806 in Combination with Cabozantinib in Renal Cell Carcinoma (KCRS 2025) - P1, P2 | "Recent clinical trials (NCT03719690, NCT02383927) of the FTI tipifarnib in patients with HRAS-mutant (HRAS-m) head and neck squamous cell carcinoma harboring high variant allele frequency mutations (VAF ≥20%) showed objective response rates of up to 50% and favorable long-term outcomes...The study began accrual in October 2023, and recruitment is ongoing. Significance & Vision FIT-001 is assessing the safety, tolerability, pharmacokinetics, PD, and preliminary antitumor activity of KO-2806 in combination with cabozantinib in patients with ccRCC and non-ccRCC."

Clinical • Combination therapy • IO biomarker • P1 data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Head and Neck Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • HRAS

Farnesyl transferase inhibitor KO-2806 enhances the antitumor activity of cabozantinib in ccRCC tumors that progress on anti-VEGFR agents (AACR 2025) - P1, P3 | "The combination of KO-2806 and cabozantinib led to deeper and more consistent tumor growth inhibition than cabozantinib alone in tumor models that had progressed on axitinib or lenvatinib, two TKIs used to treat RCC...Taken together, our findings demonstrate that KO-2806 augments the antitumor activity of cabozantinib, even after prior exposure to anti-VEGFR treatment, largely by enhancing anti-angiogenesis via mTORC1 signaling inhibition in endothelial cells. These data strongly support our clinical evaluation of KO-2806 as a combination partner with cabozantinib in ccRCC as part of the ongoing Phase 1 FIT-001 trial (NCT06026410)."

Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CD31 • PECAM1 • RHEB

Kura Oncology Reports First Quarter 2025 Financial Results (GlobeNewswire) - "Forecasted Milestones:...(i) Initiate one or more FIT-001 expansion cohorts of KO-2806 and cabozantinib in patients with advanced renal cell carcinoma in the second half of 2025; (ii) Present data from the FIT-001 Phase 1 trial evaluating KO-2806 and cabozantinib in patients with renal cell carcinoma in the second half of 2025; (iii) Present data from the FIT-001 Phase 1 monotherapy dose escalation of KO-2806 in patients with RAS mutations in the second half of 2025; (iv) Present data from the KURRENT-HN trial evaluating tipifarnib and alpelisib in PIK3CA-dependent head and neck squamous cell carcinoma (HNSCC) in the second half of 2025."

Clinical data • Trial status • Renal Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Kura Oncology Announces Preclinical Data for KO-2806 Selected for Oral Presentation at the 2025 AACR Annual Meeting (GlobeNewswire) - "Kura Oncology, Inc...today announced that an abstract containing preclinical data for KO-2806...in combination with cabozantinib...in clear cell renal cell carcinoma (ccRCC), has been accepted for an oral presentation at the upcoming American Association for Cancer Research (AACR) Annual Meeting in Chicago, IL on April 29, 2025....We continue to make good progress in our FIT-001 trial evaluating KO-2806 in solid tumor indications where there is unmet medical need, and we look forward to presenting the first clinical data for KO-2806 as monotherapy and in combination with cabozantinib for the treatment of RCC later this year."

P1 data • Preclinical • Clear Cell Renal Cell Carcinoma

Kura Oncology Reports Fourth Quarter and Full Year 2024 Financial Results (GlobeNewswire) - "Forecasted Milestones: Initiate one or more expansion cohorts of KO-2806 and cabozantinib in patients with advanced renal cell carcinoma in the first half of 2025; Present data from the Phase 1 monotherapy dose escalation of KO-2806 in patients with RAS mutations in the second half of 2025; Present data from the Phase 1 trial evaluating KO-2806 and cabozantinib in patients with renal cell carcinoma in the second half of 2025."

P1 data • Trial status • Genito-urinary Cancer • Renal Cell Carcinoma

2025 Anticipated Clinical Data Highlights (GlobeNewswire) - "(i) FIT-001 Phase 1 data of KO-2806 monotherapy in HRAS-mutant and KRAS-mutated solid tumors (2H 2025); (ii) FIT-001 Phase 1 data of KO-2806 in combination with cabozantinib in renal cell carcinoma (RCC) (2H 2025); (iii) KURRENT-HN Phase 1 data of tipifarnib in combination with alpelisib in PIK3CA-dependent head and neck squamous cell carcinoma (HNSCC) (2H 2025)."

