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. Eligible patients will have received \<=4 prior lines lines of therapy.
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.
Phase 2 will evaluate the safety, pharmacokinetics and antitumor efficacy of NKT2152 in ccRCC patients.
Inclusion Criteria:
* Has the ability to understand and willingness to sign a written informed consent form before the performance of any study procedures
* Has locally advanced or metastatic ccRCC and has progressed during treatment, 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.
* Must have measurable disease per the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
* Is of age ≥ 18 years
* Has an Eastern Cooperative Oncology Group performance status of 0-2
* Has a life expectancy of ≥ 3 months
* Has adequate organ function
Exclusion Criteria:
* 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 CNS-directed treatment.
* Has a pulse oximetry reading less than 92% at screening, requires intermittent supplemental oxygen, or requires chronic supplemental oxygen.
* 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
* 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
* 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
* Has received prior treatment with a HIF2α inhibitor
