Eligibility

Eligible Ages

Over 18 Years

Eligible Sex

All

Accepts Healthy Volunteers

No

Criteria

Eligibility Criteria

1. Ability to understand and the willingness to sign a written informed consent
document

2. Male or female ≥ 18 years of age

3. Confirmed diagnosis of clear cell RCC

4. Stage IV metastatic RCC per American Joint Committee on Cancer

5. Triplet Cohort (IO/IO): No prior systemic therapy for advanced RCC or prior adjuvant
therapy allowed.

6. Doublet Cohort: Participant must have progressed on at least one PD1 based doublet
regimen (IO/IO or IO/TKI). Prior adjuvant therapy is allowed and does count as one
line of systemic therapy.

7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 )

8. At least one measurable lesion as defined by RECIST 1.1

• A tumor lesion situated in a previously irradiated area is considered a
measurable/target lesion only if subsequent disease progression has been documented
in the lesion

9. Has pathology-confirmed RCC. Extra tissue should be submitted if available for
correlatives. Formalin-fixed paraffin-embedded tissue blocks are preferred to
slides. Details pertaining to tumor tissue submission can be found in the Lab
Procedures Manual.

10. Willing and able to undergo bone and brain scans at baseline and continue to have
scans performed if positive at screening.

11. Adequate organ function within 28 days prior to first dose of protocol-indicated
treatment, including:

- White blood cell (WBC) ≥ 2,000 /μL

- Absolute neutrophil count (ANC) ≥ 1,000/μL

- Platelet count ≥ 100,000/μL

- Hemoglobin (Hgb) ≥ 9.0 g/dL in prior 4 weeks. Blood transfusions are allowed to
achieve this.

- Serum creatinine ≤ upper limit of normal (ULN), or calculated creatinine
clearance ≥ 30 mL/min (per the Cockcroft-Gault formula,)

- Total bilirubin ≤ ULN (except subjects with Gilbert Syndrome, who must have
total bilirubin < 3.0 mg/dL)

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN

12. Women must not be breastfeeding while taking the study drug and for up to five
months after the last dose of study drug

13. Women of childbearing potential (WOCBP) must have a negative serum or urine
pregnancy test within 24 hours prior to receiving first dose of protocol-indicated
treatment

- "Women of childbearing potential" (WOCBP) is defined as any female who has
experienced menarche who has not undergone surgical sterilization (hysterectomy
or bilateral oophorectomy) or is not postmenopausal

- Menopause is defined clinically as 12 months of amenorrhea in a woman over 45
years of age in the absence of other biological or physiological causes

- If menopausal status is considered for the purpose of evaluating childbearing
potential, women < 62 years of age must have a documented serum follicle
stimulating hormone (FSH) level within laboratory reference range for
postmenopausal women, in order to be considered postmenopausal and not of
childbearing potential

14. Women of childbearing potential (WOCBP) must agree to follow instructions for
acceptable contraception prior to the study and from the time of signing consent,
for the duration of the study participation and for 23 weeks after their last dose
of protocol-indicated treatment

- The effects of HC-7366 on the developing human fetus are unknown. For this
reason and because first-in-class, first-in-human agents as well as other
therapeutic agents used in this trial are known to be teratogenic, women of
child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry
and for the duration of study participation. (Refer to Pregnancy Assessment
Policy MD Anderson Institutional Policy # CLN1114).

- Approved methods of birth control are as follows: Hormonal contraception (i.e.
birth control pills, injection, implant, transdermal patch, vaginal ring),
Intrauterine device (IUD), Tubal Ligation or hysterectomy, Subject/Partner post
vasectomy, Implantable or injectable contraceptives, and condoms plus
spermicide. Not engaging in sexual activity for the total duration of the study
and the drug washout period is an acceptable practice; however periodic
abstinence, the rhythm method, and the withdrawal method are not acceptable
methods of birth control. Should a woman become pregnant or suspect she is
pregnant while she or her partner is participating in this study, she should
inform her treating physician immediately.

