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Solid Tumor, AdultPhase 1NCT06270082

Study of IK-595 in RAS- or RAF-altered Advanced Tumors

A Phase 1 study testing IK-595 in people with Solid Tumor, Adult and Colorectal Cancer, run by Ikena Oncology at 15 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
IK-595
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
75 participants
Where
15 sitesUnited States
Study dates
18 Dec 2023to 8 Sep 2025
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients ≥ 18 years of age.
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
  • Adequate organ function as follows (specimens must be collected during the Screening Period within 7 days prior to entering the Treatment Period):
  • ANC ≥ 1000/μL
  • Hemoglobin > 9 g/dL
  • Platelet count > 75,000/μL
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  • Calculated creatinine clearance ≥ 60 mL/min (using the Cockcroft-Gault formula or using other formulae per institutional guidelines)
  • Serum total bilirubin ≤ 1.5 × ULN or direct bilirubin ≤ ULN for patients with total bilirubin levels > 1.5 × ULN. Known Gilbert syndrome is allowed if total bilirubin is <3 × ULN
  • AST and ALT ≤ 2.5 × ULN (or ≤ 5 × ULN if liver function abnormalities are due to underlying liver metastases)
  • Coagulation: ≤ 1.5 × ULN unless patient is receiving anticoagulant therapy, as long as prothrombin time, international normalized ratio, or activated partial thromboplastin time is within therapeutic range of intended use of anticoagulants when applicable
  • Left ventricular ejection fraction ≥ 50% by echocardiogram or radionuclide test.
  • Patients must have recovered from the side effects of prior cancer-specific therapy to a minimum of ≥ Grade 1 by NCI-CTCAE version 5.0 criteria or return to baseline. Exceptionally, patients with ≤ Grade 2 neuropathy or other TRAEs may be eligible after discussion with the Sponsor.
  • Washout period since receipt of the last dose of prior anticancer therapy (including other investigational therapy):
  • Checkpoint inhibitors such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), or programmed death ligand 1 (PD-L1) inhibitors: ≥ 4 weeks
  • For all other biologic agents (e.g., antiangiogenics): ≥ 3 weeks or a minimum of their dosing interval if shorter than 3 weeks (e.g., agents administered every 2 weeks would require a 2-week washout period)
  • All other investigational agents: ≥ 4 weeks or ≥ 5 × t1/2, whichever is shorter.
  • If feasible, patients must be willing to consent to the submission of formalin-fixed paraffin-embedded (FFPE) tissue blocks of tumor tissue, preferably from a pretreatment, fresh tumor biopsy. Alternatively, archival tumor FFPE blocks or, ≥ 20 unstained slides of tumor tissue from available archival sources that are < 2 years old are acceptable.
  • Highly effective contraception for both male and female patients from Screening through 5 months after the last dose of study drug if the possibility of conception exists.
  • Patient or their legally acceptable representative must be able and willing to:
  • Provide Institutional Review Board-or Institutional Ethics Committee-approved written informed consent in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal patient care.
  • Comply with the study protocol and with the planned biopsy procedures.
  • Patients must have histologically or cytologically confirmed solid tumor malignancies that are advanced and unresectable, or metastatic with no available therapy known to confer clinical benefit, as evaluated by the treating physician. There is no upper limit on the number of prior lines of anticancer therapy received. Tumors must have confirmed RAS/RAF gene alterations as determined by next-generation sequencing or fluorescence in situ hybridization, as documented by local testing:
  • NRASmut solid tumors, including but not limited to melanoma, CRC, and others
  • KRASmut solid tumors, including but not limited to NSCLC, pancreatic carcinoma, and CRC
  • BRAFmut Class I/II/ III or BRAF fusions solid tumors, including but not limited to melanoma, NSCLC, thyroid carcinoma
  • CRAF-altered solid tumors (mutations and gene fusions)
  • NF1mut solid tumors, including but not limited to nerve sheath tumors, gliomas, malignant melanoma, breast cancer, and others
  • Patients who have measurable or evaluable disease by RECIST 1.1 criteria, as assessed by the Investigator/local radiologist.
  • All patients must have a histological diagnosis of an advanced, unresectable, locally recurrent, or metastatic disease with no available therapy known to confer clinical benefit, as evaluated by the treating physician. There is no upper limit on the number of prior lines of anticancer therapy received.
  • Patients must be enrolled in 1 of the following 4 dose expansion cohorts:
  • Cohort 1: Molecularly confirmed NRASmut CRC as determined by local test results
  • Cohort 2: Molecularly confirmed NRASmut malignant melanoma as determined by local test results
  • Cohort 3 Molecularly confirmed KRASmut NSCLC as determined by local test results
  • Cohort 4: Any solid tumors with molecularly confirmed pathogenic BRAF non-V600X mutations or fusions, or pathogenic CRAF mutations or fusions as determined by local test results
  • Patients must have ≥ 1 measurable lesion per RECIST 1.1 criteria as assessed by the Investigator/local radiologist. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. Exceptionally, patients with tumors that are evaluable but non-measurable per RECIST 1.1 criteria can be enrolled following approval by the Sponsor.

