IK-595 for Cancer

No longer recruiting at 18 trial locations

Overseen By Trupti Lingaraj

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Ikena Oncology

Must not be taking: Corticosteroids, Antineoplastics

Disqualifiers: CNS lesions, Cardiovascular disease, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called IK-595 (a MEK/RAF molecular glue) for individuals with advanced solid tumors that have specific genetic changes in the RAS-MAPK pathway. The primary goal is to assess the drug's safety and tolerability while gathering preliminary data on its cancer-fighting potential. Suitable candidates have advanced or metastatic solid tumors with no remaining treatment options and specific gene alterations such as NRAS, KRAS, or BRAF mutations. Participants must be able to take oral medication and have recovered from previous cancer treatments. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does exclude patients taking any medication on the prohibited list unless they can switch to other medications. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that IK-595 is likely to be safe for humans?

Research has shown that IK-595 is being tested for safety and patient tolerance in those with advanced solid tumors. Early results from previous studies suggest that IK-595, a MEK/RAF molecular glue, blocks certain proteins that aid cancer cell growth.

As a Phase 1 study, the primary goal is to assess the treatment's safety and how patients handle any side effects. Phase 1 trials typically involve a small number of participants and help researchers determine the safest dose. Detailed information about specific side effects of IK-595 is not yet available, as this is an early stage of testing. However, the study will closely monitor participants for any negative effects to ensure their safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard cancer treatments that often include chemotherapy, radiation, or targeted therapies, IK-595 is unique because it involves a novel mechanism of action. Researchers are excited about IK-595 because it targets cancer cells in a way that could potentially reduce side effects and improve outcomes compared to traditional treatments. This new approach may offer hope for patients who have not responded well to existing therapies, providing a fresh avenue for effective treatment.

What evidence suggests that IK-595 might be an effective treatment for cancer?

Research has shown that IK-595, a new treatment under study in this trial, holds promise for treating advanced solid tumors with specific genetic changes. It works by inactivating a protein called MEK, which halts signals that promote tumor growth. In previous studies, this method helped control the disease in more than half of the patients tested. Its effectiveness has been observed in various cancer types, particularly those with genetic changes known as RAS/RAF alterations. This suggests that IK-595 could be a potential option for patients with limited treatment choices. ^{4 6 7 8 9}

Who Is on the Research Team?

Caroline Germa, MD

Principal Investigator

Ikena Oncology

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors that have specific gene changes in the RAS-MAPK pathway, such as certain types of cancer including thyroid, melanoma, pancreatic, lung, brain and colorectal cancers. Participants must have no remaining treatment options known to help them.

Inclusion Criteria

My blood counts and organ functions are within normal ranges, and I have recovered from previous cancer treatments.

I have an advanced cancer that cannot be surgically removed and no other treatments are expected to help.

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

I have a serious heart condition.

I do not have any severe illnesses that are not under control.

I am not on any cancer treatment except for symptom relief radiation or specific hormonal therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Initial phase to evaluate safety, tolerability, and determine the maximum tolerated dose using a Bayesian Optimal Interval design

Approximately 1 year

Dose Expansion

Phase to further evaluate safety and preliminary antitumor activity in genetically/molecularly defined cohorts

Approximately 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• IK-595

Trial Overview The study tests IK-595 taken orally. It's a Phase 1 trial aiming to find out how safe it is and how well people can tolerate it. The drug's effects on the body (pharmacokinetics) and tumor response are also being studied.

How Is the Trial Designed?

Group I: IK-595 Experimental Treatment 1 Intervention

Dose Escalation and Dose Expansion

Who Is Running the Clinical Trial?

Ikena Oncology

Lead Sponsor

Trials

6

Recruited

510+

Published Research Related to This Trial

MK-2461 is a novel inhibitor that effectively targets activated c-Met, showing strong potency in blocking its phosphorylation in various cancer cell lines, particularly those with genomic amplifications of MET or FGFR2.