15. Men not azoospermic who are sexually active with WOCBP must agree to follow
instructions for acceptable contraception prior to the study and from the time of
signing consent, for the duration of the study participation, and for 31 weeks after
their last dose of protocol-indicated treatment

16. Participant s with evidence of chronic hepatitis B virus (HBV) infection, the HBV
viral load must be undetectable on suppressive therapy, if indicated

17. Participant s with a history of hepatitis C virus (HCV) infection must have been
treated and cured. For participants with HCV infection who are currently on
treatment, they are eligible if they have an undetectable HCV viral load

18. Participant s with previously treated brain metastases may be eligible provided they
are radiologically (by MRI) and clinically stable (i.e., without evidence of disease
progression) for at least 4 weeks (28 days) by repeat imaging (repeat imaging should
be performed during study screening), with no evidence of new or enlarging brain
metastases, and without requirement for steroid treatment for at least 28 days prior
to the first dose of study drug or study therapy. (CT is acceptable if MRI is
contraindicated)

19. Participant s with a prior or concurrent malignancy whose natural history or
treatment does not interfere with the safety or efficacy assessment of the
investigational regimen are eligible for this study

20. Participant s with known history or current symptoms of cardiac disease, or history
of treatment with cardiotoxic agents, should have a clinical risk assessment of
cardiac function using the New York Heart Association Functional Classification. To
be eligible for this study, participant s should be class 2B or better

Exclusion Criteria

1. For the Triplet Cohort (Nivo/Ipi/HC-7366):

- Prior systemic treatment including neoadjuvant or adjuvant therapy including an
immune checkpoint inhibitor or TKI 2. For the Doublet Cohort (Nivo/HC-7366):

- More than 3 prior lines of systemic therapy allowed

- Has received any type of small molecule kinase inhibitor (including investigational
kinase inhibitor) ≤ 2 weeks before start of study drug or study therapy 3. ≤ 28 days
before first dose of protocol-indicated treatment:

- Major surgery requiring general anesthesia 4. ≤ 14 days before first dose of
protocol-indicated treatment:

- Radiosurgery or radiotherapy

- Minor surgery. (Note: Placement of a vascular access device is not considered minor
or major surgery)

- Active infection requiring systemic treatment 5. Known or suspected clinically
significant active bleeding including active hemoptysis 6. Inability to swallow oral
medication; or the presence of a poorly controlled gastrointestinal disorder that
could significantly affect the absorption of oral study drug - e.g. Crohn's disease,
ulcerative colitis, chronic diarrhea (defined as > 4 loose stools per day),
malabsorption, or bowel obstruction 7. Central nervous system (CNS) metastasis,
unless asymptomatic and radiologically (by MRI) and clinically stable (i.e., without
evidence of disease progression) for at least 4 weeks (28 days) by repeat imaging
(repeat imaging should be performed during study screening), with no evidence of new
or enlarging brain metastases, and without requirement for steroid treatment for at
least 28 days prior to the first dose of study drug or study therapy. (CT is
acceptable if MRI is contraindicated 8. Any condition requiring systemic treatment
with either corticosteroids (> 10 mg/day prednisone or equivalent daily) or other
immunosuppressive medications within 14 days prior to initiating protocol-indicated
treatment

- In the absence of active autoimmune disease: Subjects are permitted the use of
corticosteroids with minimal systemic absorption (e.g. topical, ocular,
intraarticular, intranasal, and inhalational) ≤ 10 mg/day prednisone or equivalent
daily; and physiologic replacement doses of systemic corticosteroids ≤ 10 mg/day
prednisone or equivalent daily (e.g. hormone replacement therapy needed in
participants with hypophysitis) 9. Active, known or suspected autoimmune disease

- Subjects with type I diabetes mellitus; hypothyroidism only requiring hormone
replacement; skin disorders such as vitiligo, psoriasis or alopecia not requiring
systemic treatment; or conditions not expected by the investigator to recur in the
absence of an external trigger are permitted to enroll 10. Known psychiatric
condition, social circumstance, or other medical condition reasonably judged by the
investigator to unacceptably increase the risk of study participation; or to
prohibit the understanding or rendering of informed consent or anticipated
compliance with and interpretation of scheduled visits, treatment schedule,
laboratory tests and other study requirements 11. Pregnant women are excluded from
this study because HC-7366 is novel, first-in-class small molecule agent with the
potential for teratogenic or abortifacient effects. Because there is an unknown but
potential risk for adverse events in nursing infants secondary to treatment of the
mother with HC-7366, breastfeeding should be discontinued if the mother is treated
with HC-7366. These potential risks may also apply to other agents used in this
study 12. Human immunodeficiency virus (HIV)-infected participants on effective
anti-retroviral therapy with undetectable viral load within 6 months are eligible
for this study 13. Participants who are receiving any other investigational agents