A PHASE 1/2, OPEN LABEL DOSE-ESCALATION AND EXPANSION TRIAL OF NKT2152, AN ORALLY ADMINISTERED HIF2 ALPHA INHIBITOR, TO INVESTIGATE SAFETY, PHARMACOKINETICS, PHARMACODYNAMICS AND CLINICAL ACTIVITY IN PATIENTS WITH ADVANCED CLEAR CELL RENAL CELL CARCINOMA
T
Theodore Logan, MD
Primary Investigator
Overview
This is a Phase 1/2 open label multicenter study of NKT2152. Phase 1 is a first in human (FIH) dose escalation study in patients aged 18 years or older with clear cell renal carcinoma (ccRCC) who have exhausted available standard therapy as determined by the investigator. Phase 1 is designed to determine the MTD and/or RP2D of NKT2152 as a single agent administered orally once daily. Depending on the tolerability and PK, additional dosing schedules may be tested. The RP2D will be based on the safety, tolerability, PK and preliminary anti-tumor activity and will not exceed the MTD. Phase 2 will make a formal evaluation of efficacy of NKT2152 in ccRCC patients.
Eligibility
You may be eligible for this study if you meet the following criteria:
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Conditions:
clear cell renal carcinoma,ccRCC
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Age: Between 18 Years - 100 Years
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Gender: All
Inclusion Criteria:
Diagnosis and Main Criteria for Inclusion: Patients must meet all of the following criteria to be
enrolled in this study.
1. Has the ability to understand and willingness to sign a written informed consent form before
the performance of any study procedures
2. Has locally advanced or metastatic ccRCC and has progressed during, are relapsed,
refractory and not amenable to curative therapy or standard therapy (Phase 1); has progressed
during treatment with at least 1 prior therapeutic regimen (Phase 2) that contains a PD-1 or
PD-L1 compound and/or a VEGF targeting agent, and a total of ≤ 4 prior therapeutic
regimens
3. Must have measurable disease per the Response Evaluation Criteria in Solid Tumors version
1.1 (RECIST 1.1)
4. Is of age ≥ 18 years
5. Has an Eastern Cooperative Oncology Group performance status of 0-2
6. Has a life expectancy of ≥ 3 months
7. Has adequate organ function defined as follows:
- Bone marrow: ANC ≥ 1.0× 109/L; hemoglobin level ≥ 10 g/dL without transfusion or erythropoietin support within 2 weeks prior to enrollment; platelet count ≥ 75,000/μL
- Hepatic: transaminase levels (AST/ALT) ≤ 2.5 × upper limit of normal (ULN) (≤ 5 × ULN if liver metastases present); total bilirubin (TBILI) ≤ 2.0 mg/dL in the absence of Gilbert’s disease
- Renal: Calculated creatinine clearance (CrCL) ≥ 30 mL/min (Cockcroft-Gault formula)
8. If a female patient of child-bearing potential, has a negative serum pregnancy test result
within 7 days before first study drug administration
9. If a female patient, must be surgically sterile, must be post-menopausal, or must agree to use
physician-approved method of birth control during screening, during the study, and for a
minimum of 28 days after the last study drug administration; or if a male patient with a
female partner, must agree to use physician-approved method of birth control during
screening, during the study, and for a minimum of 28 days after the last study drug
administration
Female patients of childbearing potential must meet all of the following criteria:
• Not pregnant (negative serum pregnancy test during Screening)
• Not breastfeeding
• Willing to use a protocol-recommended method of contraception or to abstain
from heterosexual intercourse from the start of treatment or until at least 28 days
after the last dose of treatment.
Note: A female patient is considered to be of childbearing potential unless she has
had a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy; has
medically documented ovarian failure (with serum estradiol and folliclestimulating hormone levels within the institutional laboratory postmenopausal range and a negative serum or urine beta human chorionic gonadotropin); or is
menopausal (age ≥55 years with amenorrhea for ≥6 months).
Male patients who can father a child must meet all of the following criteria:
• Willing to use a protocol-recommended method of contraception or to abstain
from heterosexual intercourse with females of childbearing potential from the
start of treatment until at least 28 days after the last dose of treatment, and
• Willing to refrain from sperm donation from the start of treatment until at least
90 days after the last dose of treatment.
Note: A male patient is considered able to father a child unless he has had a
bilateral vasectomy with documented aspermia or a bilateral orchiectomy
10. Able to swallow oral medications
Exclusion Criteria:
Main Criteria for Exclusion: Patients will be excluded from this study if they meet any of the
following criteria.
1. Known symptomatic brain metastases requiring >10 mg/day of prednisone (or its equivalent).
Patients with previously diagnosed brain metastases are eligible if they have completed their
treatment, have recovered from the acute effects of radiation therapy or surgery prior to the
start of NKT2152 treatment, fulfill the above steroid requirement for these metastases, and
are neurologically stable based on central nervous system imaging ≥4 weeks after CNSdirected treatment
2. Has a pulse oximetry reading less than 92% at screening, requires intermittent supplemental
oxygen, or requires chronic supplemental oxygen
3. History of another malignancy except for the following: adequately treated local basal cell or
squamous carcinoma of the skin, in situ cervical cancer, adequately treated papillary
noninvasive bladder cancer, other adequately treated Stage 1 or stage 2 cancers currently in
complete remission, or any other cancer that has been in complete remission for ≥ 2 years
4. Has failed to recover from the effects of prior anticancer therapy to baseline level or grade 1
severity (except for alopecia) per National Cancer Institute (NCI) Common Terminology
Criteria for Adverse Events (CTCAE); patients with treatable adverse effects such as
hypothyroidism or hypertension may be enrolled if the adverse effect is controlled with
treatment
5. Significant cardiovascular disease, including myocardial infarction, arterial
thromboembolism, or cerebrovascular thromboembolism, within 6 months prior to start of
NKT2152 treatment; symptomatic dysrhythmias or unstable dysrhythmias requiring medical
therapy; angina requiring therapy; symptomatic peripheral vascular disease; New York Heart
Association Class 3 or 4 congestive heart failure; ≥ Grade 3 hypertension (diastolic blood
pressure ≥100 mmHg or systolic blood pressure ≥160 mmHg); or history of congenital
prolonged QT syndrome or repeated demonstration of a QTc interval > 500 ms
6. Has received prior investigational therapy or standard therapy within 5 half-lives of the agent
or 4 weeks before the first administration of study drug, whichever is shorter
7. Has a bleeding diathesis or coagulopathy
8. DVT/pulmonary embolism are allowed as long as patient is not symptomatic and received 2
weeks or more of adequate anticoagulation
9. Has manifestations of malabsorption due to prior gastrointestinal (GI) surgery or GI disease
10. Has any other clinically significant cardiac, respiratory, or other medical or psychiatric
condition that might interfere with participation in the trial or interfere with the interpretation
of trial results
11. Has had major surgery within 4 weeks before first study drug administration; the following
procedures are not considered to be major surgeries: thoracentesis, paracentesis, port
placement, laparoscopy, thoracoscopy, bronchoscopy, endoscopic or ultrasonographic
procedures, mediastinoscopy, skin biopsy, incisional biopsy, image-guided biopsy for
diagnostic purposes, and routine dental procedures
12. Has known human immunodeficiency virus (HIV)
13. Has an active infection requiring systemic treatment
14. Is participating in another therapeutic clinical trial
15. Has received prior treatment with a HIF2 alpha inhibitor
Updated on
05 May 2024.
Study ID: 12922
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