In a murine xenograft model of gastric cancer, MK-2461 demonstrated significant tumor growth suppression with a well-tolerated oral dosage, indicating its potential as a safe and effective cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MK-2461, a novel multitargeted kinase inhibitor, preferentially inhibits the activated c-Met receptor. Pan, BS., Chan, GK., Chenard, M., et al.[2010]

The ILK inhibitor KP-392 significantly improved survival rates in a metastatic lung cancer model when used alone (34.9 days) and even more so in combination with cisplatin (45.8 days), compared to control (30.2 days).

KP-392 was well tolerated and did not increase the toxicity of cisplatin, suggesting it could be a safe and effective addition to lung cancer treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integrin-linked kinase inhibitor KP-392 demonstrates clinical benefits in an orthotopic human non-small cell lung cancer model. Liu, J., Costello, PC., Pham, NA., et al.[2021]

In a study of 138 patients with non-small-cell lung cancer (NSCLC), 64% showed immunoreactivity for integrin-linked kinase (ILK), with higher rates in adenocarcinoma compared to squamous cell carcinoma (SCC).

ILK positivity in SCC was linked to significantly shorter 5-year cancer-related survival (42% vs. 72%) and recurrence-free survival (38% vs. 60%) compared to ILK-negative patients, indicating that ILK expression is a critical adverse prognostic factor in this subtype.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunoreactivity of integrin-linked kinase in primary non-small-cell lung cancer and survival after curative resection. Watzka, SB., Rauscher-Pötsch, I., Stubenberger, E., et al.[2021]

IMP acts as a regulatory resistor in the Raf-MEK-ERK signaling pathway, controlling how signals are transmitted by modulating the assembly of Raf-MEK complexes.

By inhibiting the function of KSR, a key protein in this pathway, IMP helps to prevent excessive activation of the Raf-MEK pathway, thereby maintaining proper cellular signaling balance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Signaling threshold regulation by the Ras effector IMP. Matheny, SA., White, MA.[2021]

IMP acts as a regulatory protein that inhibits the signaling pathway from Raf to MEK by disrupting the formation of essential protein complexes, which is crucial for proper kinase activation.

The study reveals that IMP's ability to modulate signal strength is linked to its interference with KSR1 and Raf oligomerization, highlighting its role in controlling cellular responses to Ras signaling.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IMP modulates KSR1-dependent multivalent complex formation to specify ERK1/2 pathway activation and response thresholds. Chen, C., Lewis, RE., White, MA.[2021]

The novel RGD-MEKI conjugates, particularly RGD-PD0325901, showed significantly enhanced anti-tumor properties by effectively inhibiting the ERK pathway and DNA replication in cancer cells, outperforming the original PD0325901 in U87 cell assays.

PEGylation and the use of multi-cRGD peptide cargo improved the targeting and anti-proliferation activity of these conjugates, indicating a promising approach for integrin receptor-mediated anticancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and biological evaluation of RGD-conjugated MEK1/2 kinase inhibitors for integrin-targeted cancer therapy. Li, X., Hou, J., Wang, C., et al.[2021]

Integrin-linked kinase (ILK) enhances radiosensitivity in cancer cells, as shown in human FaDu squamous cell carcinoma cells, where hyperactive ILK led to significantly reduced survival after radiation compared to controls.

The effectiveness of ILK-mediated radiosensitization relies on the activity of the epidermal growth factor receptor (EGFR) tyrosine kinase; inhibiting EGFR reduced the radiosensitizing effect of ILK, indicating a critical link between these pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological inhibition of EGFR tyrosine kinase affects ILK-mediated cellular radiosensitization in vitro. Eke, I., Sandfort, V., Storch, K., et al.[2021]

Simalikalactone E (SkE) effectively inhibits the growth of various leukemia and solid tumor cell lines, particularly showing strong efficacy against chronic myelogenous leukemia (CML) cells by impairing the MAPK pathway.

SkE is particularly potent against melanoma cells with the B-Raf-V600E mutation, resensitizing resistant melanoma cell lines and demonstrating similar effectiveness to imatinib in reducing tumor formation in a mouse model of CML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simalikalactone E (SkE), a new weapon in the armamentarium of drugs targeting cancers that exhibit constitutive activation of the ERK pathway. Robert, G., Jullian, V., Jacquel, A., et al.[2021]

CH4987655, a selective MEK inhibitor, was found to be safe and well tolerated in a study of 40 healthy subjects, with no severe adverse events reported and only mild to moderate side effects observed.

