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.
|Overal Status||Start Date||Phase||Study Type|
|Recruiting||December 18, 2019||Phase 1||Interventional|
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 - Time Frame: 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 - Time Frame: Up to 100 days after the end of study treatment.
1. Adult patients ≥18 years of age.
2. 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.
3. 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.
4. Have measurable disease.
5. 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.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
7. Adequate organ function.
8. Highly effective birth control.
9. 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
1. 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).
2. Patients who have not recovered to ≤ Grade 1 or baseline from all adverse events (AEs)
due to previous therapies
3. 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
4. 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
5. Any other concurrent antineoplastic treatment or investigational agent except for
allowed local radiation of lesions for palliation and hormone ablation.
6. 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.
7. 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.
8. 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.
9. Prior AHR inhibitor treatment without Sponsor permission.
10. 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.
11. Recent or current significant cardiovascular disease (e.g. stroke, heart attack, heart
failure, or arrhythmia).
12. Medical issue that limits oral ingestion or impairment of gastrointestinal function
that is expected to significantly reduce the absorption of IK-175.
13. 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.
14. 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).
15. Has an active infection requiring systemic therapy.
16. Treatment with any live/attenuated vaccine within 30 days of first study treatment.
17. A woman of child-bearing potential (WOCBP) who has a positive pregnancy test or is
breastfeeding prior to treatment.
Minimum Age: 18 Years
Maximum Age: N/A
Healthy Volunteers: No
Name: Jason Sager, MD
Role: Study Director
Affiliation: Ikena Oncology
Name: Marissa Timothy, MS
Grand Rapids, Michigan 49546
|Memorial Sloan Kettering Cancer Center
New York, New York 10065
David Aggen, MD
|Sydney Kimmel Cancer Center Thomas Jefferson University
Philadelphia, Pennsylvania 19107
Babar Bashir, MD
|UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania 15232
Jason Luke, MD, FACP
|The Sarah Cannon Research Institute
Nashville, Tennessee 37203
Meredith A McKean, MD