Brief Title: HC-7366 to Establish the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D)

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Determination of MTD of HC-7366

Primary Outcome 1 - Timeframe: Within 18 months of last patient enrolled

Primary Outcome 2 - Measure: Determination of Recommended Phase 2 dose of HC-7366

Primary Outcome 2 - Timeframe: Within 18 months of last patient enrolled

Primary Outcome 3 - Measure: Occurrence of dose-limiting toxicities (DLTs)

Primary Outcome 3 - Timeframe: Within 18 months of last patient enrolled

Primary Outcome 4 - Measure: Incidence and severity of treatment-emergent adverse events (TEAEs) and treatment related TEAEs according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v 5.0

Primary Outcome 4 - Timeframe: Within 18 months of last patient enrolled

Primary Outcome 5 - Measure: Incidence of TEAEs leading to premature discontinuation

Primary Outcome 5 - Timeframe: Within 18 months of last patient enrolled

Primary Outcome 6 - Measure: Incidence of laboratory abnormalities

Primary Outcome 6 - Timeframe: Within 18 months of last patient enrolled

Primary Outcome 7 - Measure: based on NCI CTCAE grades of hematology

Primary Outcome 7 - Timeframe: Within 18 months of last patient enrolled

Primary Outcome 8 - Measure: serum chemistry

Primary Outcome 8 - Timeframe: Within 18 months of last patient enrolled

Primary Outcome 9 - Measure: and urinalysis test results

Primary Outcome 9 - Timeframe: N/A

Primary Outcome 10 - Measure: Incidence of abnormalities observed in 12 lead ECG parameters

Primary Outcome 10 - Timeframe: N/A

Primary Outcome 11 - Measure: Incidence of abnormalities observed in vital signs measurements

Primary Outcome 11 - Timeframe: N/A

CONDITION

• Squamous Cell Carcinoma of Head and Neck
• Colo-rectal Cancer
• Non Small Cell Lung Cancer
• Transitional Cell Carcinoma of the Bladder
• Other Solid Tumors
• Clear Cell Renal Cell Carcinoma

ELIGIBILITY

Inclusion Criteria:
1. Have a signed an informed consent form prior to any study specific procedures or treatment

- 2. Be ≥18 years of age (male or female) at the time of consent

- 3. Phase 1a:
Have 1 of the following tumor types with qualifying characteristics, and have received at least 1 and no more than 5 prior lines of therapy for metastatic (stage IV) disease:

- 1. SCCHN

- 2. CRC

- 3. NSCLC

- 4. TCC

- 5. Other solid tumors (eg, carcinoma of unknown primary) with the exception of rapidly progressing neoplasms (eg, pancreatic cancer, glioblastoma, hepatocellular carcinoma). Note: Subjects do not need to have progressed through all possible available therapies with known clinical benefit for their respective cancers to participate in this study. Note: Subjects with SCCHN, CRC, NSCLC, and TCC are a priority and should constitute as a whole, at least 50% of the enrolled population. Enrollment of all others will be capped when reaching a combined 50%, in order to maintain 18 slots for subjects with SCCHN, CRC, NSCLC, and TCC.
Phase 1b:
Have renal cell carcinoma with respective qualifying characteristics:

- 1. Histological or cytological proof of component (any percentage) of clear cell RCC, excluding subjects that have any component of collecting duct or medullary histology are eligible

- 2. Subjects with residual, but well-controlled endocrinopathy (eg, hypothyroidism) are eligible

- 3. Subjects with metastatic or locally advanced unresectable RCC Note: Prior nephrectomy is not mandatory.

- 4. Subjects with progressive disease after receipt of at least 2 and no more than 5 prior lines of therapy for metastatic (stage IV) disease, including but not limited to VEGF-directed tyrosine kinase inhibitors (TKIs), high-dose IL-2 , immune checkpoint inhibitors, mTOR inhibitors, or belzutifan, alone or in combination. Note: A line of therapy is considered complete once the patient has progressed following such treatment. If a treatment regimen is changed before disease progression due to toxicity, for example, this is still considered part of the same line of therapy. In addition, maintenance therapy [that is, therapy with a different drug or drugs given to conserve an existing response or stable disease before disease progression] is not considered an additional line of therapy.

