IK-595 for Cancer

Recruiting at 16 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

150 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug IK-595 for cancer treatment?

Research on similar treatments shows that targeting integrins and using MEK inhibitors can enhance anticancer effects, as seen in studies where integrin-targeted therapies improved the effectiveness of cancer drugs and inhibited tumor growth. ^{1 2 3 4 5}

What makes the drug IK-595 unique for cancer treatment?

IK-595 is unique because it acts as a MEK/RAF molecular glue, which means it helps bring together specific proteins to inhibit cancer cell growth, unlike traditional treatments that often target these proteins separately. ^{6 7 8 9 10}

What is the purpose of this trial?

This is a Phase 1, FIH, Dose Escalation and Dose Expansion study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) effects, and preliminary antitumor activity of 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 for whom there are no further treatment options known to confer clinical benefit.

Research Team

Caroline Germa, MD

Principal Investigator

Ikena Oncology

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

1. Switzerland 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. [2020]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Synthesis and biological evaluation of RGD-conjugated MEK1/2 kinase inhibitors for integrin-targeted cancer therapy. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Integrin-linked kinase inhibitor KP-392 demonstrates clinical benefits in an orthotopic human non-small cell lung cancer model. [2021]

4. Germany pubmed.ncbi.nlm.nih.gov

Immunoreactivity of integrin-linked kinase in primary non-small-cell lung cancer and survival after curative resection. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Pharmacological inhibition of EGFR tyrosine kinase affects ILK-mediated cellular radiosensitization in vitro. [2021]

6. United States 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. [2015]

7. United States pubmed.ncbi.nlm.nih.gov

MK-2461, a novel multitargeted kinase inhibitor, preferentially inhibits the activated c-Met receptor. [2010]

8. United States 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. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Signaling threshold regulation by the Ras effector IMP. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

IMP modulates KSR1-dependent multivalent complex formation to specify ERK1/2 pathway activation and response thresholds. [2021]