P1 data • Renal Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Kura Oncology Reports Third Quarter 2024 Financial Results (GlobeNewswire) - "Forecasted Milestones: (i) Initiate proof-of-concept study evaluating ziftomenib and imatinib in patients with advanced GIST in the first half of 2025; (ii) Identify the maximum tolerated dose for KO-2806 as a monotherapy in the second half of 2024; (iii) Initiate one or more expansion cohorts for the combination of KO-2806 and cabozantinib in renal cell carcinoma in the first half of 2025."

New trial • Trial status • Gastrointestinal Stromal Tumor • Renal Cell Carcinoma

KO-2806, a next-generation farnesyl transferase inhibitor, re-sensitizes KRAS G12C NSCLC tumors to KRAS G12C mutant-specific inhibitors through mTOR signaling inhibition (EORTC-NCI-AACR 2024) - P1 | "Background: The approval of the KRASG12C mutant-selective inhibitors sotorasib and adagrasib has revolutionized the clinical landscape of non-small cell lung cancer (NSCLC); however, adaptive resistance due to compensatory reactivation of mTOR and MAPK signaling pathways limits their clinical effectiveness...This KO-2806/adagrasib combination is part of FIT-001, a phase 1 first-in-human clinical trial of KO-2806 as a monotherapy and in combination with targeted anti-tumor agents (NCT06026410)... Our findings demonstrate that KO-2806 is effective at overcoming adaptive resistance to KRASG12C inhibitors in KRAS inhibitor-pretreated animals by robust inhibition of adaptive compensatory mTOR activation. Taken together with our previous results, this new data strengthens the therapeutic case for farnesyl transferase inhibition in combination with adagrasib in KRASG12C NSCLC patients irrespective of prior KRAS inhibitor treatment."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EIF4EBP1 • KRAS • RHEB

The next-generation farnesyl transferase inhibitor KO-2806 sensitizes colorectal cancers to pan-RAS inhibition (EORTC-NCI-AACR 2024) - "Indeed, in the KRAS-mutant CDX GP2D, cetuximab only modestly improved tumor growth inhibition by RMC-6236 and was inferior to the RMC-6236/KO-2806 doublet, which led to deep tumor regressions. Farnesyl transferase inhibition controls persistent mTOR signaling mediated by elevated RTK activity in KRAS-mutant CRC. Based on these new data, KO-2806 holds promise as a partner agent to augment the therapeutic potential of pan-RAS inhibitors in this disease."

Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Oncology • Solid Tumor • EIF4EBP1 • KRAS • PIK3CA • RHEB

Kura Oncology to Present New Data Supporting Combination of KO-2806 with KRAS G12C and Pan-RAS Inhibitors (GlobeNewswire) - "Kura Oncology... announced the upcoming presentation of new preclinical data supporting the combination of its next-generation farnesyl transferase inhibitor (FTI) KO-2806 with targeted therapies, including KRASG12C inhibitors and pan-RAS inhibitors, at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics....'We look forward to presenting an update to our growing body of preclinical and clinical data that demonstrate the potential of KO-2806 as a companion therapeutic to augment the antitumor activities of KRASG12C and pan-RAS inhibitors'....'These findings support the promising therapeutic strategy of blunting the effects of innate and adaptive resistance to targeted agents to treat cancers driven by KRAS mutations, including KRASG12C non-small cell lung cancer (NSCLC) and KRAS-mutant colorectal cancers'."

Clinical data • Preclinical • Colorectal Cancer • Non Small Cell Lung Cancer

Kura Oncology Reports Second Quarter 2024 Financial Results (GlobeNewswire) - "Identify the maximum tolerated dose for KO-2806 as a monotherapy in the second half of 2024; Complete enrollment of two expansion cohorts in KURRENT-HN and identify the optimal biologically active dose of tipifarnib and alpelisib by the end of 2024; Present data from the KURRENT-HN trial of tipifarnib in combination with alpelisib in PIK3CA-dependent head and neck squamous cell carcinoma (HNSCC) in the first half of 2025."