- 4. Have at least 1 radiologically measurable lesion as per Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 defined as a lesion that is at least 10 mm in longest diameter or lymph node that is at least 15 mm in short axis imaged by CT scan or magnetic resonance imaging and obtained by imaging within 28 days prior to study treatment. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions

- 5. Have resolution of all previous treatment related toxicities to Grade 1 severity or lower, except for stable sensory neuropathy (≤Grade 2) and alopecia. If the subject received major surgery or radiation therapy of >30 Gy, they must have recovered from the toxicity and/or complications from the intervention

- 6. If subjects were previously treated with immune checkpoint inhibitors, at least 4 weeks must have elapsed since the last dose, and they must have recovered from toxicities as mentioned in above Criterion #5

- 7. Subjects must have at least one biopsiable lesion at baseline. Biopsies in this clinical study will conform to American Society of Clinical Oncology's Ethical Framework for Including Research Biopsies in Oncology Clinical Trials. Provided there are suitable and accessible lesions, no biopsy contraindications, minimal risk of complications and a positive informed decision, subjects are willing to provide fresh tissue for biomarker analysis, and, based on the adequacy of the tissue sample quality, for assessment of biomarker status. Two biopsies will be necessary: at baseline (within 15 days prior to study Day 1) and at the time of the first response assessment CT scan at Cycle 3/Day 1 (+7 days). Newly obtained biopsy specimens are preferred to archived samples and formalin fixed, paraffin embedded block specimens are preferred to slides. Biopsies should not be taken from target lesions

- 8. Have Eastern Cooperative Oncology Group performance status of 0 or 1 and sustained between screening and initiation of dosing on Day 1

- 9. Have no swallowing difficulties that would prevent compliance with oral dosing

- 10. Have not experienced >10% body weight loss in the previous 4 weeks

- 11. Have a serum albumin level >3 g/dL

- 12. Have life expectancy of 3 months or greater as determined by the treating physician

- 13. Have adequate organ function on Day 1, as defined by meeting all of the following criteria:
1. Total bilirubin ≤1.5 × upper limit of normal (ULN) OR direct bilirubin ≤ULN for subjects with total bilirubin levels >1.5 x ULN

- 2. Aspartate aminotransferase and alanine aminotransferase ≤2.5 × ULN or ≤5 × ULN for subjects with known hepatic metastases

- 14. Have adequate renal function on Day 1, as defined by creatinine ≤1.5 × ULN and creatinine clearance ≥60 mL/min, as per the below Cockcroft Gault formula

- 15. Have adequate hematologic function on Day 1, as defined by meeting all of the following criteria:
1. Hemoglobin ≥9 g/dL (uncorrected by red blood cell transfusion or erythropoietin support)

