Study of LVGN3616 and LVGN6051±LVGN7409 in Combination With Nab-Paclitaxel or Bevacizumab and Cyclophosphamide in Metastatic Solid Tumors

Exclusion Criteria

• •Any treatment specifically for systemic tumor control given within 3 weeks before the initiation of therapy; within 2 weeks if cytotoxic agents were given weekly, within 6 weeks for nitrosoureas or mitomycin C; within 5 half-lives for targeted agents with half-lives and pharmacodynamic effects lasting \< 5 days; or failure to recover from toxic effects of any previous therapy. A drug that has not received regulatory approval for any indication within 14 or 21 days of treatment for a non-myelosuppressive or myelosuppressive agent, respectively: patients must recover for previous cancer therapy, and are ready to proceed with further cancer therapy.
• •Uncontrolled intercurrent illness including but not limited to:
• •* ongoing or active infection requiring intravenous antibiotics
• •* symptomatic congestive heart failure (New York Heart Association Class III or IV)
• •* history of myocardial infarction, unstable angina, stroke or transient ischemic attack within 6 months before study enrollment
• •* lesions invading or encasing any major blood vessels and cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation. Uncontrolled hypertension defined as sustained blood pressure (BP) \> 140 mm Hg systolic or \> 90 mm Hg diastolic despite optimal antihypertensive treatment (apply to bevacizumab-based regimens only)
• •* history or current evidence of uncontrolled ventricular arrhythmia
• •* congenital long QT syndrome, or any known history of torsade de pointes, or family history of unexplained sudden death
• •* clinically significant bleeding or active gastric or duodenal ulcer
• •* chronic diarrhea diseases considered to be clinically significant by investigator
• •* Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose of study treatment, or any gastrointestinal disorders associated with a high risk of perforation or fistula formation
• •* other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation, or may interfere with the interpretation of study results, and in the judgment of the Investigator would make the patient inappropriate for entry into this study Note: Subjects with a diagnosis of incidental, subsegmental pulmonary embolism or deep vein thrombosis are allowed if stable, asymptomatic, and treated with a stable dose of permitted anticoagulation for at least 1 week before first dose of study treatment.
• •Unresolved clinically significant Grade 1 or higher toxicity from prior therapy.
• •History of allergic reactions to the study drugs, or any component of the products.
• •Presence of other active invasive cancers that requires active treatment other than hormonal therapy.
• •Currently receiving an investigational drug in a clinical trial or participating in any other type of medical research judged not to be scientifically or medically compatible with this study. If a patient is currently enrolled in a clinical trial involving non-approved use of a therapeutic device for cancer control, then agreement with the investigator and the sponsor (MD Anderson IND Office) is required to establish eligibility.
• •Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: Bacille Calmette-Guérin vaccine, measles, mumps, rabies, rubella, typhoid vaccine, varicella/zoster, and yellow fever. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines are live attenuated vaccines and are not allowed. COVID19 vaccines including killed virus are allowed.
• •Caution should be exercised when administering nab-paclitaxel concomitantly with known substrates or inhibitors of CYP2C8 and CYP3A4 (https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers).
• •Symptomatic primary tumors or metastasis in the brain and/or central nervous system that are uncontrolled with antiepileptics and/or require steroids at a dose of prednisone \> 10 mg/day or equivalent.
• •Evidence of leptomeningeal or lymphangitic carcinomatosis.
• •A history of another primary malignancy that is currently clinically significant, requiring active intervention except for hormone therapy.
• •Lactation or pregnancy.
• •Human immunodeficiency virus requiring HAART treatment due to unknown drug-drug interactions or has known active hepatitis B (e.g., HBsAg reactive) or C virus (e.g., HCV RNA \[quantitative\] is detected) infection: patients who have had active HBV or HCV infections in the past but have evidence of viral clearance as shown by negative viral load, i.e., undetectable HBV DNA or HCV RNA, will be eligible.
• •Concurrent immunosuppressive therapy or steroid (\> 10 mg/day prednisone or equivalent).
• •History of autoimmune disease including but not limited to inflammatory bowel disease, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis, which requires systemic therapy in the past 2 years.
• •* Note: Patients with vitiligo, resolved childhood asthma/atopy, hypothyroidism on stable hormone replacement, controlled asthma, Type I diabetes, Graves' disease, or Hashimoto's disease, are not excluded.
• •History of grade ≥ 3 immune-related adverse events with previous immunotherapy. Note: Patients with adequately treated skin rash other than Steven-Johnson, toxic epidermal necrolysis of other severe forms of dermatitis; or replacement therapy for endocrinopathies, are not excluded.
• •History of interstitial lung disease or (non-infectious) pneumonitis that required steroids or current pneumonitis.
• •History of grade ≥ 3 allergic reaction to treatment with a monoclonal antibody.
• •Patients with Urinary Outflow Obstruction (apply to cyclophosphamide-based regimens only).