NCT02252211 - Safety and Bioimaging Trial of DS-8895a in Patients With Advanced EphA2 Positive Cancers | Crick

Eligibility

Sex: ALLMin age: 18 Years

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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.

Outcomes

Primary Outcomes

Number of Patients With Treatment-emergent Adverse Events

Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Treatment-emergent adverse events (TEAEs) were reported based on clinical laboratory tests, physical examinations, and vital signs from pre-treatment through the study period.

Time frame: Continuously for up to 58 weeks

Secondary Outcomes

Number of Patients With Tumor Uptake of ^89Zr-Df-DS-8895a

The biodistribution and tumor uptake of \^89Zr-Df-DS-8895a was determined based on qualitative analysis of whole body positron emission tomography (PET)/computed tomography (CT) images. PET imaging was performed following the \^89Zr-Df-DS-8895a infusions on Day 1 (Days 1, 4/5, and 7/8) and Day 36 (Days 36, 39/40 and 42/43). Qualitative parameters assessed included tumor uptake of reference lesions (scored on a 0-3 point scale: none, low, med, high). The reference lesions were initially identified on fluorodeoxyglucose (FDG) PET scans with a score of 3 for \[18F\]-fluorodeoxyglucose uptake. The summary table presents the maximum reference lesion \^89Zr-Df-DS-8895a uptake score reported for individual patients.

Time frame: Up to Day 43

Number of Patients With Best Overall Tumor Response

Tumor responses were evaluated using computed tomography and categorized according to the Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1) at Screening (up to 21 days before the first dose of study drug), on Day 50, and approximately every 6 weeks thereafter for patients who received continued study dosing. Per RECIST, target lesions are categorized as follows: Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD): ≥ 20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD): small changes that do not meet above criteria.

Time frame: Up to 58 weeks

Mean Area Under the Serum Concentration Curve of ^89Zr-Df-DS-8895a Following the First Infusion

The pharmacokinetics (PK) of \^89Zr-Df-DS-8895a were calculated based on data from gamma counting of serum samples. Serum samples for gamma counting were drawn on Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion), Day 2 (24 hours post-infusion), Day 4/5 (anytime), Day 36 (pre-infusion, and 5 minutes, 1, 2, and 4 hours post infusion), Day 37 (24 hours post-infusion), Day 39/40 (anytime), Day 42/43 (anytime), and Day 50 (anytime). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29.