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