- 2. Absolute neutrophil count ≥1.5 × 109/L

- 3. Platelet count ≥100 × 109/L

- 16. Have adequate coagulation function on Day 1, as defined by either of the following criteria:
1. International normalized ratio (INR) <1.5 × ULN OR for subjects receiving warfarin or low molecular weight heparin, the subject must, in the investigator's opinion, be clinically stable with no evidence of active bleeding while receiving anticoagulant therapy. The INR for these subjects may exceed 1.5 × ULN if that is the goal of anticoagulant therapy - 2. Activated partial thromboplastin time <1.5 × ULN unless subject is receiving anticoagulant therapy, provided prothrombin time or partial thromboplastin time is within therapeutic range of intended use of anticoagulants - 17. Have normal or adequately controlled pan-endocrine function (pituitary, adrenal, thyroid, pancreatic, gonadal). Subjects on hormonal supplementation must be stable at their treatment doses - 18. Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required - 19. Female subjects of childbearing potential must be willing to use an adequate form of contraception from the signing of the ICF until 90 days after the last dose of study medication - 20. Female subjects must agree not to breastfeed and not to donate ova starting at screening and throughout the study treatment, and for 90 days after the final administration of study drug - 21. Male subjects with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy or for the time their partner is breastfeeding throughout the study treatment and for 90 days after the final administration of study drug - 22. Male subjects must not donate sperm during the treatment period and for at least 90 days after the final administration of the study drug - 23. Male subjects with female partner(s) of child bearing potential must agree to use a condom with spermicide during the treatment period and for at least 90 days after the final administration of the study drug - 24. Be willing and have the ability to comply with scheduled visits (including geographical proximity), treatment plans, laboratory tests, and other study procedures.
Exclusion Criteria:
1. Had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to the first dose of study treatment or who has not recovered from adverse reactions due to a previously administered agent or major surgery

- 2. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment

- 3. Has a diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment. The use of physiologic doses of corticosteroids may be approved after consultation with the sponsor

- 4. Has known history of active tuberculosis

- 5. Has known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)

- 6. Has known active hepatitis B (eg, hepatitis B surface antigen reactive) or hepatitis C (eg, hepatitis C virus ribonucleic acid [RNA] [qualitative]) infection

- 7. Has been diagnosed with any infectious process that would, in the opinion of the investigator, interfere with study participation, especially regarding site-specific testing and isolation requirements. This applies to viral infections including, but not limited to, severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection

- 8. Has a history of clinically severe autoimmune disease, or history of organ transplant

- 9. Has a history of retinitis or photosensitive skin disorders including (but not limited to) erythema multiforme, atopic eczema, psoriasis, viral exanthemata, pemphigus, and dermatitis herpetiformis

- 10. Has known additional malignancy that is progressing or required active treatment within the previous 5 years. Exceptions include basal cell carcinoma or squamous cell carcinoma of the skin that has undergone potentially curative therapy, superficial bladder cancer, or in situ cervical cancer. Subjects with other malignancies are eligible if they were cured by surgery alone or surgery plus radiotherapy and have been continuously disease free for at least 5 years

- 11. Has known active central nervous system metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of disease progression by imaging for at least 4 weeks prior to the first dose of study treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using systemic steroids for at least 7 days prior to study treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability

- 12. Has a history of interstitial lung disease, pneumonitis within 12 months prior to screening, or current pneumonitis

- 13. Has an active infection requiring systemic therapy

- 14. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator

- 15. Has a clinically significant cardiovascular disease such as unstable angina, myocardial infarction, or acute coronary syndrome, symptomatic or uncontrolled arrhythmia, congestive heart failure, baseline electrocardiogram (ECG) abnormalities, including, but not limited to, QTc prolongation (as calculated using Fridericia formula) to greater than 450 ms for males or to greater than 470 ms for females, or any Class III or IV cardiac disease as defined by the New York Heart Association Functional Classification

- 16. Has overt or latent disorders of the exocrine pancreas (such as acute or chronic pancreatitis of any etiology) or chronic (including autoimmune) gastrointestinal disorders such as Crohn's disease, ulcerative colitis, rheumatoid arthritis, lupus, scleroderma, Sjogren's syndrome, and polyarteritis nodosa

- 17. Has a known psychiatric or substance abuse disorder(s) that would interfere with informed consent or cooperation with the requirements of the study

- 18. Is pregnant or breastfeeding or expecting to conceive children within the projected duration of the study, starting with the screening visit through 90 days after the final administration of the study drug

- 19. Is a first degree relative of the investigator, staff, or study sponsor.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Jose Iglesias, MD

Role: Study Director

Affiliation: Consultant Chief Medical Officer for HiberCell, Inc.

Overall Contact

Name: N/A

Phone: N/A

Email: N/A

LOCATION