This trial is measuring the safety and maximum tolerated dose of a new experimental cancer drug (BNA035) in people with advanced solid cancersA Phase 1 Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of BNA035 in Patients With Advanced Solid Tumors

Inclusion

Patients must meet all of the following criteria to be eligible for enrollment in this study:

1. Male or female ≥ 18 years of age.
2. Histologically or cytologically confirmed advanced malignant solid tumor that is refractory to or intolerant of all standard therapy or for which no standard therapy is available.
3. Measurable disease as per RECIST 1.1, or per Response Assessment in Neuro-Oncology (RANO) criteria for patients with glioblastoma multiforme and documented by computed tomography (CT) and/or magnetic resonance imaging (MRI).
4. All persisting toxic effects of any prior anti-tumor therapy resolved to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 Grade ≤ 1 or baseline before the first dose of study drug (with the exception of alopecia [Grade 1 or 2 permitted] and neurotoxicity [Grade 1 or 2 permitted]).
5. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.
6. Life expectancy of ≥ 3 months, in the opinion of the Investigator.

7. Adequate organ function defined as follows:

   1. Hematologic: Platelets ≥ 100 x 109/L; Hemoglobin ≥ 9.0 g/dL; Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (without blood transfusion, platelet transfusion, or growth factors within previous 7 days of the hematologic laboratory values obtained at Screening visit).
   2. Hepatic: Aspartate aminotransferase (AST)/ Alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN) (if liver metastases are present, ≤ 5 x ULN); Total or conjugated bilirubin ≤ 1.5 x ULN.
   3. Renal: Creatinine clearance (CLcr) ≥ 45 mL/min as calculated by the Cockcroft Gault method.
8. Coagulation: Patients on full-dose oral anticoagulation, except warfarin, which is an excluded medication, must be on a stable dose (minimum duration 14 days). Patients on low molecular weight heparin will be allowed.
9. Negative serum pregnancy test for female patients.

10. If of childbearing potential, female patients must be willing to use highly effective double contraceptive measures starting with the Screening visit through 90 days after the last dose of study treatment.

    Double contraception is defined as a condom AND one other form of the following:

    • Established hormonal contraception (with approved oral contraceptive pills, long-acting implantable hormones, injectable hormones);
    • A vaginal ring or an intrauterine device (IUD);
    • Documented evidence of surgical sterilization at least 6 months prior to Screening (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, or bilateral oophorectomy for women or vasectomy for men [with appropriate post-vasectomy documentation of the absence of sperm in semen] provided the male partner is a sole partner).

    Women not of childbearing potential must be post-menopausal for ≥ 12 months. Post-menopausal status will be confirmed through testing of follicle-stimulating hormone (FSH) levels ≥ 40 IU/L at Screening for amenorrhoeic female participants. Females who are abstinent from heterosexual intercourse will also be eligible.

    Periodic abstinence (e.g., calendar, ovulation, symptothermal, post ovulation methods) and withdrawal are not considered highly effective methods of birth control. Complete abstinence for the duration of the study through 90 days after the last dose of study treatment is acceptable if this is the established and preferred contraception for the patient.

    Female patients who are in same-sex relationships are not required to use contraception.

11. Male patients with a female partner(s) of childbearing potential must agree to use highly effective contraceptive measures throughout the trial starting with the Screening visit through 90 days after the last dose of study treatment is received. Males with pregnant partners must agree to use a condom; no additional method of contraception is required for the pregnant partner.

    Acceptable methods of contraception include:

    • Vasectomy (> 30 days since vasectomy with no viable sperm);
    • Surgical sterility in female partner(s) (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy);
    • Double contraception, condom AND the use of an effective contraceptive for the female partner that includes: oral contraceptive pills, long-acting implantable hormones, injectable hormones, a vaginal ring or an IUD.

    Patients with same-sex partners (abstinence from penile-vaginal intercourse) are eligible when this is their preferred and usual lifestyle.

    Note: Abstinence is acceptable if this is the established and preferred contraception method for the patient.

12. Males must not donate sperm for at least 90 days after the last dose of study drug.
13. Able and willing to provide written informed consent to participate in the study.
14. Patients with history of human immunodeficiency virus (HIV) infection should have a cluster of differentiation 4+ (CD4+) T cell count ≥ 350 cells/µL at Screening.
15. Patients with serological evidence of chronic hepatitis B virus infection (HBV) should have HBV viral load below the limit of quantification at Screening.
16. Patients with serological evidence of hepatitis C virus infection (HCV) should have completed curative antiviral treatment and have HCV viral load below the limit of quantification at Screening.
17. Patients must not be using immunosuppressive medication > 10 mg prednisolone per day or equivalent, or 2 mg dexamethasone for glioblastoma multiforme (GBM) patients, within 14 days prior to the first dose of the study drug. Note: Use of immunosuppressive medications as prophylaxis in patients with contrast allergies are acceptable. In addition, temporary uses of corticosteroids considered non-clinically significant may be approved on a case-by-case basis in discussion with the Sponsor.