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

The KRAS targeting revolution in metastatic pancreatic cancer: insights from the landmark RASolute-302 trial and emerging allele-specific strategies at ASCO 2026. (PubMed, J Hematol Oncol) - "This correspondence highlights how the first-in-class pan-RAS (ON) inhibitor daraxonrasib (RMC-6236) virtually doubled median overall survival (13.2 vs. 6.6 months) and progression-free survival compared to chemotherapy in second-line mPDAC, establishing a new standard of care...These include the selective KRAS G12D inhibitor DN022150 and promising horizontal combinations pairing the G12D inhibitor HRS-4642 with either the anti-PD-L1 antibody adebrelimab or a Nectin-4-targeted antibody-drug conjugate (ADC). Furthermore, we address the KRAS G12C cohort where farnesyl transferase co-inhibition (darlifarnib plus adagrasib) successfully bypasses adaptive resistance. Ultimately, the therapeutic landscape of mPDAC is transitioning toward tailored genomic frameworks. Future success will rely on optimizing the clinical sequencing or combination of pan-RAS and allele-specific agents, guided by real-time liquid biopsies, to permanently dismantle resistance and transform mPDAC into..."

IO biomarker • Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • KRAS

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 • First-in-human • 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

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

Farnesyl transferase inhibitor (FTI) darlifarnib (KO-2806) in combination with adagrasib in KRAS G12C mutated (mut) advanced solid tumors: Preliminary results from the FIT-001 phase 1 first-in-human trial. (ASCO 2026) - P1 | "Darlifarnib 3 and 5 mg + ada were well tolerated with encouraging antitumor activity in heavily pretreated KRAS G12C mut NSCLC, PDAC and CRC. These preliminary data support further investigation of darlifarnib + KRASi, such as ada, to address mTORC1-mediated resistance and potentially improve clinical outcomes for pts. aConfirmed+unconfirmed responses."

Combination therapy • First-in-human • Metastases • P1 data • Hematological Disorders • Lung Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thrombocytopenia • KRAS • RHEB

Darlifarnib – Precision Combination Platform in Solid Tumors (Kura Oncology Press Release) - "Complete enrollment in the randomized FIT-001 Phase 1b study evaluating darlifarnib plus cabozantinib in cabozantinib-naïve ccRCC in 1H 2027 and report initial clinical data in 2H 2027; Initiate a platform study of darlifarnib plus daraxonrasib in patients with KRAS-mutant 2L+ PDAC in 1H 2027."

Enrollment status • New trial • P1 data • Clear Cell Renal Cell Carcinoma • Pancreatic Ductal Adenocarcinoma

Kura Oncology, Inc…announced updated Phase 1a results from the ongoing FIT-001 clinical trial (NCT06026410) demonstrating encouraging and durable clinical activity of darlifarnib plus cabozantinib in cabozantinib-naïve patients with advanced clear cell renal cell carcinoma (ccRCC). (Kura Oncology Press Release) - "Clinical Activity in Cabozantinib-naïve ccRCC Patients (N=34): Objective response rate ranged from 33% to 50% across evaluated darlifarnib dose levels; Median progression free survival was 13 months across pooled dose levels; Median duration of response was not estimable at most dose levels assessed because multiple responses remain ongoing; Durable clinical benefit was observed across all evaluated combination dose levels, with more than half of patients remaining on treatment at data cut-off."

P1 data • Clear Cell Renal Cell Carcinoma

Farnesyl Transferase Inhibitor (FTI) Darlifarnib Combined with Cabozantinib in Renal Cell Carcinoma (RCC): Updated Phase 1a Results from FIT-001 (KCRS 2026) - P1 | "FIT-001 Ph1b is ongoing and enrolling cabozantinib-naive ccRCC patients, with randomization across darlifarnib 5 and 8 mg plus cabozantinib 60 mg and a cabozantinib monotherapy arm, with potential to cross over to a combination arm upon progression. Keywords renal cell carcinoma, darlifarnib, farnesyl transferase inhibitor, cabozantinib, phase 1"

First-in-human • P1 data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Hematological Disorders • Neutropenia • Oncology • Renal Cell Carcinoma • Respiratory Diseases • Solid Tumor • RHEB

