Phase 1
Completed N=9
Safety and Bioimaging Trial of DS-8895a in Patients With Advanced EphA2 Positive Cancers
Malignant Solid Tumor · Metastatic EphA2 Positive Cancer
Source: ClinicalTrials.gov NCT02252211 ↗
Enrolled (actual)
9
Serious AEs
33.3%
Results posted
Mar 2019
Primary outcomePrimary: Number of Patients With Treatment-emergent Adverse Events — 4; 3; 0; 1 Participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Patients With Treatment-emergent Adverse Events |
4; 3; 0; 1; 4; 1 | — |
| SECONDARY Number of Patients With Tumor Uptake of ^89Zr-Df-DS-8895a |
0; 0; 4; 2; 0; 0 | — |
| SECONDARY Number of Patients With Best Overall Tumor Response |
1; 0; 0; 1 | — |
| SECONDARY Mean Area Under the Serum Concentration Curve of ^89Zr-Df-DS-8895a Following the First Infusion |
349.0; 486.5 | — |
| SECONDARY Mean Volume of Distribution at Steady State of ^89Zr-Df-DS-8895a Following the First Infusion |
64.3; 51.3 | — |
| SECONDARY Mean Total Serum Clearance of ^89Zr-Df-DS-8895a Following the First Infusion |
0.6; 0.5 | — |
| SECONDARY Mean Maximum Serum Concentration of ^89Zr-Df-DS-8895a Following the First Infusion |
3.1; 4.2 | — |
| SECONDARY Mean Elimination Half-life of ^89Zr-Df-DS-8895a Following the First Infusion |
77.4; 79.9 | — |
| SECONDARY Mean Area Under the Serum Concentration Curve of DS-8895a Following the First Infusion |
255.2; 391.0 | — |
| SECONDARY Mean Volume of Distribution at Steady State of DS-8895a Following the First Infusion |
51.8; 42.1 | — |
| SECONDARY Mean Total Serum Clearance of DS-8895a Following the First Infusion |
0.6; 0.5 | — |
| SECONDARY Mean Maximum Serum Concentration of DS-8895a Following the First Infusion |
3.0; 4.0 | — |
| SECONDARY Mean Elimination Half-life of DS-8895a Following the First Infusion |
59.3; 65.3 | — |
| SECONDARY Number of Patients With Pharmacodynamic (Metabolic) Response |
1; 0; 0; 1; 3; 2 | — |
| SECONDARY Number of Patients With Human Anti-Human Antibody Positivity |
1; 1; 3; 2 | — |
Eligibility Criteria
Inclusion Criteria
- Advanced or metastatic EphA2 positive cancer (based on immunohistochemistry of archived or fresh tumor tissue).
- Malignant tumor that was refractory to standard treatment.
- At least one reference tumor > 1 cm in size for assessment of tumor uptake of ^89Zr-Df-DS-8895a.
- Expected survival of at least 3 months.
- Eastern Cooperative Oncology Group performance status ≤ 1.
- 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
- Calculated creatinine clearance ≥ 55 mL/min.
- Age ≥ 18 years.
- Able and willing to give valid written informed consent.
Exclusion Criteria
- Active central nervous system metastases. Definitively treated metastases were allowed if stable for 6 weeks off therapy.
- Known immunodeficiency or human immunodeficiency virus positivity.
- 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.
- 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.
- Significant allergic reaction to prior antibody infusions.
- Chemotherapy, radiotherapy, or investigational agent within 4 weeks prior to the first study drug administration.
- 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).
- Mental impairment that could have compromised the ability to give informed consent and comply with the requirements of the study.
- Lack of availability for clinical follow-up assessments.
- Pregnancy or breastfeeding.
- Women of childbearing potential: Refusal or inability to use effective means of contraception.
Data sourced from ClinicalTrials.gov (NCT02252211). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.