Who cannot join

  • Patients with any active central nervous system (CNS) lesion either symptomatic or radiologically unstable and/or leptomeningeal metastasis. However, patients previously treated for these conditions that have had stable CNS disease (verified with consecutive imaging studies) for > 3 months, are asymptomatic and are not currently taking corticosteroids, or are on stable dose or decreasing of corticosteroids for ≥ 7 days prior to enrollment are eligible.
  • Patients who have not recovered to ≤ Grade 1 or baseline from all AEs due to prior anticancer therapies. Exceptionally, patients with ≤ Grade 2 neuropathy or other TRAEs may be eligible after discussion with the Sponsor.
  • Any other concurrent antineoplastic treatment or investigational agent except for localized radiation therapy for symptom palliation (to be considered nontarget lesions after treatment) and/or hormonal therapy for ductal DCIS/LCIS/Stage 1 breast cancer that has been stable on therapy for ≥ 3 years.
  • Uncontrolled or life-threatening symptomatic concomitant disease (including known symptomatic HIV-positive with an active AIDS-defining opportunistic infection or a current CD4 count < 350 cells/μL; symptomatic active hepatitis B or C checked at screening; or active tuberculosis). Patients with HIV are eligible if:
  • They have received antiretroviral therapy (ART) as clinically indicated for ≥ 4 weeks prior to entering the Treatment Period of the study;
  • They continue on ART as clinically indicated while on study;
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  • CD4 counts and viral loads are monitored per standard of care by a local health care provider.
  • Has received prior radiotherapy for palliation ≤ 2 weeks prior to the first dose of study treatment. Patients must have recovered from all radiation-related toxicities.
  • History of a second malignancy requiring systemic treatment ≤ 3 years prior to enrollment. Patients who have remained cancer-free ≤ 3 years of enrollment are eligible. Patients with history of prior early stage basal/squamous cell skin cancer or noninvasive or in situ cancers that have undergone definitive treatment at any prior time are eligible.
  • Clinically significant cardiovascular disease:
  • Cerebral vascular accident/stroke (< 6 months prior to enrollment)
  • Myocardial infarction (< 6 months prior to enrollment)
  • Unstable angina (< 6 months prior to enrollment)
  • Congestive heart failure (New York Heart Association Classification Class III or IV)
  • The presence of any condition that can increase proarrhythmic risk (e.g., hypokalemia, bradycardia, heart block), including any new, unstable, or serious cardiac arrhythmia requiring medication, or other baseline arrhythmias that might interfere with interpretation of ECGs on study (e.g., bundle branch block).
  • Patients with QT interval corrected by Fridericia's formula (QTcF) > 470 msec for both men and women on screening ECG are excluded. Patients with a bundle branch block must have QT interval corrected for bundle branch block.
  • Patients who are on stable doses of concomitant medication with known prolongation of QTcF if QTcF is > 470 msec.
  • Known previous or current serious ophthalmic disorders, including history of glaucoma, history of retinal vein occlusion (RVO) or current risk factors for RVO, history of retinal pathology or evidence of retinal pathology.
  • Active skin disorder requiring systemic treatment ≤3 months prior to start of study treatment.
  • History of rhabdomyolysis ≤3 months prior to start of study treatment.
  • Patients taking any medication on the prohibited medication list are excluded from the study unless they can be transferred to other medications.
  • Has an active infection requiring systemic therapy.
  • A woman of childbearing potential who has a positive pregnancy test prior to initiating study treatment.
  • Breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the Screening visit through 5 months after the last dose of study treatment.
  • Patients who are unable to swallow or retain oral medication.

Trial locations and contacts

15 sites in 1 country.

15 sites in 1 country

United States15 sites

  • Next Oncology

    Austin, Texas, 78758

  • University of Chicago

    Chicago, Illinois, 60637

  • Sarah Cannon Research Institute at HealthOne

    Denver, Colorado, 80218

  • City of Hope

    Duarte, California, 91010

  • INOVA Schar Cancer Institute

    Fairfax, Virginia, 22031

  • START Midwest

    Grand Rapids, Michigan, 49546

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • University of Miami

    Miami, Florida, 33136

  • Sarah Cannon Research Institute

    Nashville, Tennessee, 37203

  • University of California Irvine

    Orange, California, 92868

  • Thomas Jefferson University

    Philadelphia, Pennsylvania, 19107

  • University of Pittsburgh Medical Center- Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • Next Oncology- San Antonio

    San Antonio, Texas, 78229

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Johns Hopkins University of Medicine Sidney Kimmel Comprehensive Care Center

    Washington D.C., District of Columbia, 20016

Other trials in United States

About this study

Official title: A First-in-Human (FiH) Study of IK-595, an Oral Dual MEK/RAF Inhibitor, in Patients With RAS-or RAF-altered Advanced Solid Tumors

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.

Read the detailed description

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, a dual mitogen-activated protein kinase kinase (MEK)/ RAF kinase inhibitor, administered orally (PO) 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.

The study consists of an initial Dose Escalation phase using a Bayesian Optimal Interval (BOIN) design, followed by a Dose Expansion phase in 4 genetically/molecularly defined cohorts using 2-stage adaptive design.