Kura Oncology, Inc…announced that updated Phase 1a results from the ongoing FIT-001 Phase 1a/1b clinical trial (NCT06026410) evaluating darlifarnib in combination with cabozantinib in advanced renal cell carcinoma (RCC) will be featured in an oral presentation at the 2026 Kidney Cancer Research Summit (KCRS) in Boston. (The Manila Times) - "The presentation will highlight long-term follow-up results in heavily pretreated cabozantinib-naïve patients with refractory RCC...Kura is currently enrolling patients in the U.S. and E.U. in the randomized Phase 1b dose-optimization portion of FIT-001 in cabozantinib-naïve, refractory, advanced ccRCC. The randomized Phase 1b portion is evaluating darlifarnib plus cabozantinib versus cabozantinib alone and is designed to inform selection of a recommended Phase 3 dose for a registrational study planned for 2028."

New P3 trial • P1 data • Renal Cell Carcinoma

Darlifarnib: Data from P1 FIT-001 trial (NCT06026410) in combination with cabozantinib for clear cell RCC in 2027 (Kura Oncology) - ASCO 2026: Initiation of P3 trial in combination with cabozantinib for 2L/3L clear cell RCC in 2028

New P3 trial • P1 data • Clear Cell Renal Cell Carcinoma • Oncology • Solid Tumor

Darlifarnib: Initiation of registrational trial for 2L+ solid tumors in 2028 (Kura Oncology) - ASCO 2026

New trial • Oncology • Solid Tumor

Darlifarnib + daraxonrasib: Initiation of P1a/b trial in KRAS mutant cancers in early 2027 (Kura Oncology) - ASCO 2026

New P1 trial • Oncology • Solid Tumor

Darlifarnib: “Darlifarnib + adagrasib was well tolerated with manageable safety profile”; Solid tumors (Kura Oncology) - ASCO 2026

P1 data • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Kura Oncology Reports Strong Clinical Activity and Safety with Darlifarnib + Adagrasib in KRAS G12C-Mutated Solid Tumors (Kura Oncology Press Release) - "The combination of darlifarnib plus adagrasib demonstrated meaningful antitumor activity in heavily pretreated pancreatic ductal adenocarcinoma (PDAC) and non-small cell lung cancer (NSCLC) patients with prior KRAS inhibitor (KRASi) exposure, as well as KRASi-naive colorectal cancer (CRC) patients...77% (20/26) of response-evaluable patients achieved tumor shrinkage, including 94% (15/16) of response-evaluable, KRASi-naïve patients; Objective response rate (ORR): 67% in PDAC, 50% in NSCLC, and 29% in KRASi-naïve CRC; Median follow-up time (range): PDAC 6.7 (4.0-10.4) months; NSCLC 6.9 (3.2-11.8) months; CRC 8.9 (1.2-13.2) months"

P1 data • Colorectal Cancer • Non Small Cell Lung Cancer • Pancreatic Ductal Adenocarcinoma

2026 Commercial Priorities and Anticipated Development Milestones:…Darlifarnib (GlobeNewswire) - "(i) Present preliminary clinical data for darlifarnib plus adagrasib in KRASG12C-mutated solid tumors at the upcoming American Society of Clinical Oncology (ASCO) 2026 Annual Meeting in May 2026; (ii) Present updated Phase 1a data with the first report of long-term follow-up for darlifarnib plus cabozantinib in advanced RCC (2H 2026)."

P1 data • Renal Cell Carcinoma • Solid Tumor

Farnesyl transferase inhibitor (FTI) darlifarnib (KO-2806) combined with cabozantinib (cabo) in clear cell renal cell carcinoma (ccRCC) patients after prior exposure to cabo: Preliminary phase 1 results from FIT-001 (NCT06026410) (EIKCS 2026) - P1 | "This combination demonstrated a manageable safety profile and promising antitumor activity in ccRCC patients with prior cabo exposure. Activity of the combination in a post-cabo setting is suggestive of darlifarnib's contribution to antitumor activity in this underserved patient population. These data support further development of darlifarnib and cabo in ccRCC."

