Clinical Trials

Inclusion Criteria:

• Age ≥18 years.
• ECOG Performance Status (PS) 0-1 (Appendix I).
• Histologically confirmed surgical diagnosis of stage IIIC or stage IV epithelial ovarian, fallopian tube, or primary peritoneal cancer. Patients with stage III cancer must have had peritoneal metastasis beyond pelvis more than 1 cm in greatest dimension and/or regional lymph node metastasis. NOTE: Histologic confirmation of the primary tumor is required. Eligible histologies include serous, endometrioid, clear cell, mucinous, transitional cell, undifferentiated, or mixed carcinoma.
• MUC1 expression in ovarian cancer tumor cells verified by immunohistochemistry (IHC) in a CLIA laboratory. Heterogeneous tumor expression of MUC1 is acceptable. See section 14.0.
• Relapsed or refractory ovarian cancer previously treated with or intolerant to at least one prior line of therapy with platinum chemotherapy and be relapsed or have tumor evaluable for response if in first line setting resistant or intolerant to platinum. Patients with BRCA1/2 mutations must have received prior treatment with a PARP inhibitor to be eligible.
• Platinum-resistance is defined as any of the following occurring <183 days after the last dose of platinum-based chemotherapy:
  • Development of measurable disease (per RECIST 1.1);
  • Progression of radiographic disease (per RECIST 1.1);
  • Increase in CA-125 level to ≥2 × ULN (if WNL at the completion of platinum-based chemotherapy);
  • Increase in CA-125 level to ≥2 × nadir (if nadir >ULN).

If CA-125 is used to determine the date of progression then it must be confirmed by a second CA-125 value ≥7 days after the first level. The date of the first qualifying CA-125 is used to compute the platinum-free interval

• Patients must have measurable disease per RECIST criteria on study entry, which must include at least 1 lesion that has a single diameter of >1 cm measured by CT or MRI or the CT portion of the PET/CT.
  • Skin lesions can be used if the area is >1cm in at least one diameter and measured with a ruler.
• Expected survival unless investigational therapy is effective is greater than 6 months but less than 24 months.
• Willingness and ability to provide written informed consent.
• Willing to return to MCA for follow-up during the Active Monitoring Phase of the study.
• Willingness to provide mandatory blood specimens and biopsy tissue for correlative research (see Section 14.0).
• Willing to undergo leukapheresis for blood component collection.
• The following laboratory parameters (paid by patient insurance) must be performed ≤14 days prior to registration:
  • Absolute neutrophil count (ANC) ≥1500/mm3;
  • Lymphocyte count ≥ 500/mm3;
  • Hemoglobin ≥ 8.0 g/dL;
  • Platelet count ³30,000/mm3;
  • Total bilirubin ≤2.0 mg/dL unless patient has documented Gilbert’s syndrome (Subjects with Gilbert’s Syndrome may be included if their total Bilirubin is ≤3.0 x ULN and direct bilirubin ≤1.5 x ULN);
  • Alanine aminotransferase (ALT) and aspartate amino transferase  (AST) £3 x ULN (≤5 x ULN for patients with liver involvement of their cancer);
  • PT, INR and aPTT ≤1.5 x ULN OR if patient is receiving anticoagulation therapy and INR or aPTT is within target range of therapy (for patients receiving anticoagulation, there should be no prior history of bleeding and no recent DVT/PE within the last 6 months of enrollment);
  • Calculated creatinine clearance ≥30 ml/min using the Cockcroft-Gault.
• Baseline oxygen saturation ≥90% on room air.
• For patients enrolled in dose level 3, prior to receiving the second infusion the following conditions must be met:
  • All grade 3 non-hematologic AE must be recovered to grade 1 or lower
  • All hematologic AEs must be recovered to grade 2 or lower;.

NOTE: Hemoglobin, leukocyte, and platelet values may be reduced from baseline, but not greater than grade 2, as would be expected from lymphodepleting chemotherapy received prior to infusion 1.

Exclusion criteria

• Clinically unresolved CNS metastases.

NOTE: Patients with a prior history of brain metastases are allowed if focally treated, radiographically stable for > 30 days, and not requiring steroid therapy for > 14 days.

• Prior treatment targeting MUC1.
• Subjects with known plasma cell leukemia (PCL)
• Any of the following are excluded because this study involves an agent (CTX) that has known genotoxic, mutagenic and/or teratogenic effects:
  • Pregnant persons;
  • Nursing persons;
  • Persons of childbearing potential who are unwilling to employ adequate birth control measures,
• History of myocardial infarction ≤6 months prior to registration, and/or congestive heart failure requiring ongoing treatment such as medications and/or an implanted defibrillator to control life-threatening arrhythmias.
• Failure to recover to grade 1 or baseline from acute, reversible effects of prior therapy regardless of interval since last treatmeny.
• EXCEPTION: Grade 2 peripheral (sensory) neuropathy that has been stable for at least 3 months since completion of prior treatment.

NOTE: See eligibility criteria in 3.1.14 for exceptions related to repeat dosing in dose level 3

• Uncontrolled concurrent illness including, but not limited to:
  • inability to clear an ongoing or active infection;
  • symptomatic congestive heart failure;
  • unstable angina pectoris;
  • uncontrolled psychiatric problems and/or difficult social situation;
  • dyspnea at rest due to complications of advanced malignancy or other disease that requires continuous oxygen therapy;
  • any other conditions that the protocol investigators deem could potentially limit compliance with study requirements.
• Evidence of clinical immunocompromise and/or HIV positivity and currently receiving antiretroviral therapy.
• Patients requiring chronic supraphysiologic daily doses of steroids (> 10 mg prednisone or prednisolone, ≥ 4 mg Decadron or ≥ 50 mg hydrocortisol daily).
• Patients receiving any other investigational agent which could be considered a treatment for the neoplasm.
• Other active malignancy first documented ≤ 4 years prior to registration. EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix.

NOTE: If there is a history of other malignancy, the patient must not be receiving other treatment aimed at suppressing its recurrence.

• Diagnosis of autoimmune disease, including, but not limited to:
  • Systemic lupus erythematosus (lupus);
  • Multiple sclerosis (MS);
  • Rheumatoid arthritis (RA);
  • Ankylosing spondylitis;
  • Other autoimmune disease (specify).

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 2/29/2024. Questions regarding updates should be directed to the study team contact.