P1/2 data • Trial status • Head and Neck Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

FIT-001: A phase 1 clinical trial of the farnesyl transferase inhibitor KO-2806 alone or as part of combination therapy for advanced solid tumors. (ASCO 2024) - P1, P2 | "Recent clinical trials (NCT03719690, NCT02383927) of the FTI, tipifarnib, in patients with HRAS-mutant (HRAS-m) head and neck squamous cell carcinoma harboring high variant allele frequency mutations (VAF ≥20%), showed objective response rates of up to 50% and favorable long-term outcomes...In preclinical studies, KO-2806 has been shown to: (1) enhance tumor growth inhibition of tyrosine kinase inhibitors, including cabozantinib, in multiple clear cell renal cell carcinoma (ccRCC) cell line- and patient-derived xenograft models; and (2) enhance activity of KRAS inhibitors, including adagrasib, in KRAS mutant non-small cell lung cancer (NSCLC), colorectal cancer (CRC), and pancreatic ductal adenocarcinoma (PDAC) mouse models...Other combination arms may also be considered. The study began accrual in October 2023."

Clinical • Combination therapy • IO biomarker • Metastases • P1 data • Clear Cell Renal Cell Carcinoma • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • HRAS • KRAS

Kura Oncology Reports First Quarter 2024 Financial Results (GlobeNewswire) - "Forecasted Milestones: (i) Initiate Phase 1b expansion study of ziftomenib in combination with standards of care, including venetoclax/azacitidine in newly diagnosed NPM1-mutant or KMT2A-rearranged AML, in the second half of 2024; (ii) Submit an investigational new drug application for ziftomenib in a solid tumor indication and present preclinical data at a medical meeting in the second half of 2024; (iii) Dose the first patients with KO-2806 and adagrasib in KRASG12C-mutated non-small cell lung cancer by mid-2024."

IND • New P1 trial • Preclinical • Trial status • Acute Myelogenous Leukemia • Non Small Cell Lung Cancer • Solid Tumor

FIT-001: A phase 1 clinical trial of the farnesyl transferase inhibitor KO-2806 alone or as part of combination therapy for advanced solid tumors (AACR 2024) - P1, P2 | "Recent clinical trials (NCT03719690, NCT02383927) of the FTI, tipifarnib, in patients with HRAS-mutant (HRAS-m) head and neck squamous cell carcinoma harboring high variant allele frequency mutations (VAF ≥20%), showed objective response rates of up to 50% and favorable long-term outcomes...In preclinical studies, KO-2806 has been shown to: (1) enhance tumor growth inhibition of tyrosine kinase inhibitors, including cabozantinib, in multiple clear cell renal cell carcinoma (ccRCC) cell line- and patient-derived xenograft models; and (2) enhance activity of KRAS inhibitors, including adagrasib, in KRAS mutant non-small cell lung cancer (NSCLC), colorectal cancer (CRC), and pancreatic ductal adenocarcinoma (PDAC) mouse models...Other combination arms may also be considered. The study began accrual in October 2023."

Clinical • Combination therapy • IO biomarker • Metastases • P1 data • Clear Cell Renal Cell Carcinoma • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • HRAS • KRAS

Kura Oncology Reports Fourth Quarter and Full Year 2023 Financial Results (GlobeNewswire) - "Forecasted Milestones:...(i) Dose the first patients in the FIT-001 dose-escalation trial of KO-2806 in combination with cabozantinib in ccRCC by mid-2024; (ii) Dose the first patients in the FIT-001 dose-escalation trial of KO-2806 in combination with adagrasib in KRASG12C-mutated NSCLC by mid-2024; (iii) Complete enrollment of two expansion cohorts to support determination of the optimal biologically active dose for tipifarnib in combination with alpelisib by the end of 2024."

Trial status • Clear Cell Renal Cell Carcinoma • Non Small Cell Lung Cancer • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Kura Oncology Reports First Patient Dosed in Trial of KO-2806 Plus Cabozantinib in Renal Cell Carcinoma (GlobeNewswire) - "Kura Oncology...announced dosing of the first patient with KO-2806, the Company’s next-generation farnesyl transferase inhibitor (FTI), in combination with the tyrosine kinase inhibitor (TKI) cabozantinib in the clear cell renal cell carcinoma (ccRCC) cohort of the Phase 1 portion of the FIT-001 trial....FIT-001 is a first-in-human, multicenter, open-label study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary antitumor activity of KO-2806 when administered as monotherapy and in combination with targeted therapies....The Company expects to begin dosing in combination with adagrasib in KRASG12C-mutant non-small cell lung cancer (NSCLC) next quarter."

Trial status • Clear Cell Renal Cell Carcinoma • Non Small Cell Lung Cancer