KO-2806 + Cabozantinib for Solid Cancers

(FIT-001 Trial)

Recruiting at 33 trial locations

Overseen By Clinical Operations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Kura Oncology, Inc.

Must not be taking: Anticancer agents, FTI, HRAS inhibitors

Disqualifiers: CNS metastases, Autoimmune disorders, Infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

270 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores KO-2806, a new treatment for individuals with advanced solid tumors, which develop in solid organs or tissues. The trial tests KO-2806 alone and in combination with another drug, Cabozantinib, in different groups. It specifically seeks participants with certain tumor types, such as HRAS-mutant tumors or KRAS G12C-mutant cancers, who have already undergone other treatments. Individuals with advanced solid tumors who have previously received treatment might be suitable for this trial. As a Phase 1 trial, this research aims to understand how KO-2806 works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial excludes participants who are currently on certain anticancer treatments, so you may need to stop taking those specific medications. However, the protocol does not specify all medications that must be stopped, so it's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that KO-2806 is being tested for safety in humans in a new study. As this is its first test in people, information on its tolerance is limited. However, the study closely monitors safety and any possible side effects.

The trial also tests KO-2806 with cabozantinib, a drug already used to treat some cancers. Cabozantinib is known to be safe, as it is FDA-approved for other conditions. While KO-2806 is new, combining it with cabozantinib might be safer because much is already known about cabozantinib.

Researchers closely monitor participants to observe how their bodies react, which helps quickly identify and address any unwanted effects. Although the trial is in its early stages, the main goal is to ensure the treatment is as safe as possible for participants. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about KO-2806 combined with cabozantinib because it offers a fresh approach to tackling solid tumors with RAS alterations. Unlike standard treatments that might not specifically target RAS mutations, KO-2806 is designed to target these mutations directly, potentially offering a more precise attack on cancer cells. This is particularly promising for patients with hard-to-treat cancers like HRAS, KRAS, and NRAS mutations, which can be resistant to conventional therapies. By focusing on these specific genetic alterations, KO-2806 could provide a new avenue for treatment where existing options, like chemotherapy or immunotherapy, may fall short.

What evidence suggests that this trial's treatments could be effective for advanced solid tumors?

This trial will evaluate the combination of KO-2806 and Cabozantinib for treating solid tumors. Research has shown that KO-2806, a drug targeting specific proteins in cancer cells, may help treat solid tumors with RAS changes. Laboratory studies found that KO-2806 can enhance the effectiveness of Cabozantinib, an approved cancer drug, in stopping tumor growth. In this trial, one arm will focus on patients with RAS-altered advanced solid tumors, while another will include patients with advanced or metastatic renal cell carcinoma (RCC). A third arm will study patients with advanced or metastatic non-small cell lung cancer (NSCLC), colorectal cancer (CRC), or pancreatic ductal adenocarcinoma (PDAC) with the KRAS G12C mutation. Overall, these findings suggest that combining KO-2806 with Cabozantinib could be a promising approach for treating certain advanced cancers. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

Adults with advanced solid tumors, including specific types of colorectal, pancreatic, renal cell carcinoma, and non-small cell lung cancer. Participants must be over 18 with acceptable organ function and measurable disease. Some groups require prior treatments or certain genetic features in their tumors.

Inclusion Criteria

I have had at least one treatment for advanced kidney cancer that included immunotherapy.

My liver, kidneys, hormone levels, and blood counts are all within normal ranges.

My cancer is confirmed to be advanced through testing.

Exclusion Criteria

I am currently on cancer treatment medication.

I have previously been treated with an FTI or HRAS inhibitor.

I haven't had major surgery in the last 28 days or I've fully recovered from it.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of KO-2806 to assess safety and tolerability

28 days per cycle

Multiple visits per cycle

Dose Expansion

Participants receive validated doses of KO-2806 to further assess efficacy and safety

28 days per cycle, up to 24 months

Multiple visits per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

28 days after last dose

What Are the Treatments Tested in This Trial?

Interventions

• Cabozantinib
• KO-2806

Trial Overview KO-2806 is being tested both alone and combined with Cabozantinib to see how well it works for treating various advanced solid tumors. The trial will gradually increase doses to find the safest and most effective levels.

How Is the Trial Designed?

