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Brief Title: A Phase 1a/b Study of IK-175 as a Single Agent and in Combination With Nivolumab in Patients With Locally Advanced or Metastatic Solid Tumors and Urothelial Carcinoma

A Phase 1a/b, Open-Label, Dose-Escalation and Expansion Study of IK-175, an Oral Aryl Hydrocarbon Receptor (AHR) Inhibitor, as a Single Agent and in Combination With Nivolumab, a PD-1 Checkpoint Inhibitor in Patients With Locally Advanced or Metastatic Solid Tumors and Urothelial Carcinoma

INTRODUCTION

  • Org Study ID: IK175-001
  • Secondary ID: KYN-175
  • NTC ID: NCT04200963
  • Sponsor: Ikena Oncology

BRIEF SUMMARY

This study will be conducted in adult subjects diagnosed with any form of an advanced or metastatic solid tumors including urothelial carcinoma for which standard therapy is no longer effective or is intolerable. This is a phase 1, multi-center, open label study designed to assess safety and tolerability of IK-175 as a single agent and in combination with nivolumab, to determine the recommended phase 2 dose (RP2D). Disease response, pharmacokinetics (PK), pharmacodynamics, and response biomarkers will also be assessed.

  • Overall Status
    Recruiting
  • Start Date
    December 18, 2019
  • Phase
    Phase 1
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: To determine the Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD), and to characterize the dose-limiting toxicities (DLTs) of IK-175 as a single agent and in combination with nivolumab.

Primary Outcome 1 - Timeframe: Approximately 6 months

Primary Outcome 2 - Measure: Safety and tolerability of IK-175 as a single agent and in combination with nivolumab including acute and chronic toxicities, in determining a recommended phase 2 dose (RP2D) of IK- 175.

Primary Outcome 2 - Timeframe: Up to 100 days after the end of study treatment.

CONDITION

  • Urothelial Carcinoma
  • Urothelial Carcinoma Bladder
  • Bladder Cancer
  • Bladder Disease
  • Solid Tumor
  • Solid Carcinoma
  • Solid Tumor
  • Adult
  • Metastatic Cancer
  • Advanced Solid Tumor
  • Advanced Cancer
  • Metastatic Bladder Cancer
  • Metastatic Urothelial Carcinoma
  • Locally Advanced Solid Tumor
  • Neoplasms
  • Neoplasm Metastasis
  • Neoplasm Malignant
  • Neoplasm
  • Bladder
  • Urothelial Neoplasm
  • Neoplasm
  • Urinary Bladder
  • Bladder Neoplasm
  • Bladder Urothelial Carcinoma

ELIGIBILITY

Inclusion Criteria:
Adult patients ≥18 years of age.

- Patients with confirmed solid tumors (including urothelial carcinoma) who have locally recurrent or metastatic disease that has progressed on or following all standard of care therapies or who is not a candidate for standard treatment.

- For patients with urothelial carcinoma to be enrolled in the Combination Treatment arm, patients must have confirmation of urothelial carcinoma and have unresectable locally recurrent or metastatic disease that has progressed on or following all standard of care therapies, or who is not a candidate for standard treatment. Checkpoint inhibitor therapy with anti-PD-1 or anti-PD-L1 does not necessarily need to directly precede the study, but patients must have progressed on or within 3 months of receiving the last infusion/dose anti-PD-(L)1 therapy for inclusion in the Combination Treatment arm only.

- Have measurable disease.

- Accessible tumor that can be safely accessed for multiple core biopsies and patient is willing to provide tissue from newly obtain biopsies before and during treatment.

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

- Adequate organ function.

- Highly effective birth control.

- Time since the last dose of prior therapy to treat underlying malignancy (including other investigational therapy): 9a. Systemic cytotoxic chemotherapy: ≥ the duration of the most recent cycle of the previous regimen (with a minimum of 2 weeks for all, except 6 weeks for systemic nitrosourea or systemic mitomycin-C). 9b. Biologic therapy (eg, antibodies): ≥ 3 weeks or their dosing interval if shorter than 3 weeks (e.g. q2w therapy would require a 2-week washout). 9c. Small molecule therapies: ≥ 5 × half-life. 9d. Investigational Agent: ≥4 weeks or ≥5 × half-life, whichever is shorter
Exclusion Criteria:
Untreated symptomatic central nervous system (CNS) tumors or brain metastasis. Patients are eligible if CNS metastases are asymptomatic and do not require immediate treatment or have been treated and patients have neurologically returned to baseline (residual signs or symptoms related to the CNS treatment are permitted). In addition, patients must have been either off corticosteroids, or on a stable or decreasing dose of ≤10 mg daily prednisone (or equivalent) for at least 2 weeks prior to entering the Treatment period (Day 1).

- Patients who have not recovered to ≤ Grade 1 or baseline from all adverse events (AEs) due to previous therapies

- Has an active autoimmune disease that has required systemic treatment in past 2 years with the use of disease-modifying agents, corticosteroids, or immunosuppressive drugs; nonsteroidal anti-inflammatory drugs (NSAIDs) are permitted. Patients with type 1 diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.

