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

NCT06270082 | Terminated Phase 1 FDA Drug

• 1 other identifier: IK595-001
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 15

Brief 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 alterations in the RAS- MAPK pathway for whom there are no further treatment options known to confer clinical benefit.

Conditions

Solid Tumor, Adult; Colorectal Cancer; Pancreatic Cancer; Malignant Melanoma; Ras (Kras or Nras) Gene Mutation; BRAF Gene Mutation; CRAF Gene Mutation; Non-Small Cell Lung Carcinoma; Thyroid Carcinoma; Gliomas, Malignant

Keywords

IK-595; RAS-MAPK Pathway; MEK Inhibitor; MEK/RAF Inhibitor

Outcome Measures

Primary Outcomes (4)

• 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

  From treatment initiation through study completion, average of 36 months

• Dose Limiting Toxicities

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

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

• Treatment-Emergent Adverse Events

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

  From treatment initiation through study completion, average of 36 months

• 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

  From treatment initiation through dose escalation, approximately 1 year

Secondary Outcomes (10)

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

  From treatment initiation through dose escalation, approximately 1 year

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

  Approximately 1 year

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

  Approximately 1 year

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

  Approximately 1 year

• To evaluate pERK fold change from baseline in paired tumor biopsies

  Through study completion, average of 36 months

Other Outcomes (1)

• Antitumor activity: Median overall survival (OS) of IK-595 as a single agent

  Through study completion, average of 36 months

Study Arms (1)

IK-595

EXPERIMENTAL

Dose Escalation and Dose Expansion

Drug: IK-595

Interventions

IK-595 DRUG

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

IK-595

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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;
• 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).

Sponsors & Collaborators

• Ikena Oncology: lead

Study Sites (15)

City of Hope

Duarte, California, 91010, United States

Location

University of California Irvine

Orange, California, 92868, United States

Location

Sarah Cannon Research Institute at HealthOne

Denver, Colorado, 80218, United States

Location

Johns Hopkins University of Medicine Sidney Kimmel Comprehensive Care Center

Washington D.C., District of Columbia, 20016, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

START Midwest

Grand Rapids, Michigan, 49546, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

University of Pittsburgh Medical Center- Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Next Oncology

Austin, Texas, 78758, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Next Oncology- San Antonio

San Antonio, Texas, 78229, United States

Location

INOVA Schar Cancer Institute

Fairfax, Virginia, 22031, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Pancreatic Neoplasms; Melanoma; Carcinoma, Non-Small-Cell Lung; Thyroid Neoplasms; Glioma

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Head and Neck Neoplasms; Thyroid Diseases; Neoplasms, Neuroepithelial; Neoplasms, Glandular and Epithelial

Study Officials

• Caroline Germa, MD

  Ikena Oncology

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose Escalation: BOIN design Dose Expansion: 4 genetically/molecularly defined cohorts using Simon 2-stage adaptive design

Study Record Dates

• First Submitted: January 31, 2024
• First Posted: February 21, 2024
• Study Start: December 18, 2023
• Primary Completion: September 8, 2025
• Study Completion: September 8, 2025
• Last Updated: September 19, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (15)