This phase I trial is evaluating a new intravenous drug treatment in patients with cancers that express a specific gene (NaPi2b), in particular patients with ovarian cancer or non-small cell lung cancerA Phase 1b, First-in-Human, Dose Escalation and Expansion Study of XMT-1536 In Patients With Solid Tumors Likely to Express NaPi2b

Inclusion

General Inclusion Criteria (for Dose Escalation, Expansion, and UPLIFT):

• ECOG performance status 0 or 1
• Measurable disease as per RECIST, version 1.1
• Resolution of all acute toxic effects of prior therapy or surgical procedures to ≤Grade 1 (except alopecia, stable immune-related toxicity such as hypothyroidism on hormone replacement, adrenal insufficiency on ≤10 mg daily prednisone [or equivalent], chronic Grade 2 peripheral sensory neuropathy after prior taxane therapy).
• Cardiac left ventricular ejection fraction (LVEF) ≥50% or ≥ the institution's lower limit of normal by either Echo or MUGA scan

• Adequate organ function as defined by the following criteria:

  1. Absolute neutrophil count (ANC) ≥1500 cells/mm3
  2. Platelet count ≥100,000/mm3
  3. Hemoglobin ≥9 g/dL
  4. In patients not on anticoagulation therapy: INR, activated partial thromboplastin time (aPTT), and prothrombin time (PT) all within 1.2 times the institution's upper limit of normal (ULN). Patients on anticoagulation therapy are allowed if their relevant laboratory values are within the therapeutic window.
  5. Estimated glomerular filtration rate (GFR) ≥45 mL/min
  6. Total bilirubin ≤ULN
  7. g. Patients with asymptomatic elevations in unconjugated bilirubin due to Gilbert syndrome or stable chronic hemolytic anemia (e.g., hereditary spherocytosis, sickle cell disease, thalassemia intermedia) may be eligible after discussion with the Sponsor Medical Monitor.
• Aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT) ≤1.5 times the institutional ULN.
• Albumin ≥3.0 g/dL
• Able to provide informed consent.

Ovarian Cancer Inclusion Criteria for UPLIFT:

• Histological diagnosis of high grade serous ovarian cancer, which includes fallopian tube, or primary peritoneal cancer, that is metastatic or recurrent.

• Platinum-resistant disease

  1. Patients who have only had 1 line of platinum-based therapy must have received at least 4 cycles of platinum, must have had a response [complete response/remission (CR) or partial response/remission (PR)], and then progressed between 3 months and ≤ 6 months after the date of the last dose of platinum
  2. Patients who have received 2 to 4 lines of prior therapy must have received at least 4 cycles of platinum and then progressed within 6 months after the date of the last dose of platinum

• One to 4 prior lines of systemic therapy for ovarian cancer

  a. Prior treatment with bevacizumab is required for patients with 1 to 2 prior lines of therapy

• Patients must be willing to provide an archival tumor tissue block or slides or if not available, undergo procedure to obtain a new tumor biopsy using a low-risk, medically routine procedure

Ovarian Cancer Inclusion Criteria for QTc sub-study:

Note: patients must meet all UPLIFT cohort inclusion criteria in order to participate in the QTc sub-study

• Study patient has agreed to remain in the clinic for the additional QTc related study activities on the Day 1 of Cycle 1 and Cycle 3.