The drug effectively inhibited pERK levels in a dose-dependent manner, achieving over 80% inhibition at higher doses, indicating its potential efficacy in targeting tumor growth through the MAPK signaling pathway.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety, tolerability, pharmacokinetics, and pharmacodynamics of single oral doses of CH4987655 in healthy volunteers: target suppression using a biomarker. Lee, L., Niu, H., Rueger, R., et al.[2015]

A novel drug conjugate targeting integrin αVβ3 and linked to the tyrosine kinase inhibitor sunitinib showed significant antitumor effects in both cisplatin-sensitive and -resistant ovarian carcinoma cells, indicating its potential effectiveness against drug-resistant tumors.

In animal studies, this conjugate demonstrated superior antitumor activity compared to sunitinib alone, suggesting that integrin-targeted therapies could enhance treatment outcomes for patients with ovarian carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of a Selective Binder of αVβ3 Integrin Linked to the Tyrosine Kinase Inhibitor Sunitinib in Ovarian Carcinoma Preclinical Models. Sartori, A., Corno, C., De Cesare, M., et al.[2020]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.3100

SPYK04, a novel RAF-MEK molecular glue: Dose ... The disease control rate (DCR; PR+SD) was 52.2% (n = 12 of 23). Conclusions: SPYK04 was tolerated at doses up to 1.3 mg/day in patients with ...

2. cancer.gov cancer.gov/clinicaltrials/NCI-2024-06144

Study of IK-595 in RAS- or RAF-altered Advanced Tumors IK-595, a MEK/RAF molecular glue, administered orally as monotherapy in patients with advanced solid tumors with gene alterations in the RAS- MAPK pathway.

3. researchgate.net researchgate.net/publication/391188864_Abstract_CT268_Preliminary_results_from_a_first-in-human_study_of_IK-595_an_oral_MEKRAF_molecular_glue_in_patients_with_RAS-_or_RAF-altered_advanced_solid_tumors

Preliminary results from a first-in-human study of IK-595, an ... IK-595, a novel MEK-RAF molecular glue, traps MEK in an inactive complex with all RAF isoforms and durably blocks MEK and ERK phosphorylation.

4. meetings.asco.org meetings.asco.org/abstracts-presentations/238370

A first-in-human study of IK-595, an oral MEK/RAF ... IK-595 exhibits potent single agent activity in a wide range of in vivo cancer models harboring various RAS/RAF alterations, including, but not limited to, lung ...

5. withpower.com withpower.com/trial/phase-1-carcinoma-11-2023-9a856

IK-595 for Cancer · Info for Participants The ILK inhibitor KP-392 significantly improved survival rates in a metastatic lung cancer model when used alone (34.9 days) and even more so in combination ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS3185

A first-in-human study of IK-595, an oral MEK/RAF ... This is a phase 1, first-in-human, open-label, multicenter study to evaluate IK-595 as monotherapy in patients with RAS- or RAF-altered advanced solid tumors.

7. aacrjournals.org aacrjournals.org/cancerres/article/85/8_Supplement_2/CT268/761472/Abstract-CT268-Preliminary-results-from-a-first-in

Preliminary results from a first-in-human study of IK-595, an ... IK-595, a novel MEK-RAF molecular glue, traps MEK in an inactive complex with all RAF isoforms and durably blocks MEK and ERK phosphorylation.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06270082

NCT06270082 | Study of IK-595 in RAS- or RAF-altered ... This is a Phase 1, FiH clinical study to evaluate the safety, tolerability, PK and pharmacodynamic effects, and preliminary anti-tumor activity of IK-595.

9. ikenaoncology.com ikenaoncology.com/scientific-publication/ik-595-a-best-in-class-mek-raf-molecular-glue-drives-broad-and-potent-anti-tumor-activity-across-ras-mapk-pathway-altered-cancers-as-a-monotherapy-and-in-combination/

IK-595, a best-in-class MEK-RAF molecular glue, drives ... IK-595, a best-in-class MEK-RAF molecular glue, drives broad and potent anti-tumor activity across RAS/MAPK pathway-altered cancers as a monotherapy and in ...