During the Dose Escalation phase, backfilling may occur, where ≥ 3 additional patients can be enrolled at a given dose level once that dose level is deemed safe and tolerable by the Safety Review Committee. Backfilling includes, but is not limited to, patients with the following diagnoses: neuroblastoma RAS viral oncogene homolog-mutant (NRASmut) colorectal carcinoma (CRC), NRASmut malignant melanoma , Kirsten rat sarcoma viral oncogene homolog-mutant (KRASmut) CRC, KRASmut pancreatic cancer, KRASmut non-small cell lung cancer(NSCLC), B-Raf proto-oncogene, serine/threonine kinase-mutant (BRAFmut) Class II/III or BRAF fusion positive solid tumors, and Raf-1 proto-oncogene, serine/threonine kinase-mutant (CRAFmut) or fusion positive solid tumors.

Various dose levels and schedules will be explored.

Being tested
IK-595
Keywords
IK-595, RAS-MAPK Pathway, MEK Inhibitor, MEK/RAF Inhibitor
Medical subject headings
Colorectal Neoplasms, Pancreatic Neoplasms, Melanoma, Carcinoma, Non-Small-Cell Lung, Thyroid Neoplasms, Glioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IK-595Drug

    Oral tablet administered in 28-day or 30-day cycles until treatment discontinuation criteria are met.

Study groups in NCT06270082
Study groupRoleWhat they receive
IK-595ExperimentalDose Escalation and Dose Expansion
Receives: Drug: IK-595

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Treatment-emergent adverse events, including treatment-related adverse events, and serious adverse events

    • Frequency and severity of treatment-emergent adverse events, including treatment-related adverse events, and serious adverse events

    Measured: From treatment initiation through study completion, average of 36 months

  2. Dose Limiting Toxicities

    Number of patients with dose-limiting toxicities (Dose Escalation only)

    Measured: The first 30 days of treatment for each patient during Dose Escalation

  3. Treatment-Emergent Adverse Events

    Number and percentage of patients with ≥ 1 treatment-emergent adverse events leading to dose modifications and treatment discontinuation

    Measured: From treatment initiation through study completion, average of 36 months

  4. Recommended Phase 2 Dose (RP2D) and/or maximum tolerated dose (MTD) of IK-595

    Selection of dose level to take proceed with in Dose Expansion and/or Phase 2

    Measured: From treatment initiation through dose escalation, approximately 1 year

Secondary outcomes (10)

  1. Pharmacokinetics of IK-595: half-life (t1/2)

    half-life (t1/2)

    Measured: From treatment initiation through dose escalation, approximately 1 year

  2. Pharmacokinetics of IK-595: Area Under the Curve (AUC)

    AUC

    Measured: Approximately 1 year

  3. Pharmacokinetics of IK-595: Maximum Plasma Concentration (Cmax)

    Cmax

    Measured: Approximately 1 year

  4. Pharmacokinetics of IK-595: Minimum Plasma Concentration (Cmin)

    Cmin

    Measured: Approximately 1 year

  5. To evaluate pERK fold change from baseline in paired tumor biopsies

    To evaluate the pharmacodynamic effects of IK-595 on the levels of phosphorylated extracellular signal-regulated kinase (pERK) in paired tumor biopsies

    Measured: Through study completion, average of 36 months

  6. Antitumor activity per RECIST 1.1: Disease control rate (DCR) of IK-595 as a single agent

    Complete Response [CR] + Partial Response [PR] + stable disease ≥ 16 weeks

    Measured: Through study completion, average of 36 months

  7. Antitumor activity per RECIST 1.1: Time to response (TTR) of IK-595 as a single agent

    TTR

    Measured: Through study completion, average of 36 months

  8. Antitumor activity per RECIST 1.1: Duration of response (DOR) of IK-595 as a single agent

    DOR

    Measured: Through study completion, average of 36 months

  9. Antitumor activity per RECIST 1.1: Objective response rate (ORR) of IK-595 as a single agent

    ORR

    Measured: Through study completion, average of 36 months

  10. Antitumor activity: Median progression-free survival (PFS) of IK-595 as a single agent

    PFS

    Measured: Through study completion, average of 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Feb 2024
  2. Study start18 Dec 2023
  3. Primary completion8 Sep 2025
  4. Study completion8 Sep 2025

Why it stopped: Limited resources and strategic priorities

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Dose Escalation: BOIN design Dose Expansion: 4 genetically/molecularly defined cohorts using Simon 2-stage adaptive design
Masking
None (open label)
Enrolment
75 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06270082
Sponsor's protocol ID
IK595-001
Status last verified
Sep 2025
First submitted
31 Jan 2024
Last updated
19 Sep 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing IK-595 in people with Solid Tumor, Adult and Colorectal Cancer, run by Ikena Oncology at 15 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 35 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 19 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Limited resources and strategic priorities). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Treatment-emergent adverse events, including treatment-related adverse events, and serious adverse events (time frame: From treatment initiation through study completion, average of 36 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06270082.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2025.

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