Clinical • P1 data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer

Kura Oncology Reports Darlifarnib Plus Cabozantinib Demonstrates Robust Activity in Patients With Clear Cell Renal Cell Carcinoma Previously Treated With Cabozantinib (GlobeNewswire) - "Objective response rate (ORR) was 44%, with a disease control rate (DCR) of 94% across all doses tested in this population; Tumor shrinkage observed in 75% of patients, with reductions ranging from 32% to 47% among responders; Antitumor activity observed in a heavily pre-treated, cabozantinib-exposed population, including patients whose best response to prior cabozantinib was stable disease; Responses observed in patients previously treated with cabozantinib in the immediate prior line as well as those who had received other TKIs in addition to cabozantinib."

P1 data • Clear Cell Renal Cell Carcinoma

FIT-001: KO-2806 Monotherapy and Combination Therapies in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=300 | Recruiting | Sponsor: Kura Oncology, Inc. | N=66 ➔ 300

Enrollment change • First-in-human • Monotherapy • Clear Cell Renal Cell Carcinoma • Colorectal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Kidney Cancer • Lung Cancer • Non Clear Cell Renal Cell Carcinoma • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • HRAS • KRAS • NRAS

2026 Strategic Priorities and Anticipated Milestones: Darlifarnib (Kura Oncology Press Release) - "Present preliminary clinical data for darlifarnib plus adagrasib in KRASG12C-mutated solid tumors (1H 2026); Present updated Phase 1a data with ~ 1 year of additional follow-up for darlifarnib plus cabozantinib in advanced RCC (2H 2026)."

P1 data • Clear Cell Renal Cell Carcinoma • Colorectal Cancer • Non Clear Cell Renal Cell Carcinoma • Pancreatic Ductal Adenocarcinoma

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…announced it will present updated data from its ongoing FIT-001 clinical trial (NCT06026410) evaluating darlifarnib (KO-2806) in combination with cabozantinib in patients with advanced clear cell renal cell carcinoma at the International Kidney Cancer Symposium (IKCS) Europe 2026 (GlobeNewswire) - "The data to be presented build on earlier findings from the FIT-001 study reported at the 2025 European Society for Medical Oncology (ESMO) Congress, where the combination of darlifarnib and cabozantinib demonstrated encouraging clinical activity and a manageable safety profile in patients with advanced renal cell carcinoma."

P1 data • Clear Cell Renal Cell Carcinoma

Farnesyl transferase inhibitor KO-2806 (darlifarnib) enhances the anti-tumor activity of tyrosine kinase inhibitors in RCC. (PubMed, Mol Cancer Ther) - "This translates to tumor regressions and robust inhibition of tumor neovascularization in preclinical models of RCC exposed to the combination of anti-VEGFR TKIs and KO-2806. KO-2806 also sensitizes tumors previously progressing on anti-VEGFR TKIs, suggesting potential benefits of KO-2806 as a combination partner across the treatment continuum in RCC."

Journal • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

The farnesyl transferase inhibitor darlifarnib (KO-2806) re-sensitizes relapsing tumors to RAS inhibition. (PubMed, Cancer Res) - "Further, the addition of KO-2806 rescued sensitivity of progressing tumors to the pan-RAS inhibitor RMC-6236. These results establish mTORC1 as an important mediator of escape from RAS inhibition and highlight KO-2806 as a promising RAS companion inhibitor in patients with prior RAS inhibitor exposure."

Journal • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS • RHEB

Expected 2026 Key Milestones:…Darlifarnib Development (GlobeNewswire) - "(i) Initiate expansion cohorts of darlifarnib and cabozantinib in advanced renal cell carcinoma (RCC) (Phase 1b) in the first half of 2026; (ii) Present preliminary data from darlifarnib and adagrasib in KRASG12C-mutated solid tumors (non-small cell lung cancer, colorectal cancer, pancreatic ductal adenocarcinoma) in the first half of 2026; (iii) Present updated dose-escalation data from darlifarnib and cabozantinib in advanced RCC (Phase 1a) in the second half of 2026; (iv) Explore opportunities to evaluate additional indications and combination agents in 2026."

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

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