A Multicenter, Open-label, Phase 1/1b Dose Finding, Safety, and Pharmacokinetic Study of MBRC-101, an Anti-EphA5 Monomethyl Auristatin E (MMAE) Antibody Drug Conjugate, in Advanced Refractory Solid Tumors.

Inclusion Criteria

1. Provide written consent on an Informed Consent Form (ICF), approved by an

Institutional Review Board (IRB)/Independent Ethics Committee (IEC), prior to any

study-specific evaluation. Patients should have the ability to read and understand

the ICF, ask for any clarifications from the study staff, and be able to comply with

all planned study procedures.

2. 18 years of age or older at the time of informed consent.

3. Female patients must be at least 2 years postmenopausal (defined as 2 years without

menses), surgically sterile (at least 6 months prior to dosing; must be documented)

or practicing effective contraception (must agree to use 2 forms of contraception, 1

of which must be a barrier method) and willing to continue to use effective

contraception for the duration of study participation and for 6 months after the

final dose of study drug. Female patients must be nonlactating and have a negative

serum pregnancy test result at screening and baseline.

4. Male patients must agree to use effective contraception (must agree to use 2 forms

of contraception, 1 of which must be a barrier method) for the duration of study

participation and for 6 months after the final dose of study drug.

5. Have a histologic or cytologic diagnosis of malignant solid tumor for which there

are no standard of care treatment options known to confer a clinical benefit or for

which the patient is ineligible or declines.

A. For Phase 1 dose escalation: histologic or cytologic diagnosis of malignant solid

tumor of any type. The Sponsor may remove specific tumor indications based on

emerging, real-time study data.

B. For Phase 1b dose expansion:

i. Cohort A: Histologic or cytologic diagnosis of NSLC (adenocarcinoma and SCC).

ii. Cohort B: Histologic or cytologic diagnosis of TNBC or HR positive, HER2

negative breast cancer.

iii. Cohort C: Histologic or cytologic diagnosis of the following advanced

metastatic solid tumors refractory to standard treatment: pancreatic adenocarcinoma,

gastric adenocarcinoma, hepatocellular carcinoma, ovarian adenocarcinoma, and

squamous cell carcinoma including, but not limited to, primary malignancies of the

head and neck, esophagus, cervix, and skin. The Sponsor may add or remove specific

tumor indications based on emerging, real-time study results.

6. For Phase 1 and Phase 1b, availability of a tumor tissue sample (formalin-fixed

paraffin embedded [FFPE]) must be confirmed for analysis of EphA5 expression based

on IHC. Tumor biopsies are not required and should not be performed to assess

eligibility.

A. For Dose Escalation (Phase 1) and Dose Expansion (Phase 1b), tumor EphA5

expression will not be required for enrollment.

7. For Dose Escalation (Phase 1), patients may have evaluable disease or measurable

disease according to RECIST v1.1). For Dose Expansion (Phase 1b), patients must have

measurable disease according to RECIST v1.1.

8. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.

9. Life expectancy ≥ 3 months as assessed by the investigator.

10. Hematologic function, as follows (no red blood cell [RBC] or platelet transfusions

are allowed within 14 days of the first dose of MBRC-101):

A. Absolute neutrophil count (ANC) ≥ 1.0 × 109/L B. Platelet count ≥ 100 × 109/L C.

Hemoglobin ≥ 9 g/dL

11. eGFR ≥ 30 mL/min by the CKD-EPI or similar equation or as measured by 24 hour urine

collection.

12. Total bilirubin ≤ 1.5 × upper limit normal (ULN).

13. AST ≤ 3.0 × ULN.

14. ALT ≤ 3.0 × ULN.

15. International normalised ratio (INR) < 1.5 (or ≤ 3.0 if on therapeutic

anticoagulation).

16. Treatment with other agents for cancer, if received, must have been discontinued ≥ 2

weeks prior to first dose of study drug.

Prior ADC therapy is allowed. Prior agents conjugated to MMAE are allowed for Phase 1 but

not Phase 1b.

Exclusion Criteria

1. Preexisting sensory neuropathy Grade ≥ 2.

2. Preexisting motor neuropathy Grade ≥ 2.

3. Uncontrolled central nervous system metastases

4. Use of any investigational drug within 14 days prior to the first dose of study

drug.

5. Any anticancer therapy within 14 days prior to the first dose of study drug,

including: small molecules, immunotherapy, chemotherapy, monoclonal antibody

therapy, radiotherapy, or any other agents to treat cancer (anti-hormonal therapy

given for advanced prostate cancer or as adjuvant therapy for early stage, hormone

receptor (HR) positive breast cancer is not considered cancer therapy for the

purpose of this protocol).

6. Patients with immunotherapy related AEs requiring high doses of steroids (≥ 40

mg/day of prednisone) are not eligible.

7. Strong CYP3A or inducers within 14 days prior to the first dose of study drug.

8. Thromboembolic events and/or bleeding disorders ≤ 14 days (e.g., venous

thromboembolism [VTE] or pulmonary embolism [or PE]) prior to the first dose of

study drug.

9. Documented history of a cerebral vascular event (stroke or transient ischemic

attack), unstable angina, myocardial infarction, or cardiac symptoms (including

congestive heart failure) consistent with New York Heart Association Class 3-4

within 6 months prior to the first dose of MBRC-101.

10. A baseline QT (time from the beginning of the Q wave to the end of the T wave)

interval as corrected by Fridericia's formula (QTcF) > 470 msec.

11. Human immunodeficiency virus (HIV) infection with 1 or more of the following:

A. Acquired immunodeficiency syndrome (AIDs)-defining opportunistic infection within

6 months of the start of screening; B. A change in antiretroviral therapy within 3

months of the start of screening and viral load > 500 copies/mL; C. Receiving

antiretroviral therapy that may interfere with study drug; D. CD4 count < 350 at

screening.

12. Active or symptomatic viral hepatitis. Patients who have been properly treated for

hepatitis C infection can be included if they do not have active hepatitis C.

13. Known sensitivity to any of the ingredients of the investigational product MBRC-101.

14. Major surgery within 28 days prior to first dose of study drug.

15. History of another malignancy within 3 years before the first dose of study drug, or

any evidence of residual disease from a previously diagnosed malignancy. Allowed

exceptions are patients with:

A. Non-melanoma skin cancer considered completely cured; B. Localized prostate

cancer treated with curative intent with no evidence of progression; C. Low-risk or

very low-risk (per standard clinical guidelines) localized prostate cancer under

active surveillance without immediate intent to treat; D. Malignancy that is

otherwise considered cured with minimal risk of recurrence.

16. Currently receiving systemic antimicrobial treatment for active infection

(bacterial, viral, or fungal) at the time of first dose of MBRC-101. Routine

antimicrobial prophylaxis is permitted.

17. For Phase 1b dose expansion, prior ADC therapy is not allowed if the agent is

conjugated to MMAE. Prior agents conjugated to MMAE are allowed for Phase 1.

18. Condition or situation which, in the investigator's opinion, may put the patient at

significant risk, may confound the study results, or may interfere significantly

with patient's participation in the study.

19. Any medical, psychiatric, addictive, or other kind of disorder which compromises the

ability of the patient to give written informed consent and/or to comply with

procedures.

20. Active ocular surface disease at baseline or any components of the ophthalmologic

history which, in the investigator's opinion, may place the patient at significant

risk.