Study of BDC-3042 as Single Agent and in Combination With Pembrolizumab in Patients With Advanced Malignancies

Inclusion Criteria:

Able to understand and sign the informed consent form
Age 18 years or older at the time of informed consent
Has disease that is measurable by Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Subjects enrolled in Part 1 and Part 2 dose escalation cohorts must have:

a. Histologically/cytologically confirmed triple-negative breast cancer (TNBC), clear cell renal cell cancer (ccRCC), ovarian cancer, head and neck cancer, colorectal cancer, or non-small cell lung cancer (NSCLC) that is metastatic or unresectable with tumor progression after standard therapy who have no options for standard therapies which are known to confer clinical benefit. Subjects with ovarian cancer must have platinum resistant or platinum-refractory tumors.

Subjects enrolled in Part 3 and Part 4 dose expansion cohorts must have histologically/cytologically confirmed metastatic or unresectable TNBC or NSCLC with tumor progression after standard therapy who have no options for standard therapies which are known to confer clinical benefit.

Adequate organ function defined as follows:

Hematology: i. Absolute neutrophil count ≥ 1500 cells/mm3; ii. Platelet count ≥ 75,000 cells/mm3; iii. Hemoglobin ≥ 9 g/dL (and without transfusion within 7 days)
Renal: creatinine clearance ≥ 30 mL/min by Cockcroft-Gault estimate
Coagulation: Prothrombin time or international normalized ratio and activated partial thromboplastin time ≤ 1.5 × upper limit of normal (ULN) (unless receiving anticoagulation therapy)
Hepatic: i. Aspartate aminotransferase and alanine transaminase (ALT) ≤ 3 × ULN (or ≤ 5 × ULN in subjects with known hepatic metastases); ii. Total bilirubin ≤ 1.5 × ULN (isolated value > 1.5 × ULN is acceptable if direct bilirubin is < 35% of total)
Developed tumor progression after treatment with all standard therapies or have no appropriate available therapies
Expected life expectancy of > 12 weeks per the Investigator
Women of childbearing potential (WOCBP) should use a highly effective contraceptive measure (a method that can achieve a failure rate of less than 1% per year) during treatment and until 4 weeks after the end treatment.
Potent men that are partners of WOCBP must be willing to use condoms in combination with a second highly effective method of female contraception and agree not to donate sperm from screen through at least 4 months after last dose of study treatment. A male partner will be considered as potent unless surgically sterilized (with appropriate documentation of sterility).

Exclusion Criteria:

Active systemic yeast infection within 4 weeks before study treatment
Prior hospitalization for asthma during past year
Central nervous system metastases except for disease that is asymptomatic, clinically stable, and has not required steroids for at least 14 days before starting study treatment

Cardiac disease including:

Congestive heart failure New York Heart Association classes II-IV
QTcF prolongation > 450 milliseconds (ms) based on a 12-lead electrocardiogram (ECG) in triplicate or > 480 ms for subjects with bundle branch block
Serious or uncontrolled cardiac arrhythmia within 6 months before starting study treatment
Myocardial infarction, unstable angina pectoris, or coronary angioplasty, stenting, or surgery within 6 months before starting study treatment
Serious or uncontrolled hypertension (≥ 180 mmHg systolic or ≥ 120 mmHg diastolic) within 6 months before starting study treatment
Pericarditis or pericardial effusion that is symptomatic within 6 months before starting study treatment
Pulmonary disease including idiopathic pulmonary fibrosis, noninfectious interstitial lung disease, pneumonitis, chronic obstructive pulmonary disease (requiring daily treatment for dyspnea, oxygen therapy on an ongoing basis, or hospitalization within the past 6 months)
Hepatic disease resulting in symptomatic ascites, encephalopathy, coagulopathy, esophageal/gastric varices, or persistent jaundice
Arterial thrombotic event, stroke, or transient ischemia attack within 6 months before starting study treatment
Bleeding diathesis or uncontrolled bleeding within 7 days before starting study treatment
Bone marrow transplant or solid organ transplant

Infection including:

Disease requiring systemic therapy within 7 days before starting study treatment
Ongoing COVID-19 as determined by viral testing
Active human immunodeficiency virus (HIV) infection as determined at screening
Active hepatitis B infection as determined at screening
Active hepatitis C infection as determined at screening
Autoimmune disease requiring systemic disease-modifying or immunosuppressive therapy within 2 years before starting study treatment. Exceptions include disease managed with only replacement therapies (eg, thyroxine, etc.)
History of hemophagocytic lymphohistiocytosis/macrophage activation syndrome
Malignancy within 2 years before starting study treatment other than the disease under study. Exceptions include indolent or definitively treated disease not expected to require treatment during the study, affect the safety of subjects, or affect the endpoints of the trial
Any medical condition requiring corticosteroids (> 10 mg daily oral prednisone or equivalent) or other systemic immunosuppressive therapy within 28 days before starting study treatment. Exception: Intermittent or sporadic use of inhaled or topical steroids is allowed

Residual toxicity from previous treatment including:

Toxicity related to prior treatment not resolved to Grade 1
Neuropathy Grade > 2 Note: Exceptions to the above criteria include toxicities that do not pose a risk to vital organ systems (eg, alopecia) or toxicities that are stable as managed by replacement therapies (eg, hypothyroidism)
Subjects receiving immune checkpoint inhibitor: Toxicity Grade 3 related to prior immunotherapy and leading to treatment discontinuation
Any investigational agent within 28 days before starting study treatment or within 5 estimated elimination half-lives, whichever is shorter
Radiation therapy within 14 days before starting study treatment
History of severe hypersensitivity to any ingredient of BDC-3042 or study treatment (as applicable for combination study treatment)
Received live/attenuated virus vaccine within 28 days before starting study treatment
Major surgery within 28 days of starting study treatment (consult with Medical Monitor)
Actively enrolled in another clinical study, unless it is an observational (noninterventional) clinical study or the follow-up component of an interventional study
Patient is a lactating mother or pregnant as confirmed by pregnancy tests within 7 days prior to start of study treatment
Patient is unwilling or unable to follow protocol requirements
Ongoing bowel perforation or presence of bowel fistula or intra-abdominal abscess
Any condition that, in the opinion of the Investigator, would interfere with evaluation of BDC-3042 or interpretation of the patient's safety or study results