Group I: Arm #3: Advanced or metastatic NSCLC, CRC, or PDAC Experimental Treatment 2 Interventions

Patients with KRAS G12C-mutant locally advanced or metastatic NSCLC, CRC, or PDAC who have received at least 1 prior systemic therapy including available approved standard of care treatments

Group II: Arm #2: Advanced or metastatic RCC Experimental Treatment 2 Interventions

Patients who have received at least 1 prior systemic therapy with IO-based treatment for locally advanced or metastatic RCC with predominantly clear cell subtype; non-clear cell RCC patients who are either treatment naïve or have received any prior systemic treatment for locally advanced and metastatic RCC

Group III: Arm #1: RAS-altered advanced solid tumors Experimental Treatment 1 Intervention

Patients with advanced solid tumors and the following: * HRAS-mutant and/or amplified tumors (any solid tumor type) * HRAS overexpression (only for HNSCC tumors) * KRAS and/or NRAS and/or HRAS-mutant and/or amplified for NSCLC or CRC * KRAS-mutant and/or amplified PDAC

Who Is Running the Clinical Trial?

Kura Oncology, Inc.

Lead Sponsor

Trials

19

Recruited

1,700+

Mirati Therapeutics Inc.

Industry Sponsor

Trials

73

Recruited

8,900+

Dr. Charles M. Baum

Mirati Therapeutics Inc.

Chief Executive Officer since 2023

MD, PhD

Dr. Joseph Leveque

Mirati Therapeutics Inc.

Chief Medical Officer since 2021

MD

Published Research Related to This Trial

In a phase Ib/II study involving 64 patients with progressive non-small cell lung cancer (NSCLC) who had previously received erlotinib, cabozantinib alone showed a modest objective response rate (ORR) of 8.2%, indicating some efficacy as a treatment option.

However, in the phase II portion, the combination of cabozantinib and erlotinib did not yield any responses in patients with acquired resistance to erlotinib, suggesting that cabozantinib did not effectively re-sensitize these patients to erlotinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase Ib/II study of cabozantinib (XL184) with or without erlotinib in patients with non-small cell lung cancer. Wakelee, HA., Gettinger, S., Engelman, J., et al.[2023]

Cabozantinib (CAB) has shown significant improvements in overall survival and progression-free survival in phase-III studies for patients with advanced renal cell carcinoma and hepatocellular carcinoma, leading to its approval in Japan for these conditions.

CAB may enhance antitumor immunity and, when combined with PD-1 checkpoint inhibitors like nivolumab, has demonstrated increased progression-free survival compared to standard treatments, indicating a potential synergistic effect in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacological properties and clinical outcomes of the anti-cancer drug, cabozantinib (CABOMETYX®)]. Osaka, T., Yamaguchi, N., Hara, T.[2022]

Cabozantinib shows promising anti-tumor activity in patients with metastatic clear cell renal cell carcinoma (RCC), with a partial response observed in 28% of the 25 heavily pretreated participants.

The treatment demonstrated a median progression-free survival of 12.9 months and a median overall survival of 15.0 months, with a safety profile consistent with other similar therapies, indicating its potential as a viable option for advanced RCC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of cabozantinib (XL184) in patients with renal cell cancer. Choueiri, TK., Pal, SK., McDermott, DF., et al.[2021]

Cabozantinib demonstrated significant anticancer activity, particularly in ovarian cancer (21.7% objective response rate) and castration-resistant prostate cancer, which showed a median progression-free survival of 5.5 months compared to 1.4 months for placebo.

The trial involved 526 patients, and while cabozantinib showed promising efficacy, nearly half of the patients (48.7%) required dose reductions due to adverse events, with common severe side effects including fatigue, diarrhea, and hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II randomised discontinuation trial of cabozantinib in patients with advanced solid tumours. Schöffski, P., Gordon, M., Smith, DC., et al.[2018]

Cabozantinib showed clinical activity in metastatic breast cancer patients, with an objective response rate of 13.6% and a disease control rate of 46.7% after a 12-week treatment period.

The median progression-free survival was 4.3 months and median overall survival was 11.4 months, indicating that cabozantinib can provide meaningful benefits even in patients with advanced disease who have undergone multiple prior treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabozantinib for metastatic breast carcinoma: results of a phase II placebo-controlled randomized discontinuation study. Tolaney, SM., Nechushtan, H., Ron, IG., et al.[2018]

In a study involving 111 patients with recurrent ovarian cancer, cabozantinib showed a median progression-free survival (PFS) of 5.3 months, which was similar to the 5.5 months achieved with weekly paclitaxel, indicating comparable initial treatment effectiveness.