- Any condition requiring continuous systemic treatment with either corticosteroids (>10mg daily prednisone equivalents) or other immunosuppressive medications within 2 weeks prior to first dose of study treatment (Inhaled or topical steroids and physiological replacement doses of up to 10 mg daily prednisone equivalent are permitted in the absence of active clinically significant [ie, severe] autoimmune disease.).

- Any other concurrent antineoplastic treatment or investigational agent except for allowed local radiation of lesions for palliation and hormone ablation.

- Uncontrolled or life-threatening symptomatic concomitant disease (including known symptomatic human immunodeficiency virus (HIV) positive with an AIDS defining opportunistic infection within the last year, or a current CD4 count <350 cells/uL, symptomatic active hepatitis B or C checked at screening, or active tuberculosis). Patients with HIV are eligible if: 6a. they have received antiretroviral therapy (ART) for at least 4 weeks prior to entering the Treatment period as clinical indicated while enrolled on study; 6b. they continue on ART as clinically indicated while enrolled on study; 6c. CD4 counts and viral load are monitored per standard of care by a local health care provider. - Patients that have undergone a major surgery within 3 weeks of starting trial treatment or has inadequate healing or recovery from complications of surgery prior to starting trial treatment. - Prior radiotherapy within 2 weeks of start of study treatment. Subjects must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had severe radiation pneumonitis. A 1-week washout is permitted for palliative radiation [≤ 2 weeks of radiotherapy] to non-CNS disease. - Prior AHR inhibitor treatment without Sponsor permission. - Potentially life-threatening second malignancy requiring systemic treatment within the last 3 years or which would impede evaluation of treatment response. Hormone ablation therapy is allowed within the last 3 years. Patients with history of prior early stage basal/squamous cell skin cancer or non-invasive or in situ cancers that have undergone definitive treatment at any time are eligible. - Recent or current significant cardiovascular disease (e.g. stroke, heart attack, heart failure, or arrhythmia). - Medical issue that limits oral ingestion or impairment of gastrointestinal function that is expected to significantly reduce the absorption of IK-175. - Clinically significant (ie, active) cardiovascular disease: cerebral vascular accident/stroke (<6 months prior to enrollment), myocardial infarction (<6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or the presence of any condition that can increase proarrhythmic risk (eg, hypokalemia, bradycardia, heart block) including any new, unstable, or serious cardiac arrhythmia requiring medication, or other baseline arrhythmia that might interfere with interpretation of ECGs on study (eg, bundle branch block). Patients with QTcF >450 msec for males and >470 msec for females on screening ECG are excluded. Any patients with a bundle branch block will be excluded with QTcF >450 msec. Males who are on stable doses of concomitant medication with known prolongation of QTcF (eg, Selective Serotonin Reuptake Inhibitor Antidepressants) will only be excluded for QTcF >470 msec.

- History of life-threatening toxicity related to prior immune therapy (eg. anti-CTLA-4 or anti-PD-1/PD-L1 treatment or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways) except those that are unlikely to re-occur with standard countermeasures (eg. hormone replacement after adrenal crisis).

- Has an active infection requiring systemic therapy.

- Treatment with any live/attenuated vaccine within 30 days of first study treatment.

- A woman of child-bearing potential (WOCBP) who has a positive pregnancy test or is breastfeeding prior to treatment.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Karim Malek, MD

Role: Study Director

Affiliation: Ikena Oncology

Overall Contact

Name: Karim Malek, MD

Phone: 6033618939, 8574196991

Email: mtimothy@ikenaoncology.com, jschroeder@ikenaoncology.com

LOCATION

Facility Status Contact
Facility: Rush University Medical Center
Chicago, Illinois 60612
United States
Status: Recruiting Contact: Contact
Alan Tan, MD
847-636-1543
alan_tan@rush.edu
Facility: START Midwest
Grand Rapids, Michigan 49546
United States
Status: Recruiting Contact: Contact
Nehal Lakhani
616-954-5554
yvette.cole@startmidwest.com
Facility: Memorial Sloan Kettering Cancer Center
New York, New York 10065
United States
Status: Recruiting Contact: Contact
David Aggen, MD
646-628-0118
aggend@mskcc.org
Facility: Sydney Kimmel Cancer Center Thomas Jefferson University
Philadelphia, Pennsylvania 19107
United States
Status: Recruiting Contact: Contact
Babar Bashir, MD
215-955-6000
mtimothy@ikenaoncology.com
Facility: UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania 15232
United States
Status: Recruiting Contact: Contact
Jason Luke, MD, FACP
412-647-2811
mientkiewiczk@upmc.edu
Facility: The Sarah Cannon Research Institute
Nashville, Tennessee 37203
United States
Status: Recruiting Contact: Contact
Meredith A McKean, MD
615-329-7274
Diana.CatalanNavarro@SarahCannon.com