Safety and Bioimaging Trial of DS-8895a in Patients With Advanced EphA2 Positive Cancers
Condition: Malignant Solid Tumor; Metastatic EphA2 Positive Cancer
Intervention: DS-8895a 1 mg/kg; DS-8895a 3 mg/kg; DS-8895a 10 mg/kg
Intervention description: Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 1 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 1 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.; Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 3 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 3 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.; Patients were to receive infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 10 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 10 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Sequential Assignment
Intervention model description: Patients were enrolled in sequential cohorts following a 3+3 dose-escalation scheme.
Masking: None (Open Label)
Enrollment: 9.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: EphA2 positive cancer; DS-8895a monoclonal antibody

Summary:

      This was a Phase 1, dose-escalation, non-randomized, open-label, single-center study of
      DS-8895a in patients with advanced or metastatic Ephrin type-A receptor 2 (EphA2)-positive
      cancers. The primary study objective was to determine the safety of DS-8895a, with secondary
      objectives of determining the biodistribution, tumor uptake (bioimaging), pharmacokinetics
      (PK), antitumor and pharmacodynamic response, and correlations between pharmacodynamics and
      clinical outcomes, as appropriate.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Advanced or metastatic EphA2 positive cancer (based on immunohistochemistry of
             archived or fresh tumor tissue).

          2. Malignant tumor that was refractory to standard treatment.

          3. At least one reference tumor > 1 cm in size for assessment of tumor uptake of
             ^89Zr-Df-DS-8895a.

          4. Expected survival of at least 3 months.

          5. Eastern Cooperative Oncology Group performance status ≤ 1.

          6. Within the last week prior to the first study drug administration, laboratory
             parameters for vital functions were to be in the normal range. Out-of-range values
             that were not clinically significant were permitted, except that the following
             parameters were to be in the specified ranges:

               -  Neutrophil count ≥ 1.5 x 10^9/L

               -  Platelet count ≥ 90 x 10^9/L

               -  International normalized ratio ≤ 1.5

               -  Serum aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x the upper
                  limit of normal (ULN); ≤ 5 x ULN if liver metastases

               -  Serum bilirubin ≤ 1.5 x ULN

          7. Calculated creatinine clearance ≥ 55 mL/min.

          8. Age ≥ 18 years.

          9. Able and willing to give valid written informed consent.

        Exclusion Criteria:

          1. Active central nervous system metastases. Definitively treated metastases were allowed
             if stable for 6 weeks off therapy.

          2. Known immunodeficiency or human immunodeficiency virus positivity.

          3. Serious illnesses, e.g., serious infections requiring antibiotics, bleeding disorders,
             or any condition that in the opinion of the Investigator would have interfered with
             the ability of the patient to fulfill the study requirements.

          4. Other malignancy, apart from non-melanoma skin cancer, within 3 years prior to the
             first study drug administration that in the opinion of the investigator had > 10% risk
             of relapse within 12 months.

          5. Significant allergic reaction to prior antibody infusions.

          6. Chemotherapy, radiotherapy, or investigational agent within 4 weeks prior to the first
             study drug administration.

          7. Regular corticosteroid, non-steroidal anti-inflammatory drug (other than paracetamol
             or low-dose aspirin) or other immunosuppressive treatment within 3 weeks prior to the
             first study drug administration (intermittent dosing permitted if less than 4 doses
             within a 3-day period).

          8. Mental impairment that could have compromised the ability to give informed consent and
             comply with the requirements of the study.

          9. Lack of availability for clinical follow-up assessments.

         10. Pregnancy or breastfeeding.

         11. Women of childbearing potential: Refusal or inability to use effective means of
             contraception.