However, cabozantinib had worse outcomes in overall survival (OS), event-free survival (EFS), and overall response rate (ORR) compared to paclitaxel, along with increased gastrointestinal side effects, leading to the conclusion that cabozantinib is not recommended for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized phase II study of cabozantinib versus weekly paclitaxel in the treatment of persistent or recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer: An NRG Oncology/Gynecologic Oncology Group study. Matulonis, UA., Sill, MW., Makker, V., et al.[2020]

The AXL/GAS6 scoring system, developed from a large-scale immunogenomic analysis of renal cell carcinoma (RCC), can effectively predict prognosis in clear cell RCC, indicating its potential as a robust biomarker.

High AXL/GAS6 scores are associated with an immunosuppressive tumor environment and distinct genomic alterations, particularly in the PI3K-mTOR pathway, highlighting the importance of the AXL/GAS6 axis in RCC progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Landscape of prognostic signatures and immunogenomics of the AXL/GAS6 axis in renal cell carcinoma. Hakozaki, K., Tanaka, N., Takamatsu, K., et al.[2022]

In a phase 3 trial involving 658 patients with metastatic renal-cell carcinoma, cabozantinib significantly improved progression-free survival (7.4 months) compared to everolimus (3.8 months), indicating its greater efficacy after VEGFR-targeted therapy.

Cabozantinib also showed a higher objective response rate (21% vs. 5% for everolimus) and a lower risk of progression or death (42% reduction), although both treatments had similar rates of treatment discontinuation due to adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma. Choueiri, TK., Escudier, B., Powles, T., et al.[2022]

In a Phase 1 study involving 12 patients with relapsed osteosarcoma and Ewing sarcoma, the combination of cabozantinib, topotecan, and cyclophosphamide showed acceptable toxicity levels, with manageable dose-limiting toxicities observed.

The treatment resulted in one partial response and stable disease in seven patients, suggesting that this combination therapy may provide potential disease control in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 study of cabozantinib in combination with topotecan-cyclophosphamide for patients with relapsed Ewing sarcoma or osteosarcoma. Campbell, K., Posner, A., Chen, N., et al.[2023]

Citations

1. kcrs.kidneycan.org kcrs.kidneycan.org/wp-content/uploads/2025/07/70_KCRS-2025-FIT-001-Ayanambakkam.pdf

FIT-001 (NCT06026410): A phase 1 clinical trial of the ... FIT-001 is assessing the safety, tolerability, PK, PD, and preliminary antitumor activity of KO-2806 in combination with cabozantinib in ...

2. ir.kuraoncology.com ir.kuraoncology.com/news-releases/news-release-details/kura-oncology-reports-first-patient-dosed-trial-ko-2806-plus

Kura Oncology Reports First Patient Dosed in Trial of KO- ... Kura is also evaluating KO-2806, a next-generation FTI, in a Phase 1 dose-escalation trial as a monotherapy and in combination with cabozantinib in ccRCC and ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06026410

Study Details | NCT06026410 | KO-2806 Monotherapy and ... This first-in-human (FIH) dose-escalation and dose-validation/expansion study will assess KO-2806, a farnesyl transferase inhibitor (FTI), as a monotherapy and ...

4. ir.kuraoncology.com ir.kuraoncology.com/news-releases/news-release-details/kura-oncology-present-new-data-supporting-combination-ko-2806

Press Release New preclinical data supporting the combination of its next-generation farnesyl transferase inhibitor (FTI) KO-2806 with targeted therapies, including KRAS G12 ...

5. synapse.patsnap.com synapse.patsnap.com/article/kura-oncology-to-present-data-on-ko-2806-with-kras-g12c-and-pan-ras-inhibitors

Kura Oncology to Present Data on KO-2806 with KRAS ... This data supports the combination of its innovative farnesyl transferase inhibitor (FTI) KO-2806 with targeted therapies, such as KRASG12C ...

6. ir.kuraoncology.com ir.kuraoncology.com/news-releases/news-release-details/kura-oncology-highlights-preclinical-data-demonstrating

Press Release Combining with cabozantinib or other TKIs positions KO-2806 to address critical gaps in the treatment of renal cell carcinoma (RCC) and ...

7. urologytimes.com urologytimes.com/view/dosing-begins-in-ccrcc-cohort-of-study-assessing-ko-2806

Dosing begins in ccRCC cohort of study assessing KO-2806 The FIT-001 trial is assessing KO-2806 as a monotherapy and in combination with targeted therapies in patients with advanced solid tumors, including ccRCC.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12509833/

70: A phase 1 clinical trial of the farnesyltransferase ... FIT-001 is assessing the safety, tolerability, pharmacokinetics, PD, and preliminary antitumor activity of KO-2806 in combination with cabozantinib in patients ...