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Malignant Solid TumorPhase 1LUD2014-002NCT02252211

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

A Phase 1 study testing DS-8895a 1 mg/kg, DS-8895a 3 mg/kg and DS-8895a 10 mg/kg in people with Malignant Solid Tumor and Metastatic EphA2 Positive Cancer, run by Ludwig Institute for Cancer Research at 1 site in Australia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
DS-8895a 1 mg/kg, DS-8895a 3 mg/kg and DS-8895a 10 mg/kg
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
1 siteAustralia
Study dates
9 Dec 2014to 8 Sep 2016
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

1 site in 1 country.

Australia1 site

  • Austin Health

    Heidelberg, Victoria, 3084

Other trials in Australia

About this study

Official title: A Phase I Safety and Bioimaging Trial of DS-8895a in Patients With Advanced or Metastatic EphA2 Positive Cancers

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.

Read the detailed description

Patients received an initial ^89Zr trace-labelled infusion of DS-8895a on Day 1, followed by safety assessments, positron emission tomography (PET) imaging, and PK sampling over a 1-week period. DS-8895a was infused again on Days 8, 22, and 36. The Day 36 infusion of DS-8895a was also trace labelled with ^89Zr, with subsequent PET imaging and PK sampling. Four dose levels (1, 3, 10 and 20 mg/kg) were to be evaluated, with 3 to 6 patients entered at each dose level. Patients who responded or had stable disease per the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression, with restaging performed by computed tomography (CT) scans every 6 weeks.

Being tested
DS-8895a 1 mg/kg, DS-8895a 3 mg/kg, DS-8895a 10 mg/kg
Keywords
EphA2 positive cancer, DS-8895a monoclonal antibody

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DS-8895a 1 mg/kgDrug

    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.

  • DS-8895a 3 mg/kgDrug

    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.

  • DS-8895a 10 mg/kgDrug

    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.

Study groups in NCT02252211
Study groupRoleWhat they receive
DS-8895aExperimentalPatients received infusions with DS-8895a on Days 1, 8, 22, and 36. Infusions on Days 1 and 36 were trace labelled with ^89Zr (^89Zr-Df-DS-8895a). The Day 1 dose was 0.2 mg/kg, followed by subsequent doses calculated based on individual patient body weight and dosing cohort assignment.
Receives: Drug: DS-8895a 1 mg/kg; Drug: DS-8895a 3 mg/kg; Drug: DS-8895a 10 mg/kg

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Continuously for up to 58 weeks

Secondary outcomes (14)

  1. 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.

    Measured: Up to Day 43

  2. 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.

    Measured: Up to 58 weeks

  3. 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.

    Measured: Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)

  4. Mean Volume of Distribution at Steady State of ^89Zr-Df-DS-8895a Following the First Infusion

    The PK of ^89Zr-Df-DS-8895a was 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.

    Measured: Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)

  5. Mean Total Serum Clearance of ^89Zr-Df-DS-8895a Following the First Infusion

    The PK of ^89Zr-Df-DS-8895a was 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.

    Measured: Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)

  6. Mean Maximum Serum Concentration of ^89Zr-Df-DS-8895a Following the First Infusion

    The PK of ^89Zr-Df-DS-8895a was 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.

    Measured: Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)

  7. Mean Elimination Half-life of ^89Zr-Df-DS-8895a Following the First Infusion

    The PK of ^89Zr-Df-DS-8895a was 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.

    Measured: Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)

  8. Mean Area Under the Serum Concentration Curve of DS-8895a Following the First Infusion

    The PK of DS-8895a was calculated based on data from enzyme-linked immunosorbent assay (ELISA) of serum samples. Serum samples for ELISA were drawn at the same times as for gamma counting with the addition of Day 8 (pre- and 0 to 30 minutes post-infusion), Day 9 (anytime), and Day 22 (pre- and 0 to 30 minutes post-infusion). 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.

    Measured: Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)

  9. Mean Volume of Distribution at Steady State of DS-8895a Following the First Infusion

    The PK of DS-8895a was calculated based on data from enzyme-linked immunosorbent assay (ELISA) of serum samples. Serum samples for ELISA were drawn at the same times as for gamma counting with the addition of Day 8 (pre- and 0 to 30 minutes post-infusion), Day 9 (anytime), and Day 22 (pre- and 0 to 30 minutes post-infusion). 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.

    Measured: Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)

  10. Mean Total Serum Clearance of DS-8895a Following the First Infusion

    The PK of DS-8895a was calculated based on data from enzyme-linked immunosorbent assay (ELISA) of serum samples. Serum samples for ELISA were drawn at the same times as for gamma counting with the addition of Day 8 (pre- and 0 to 30 minutes post-infusion), Day 9 (anytime), and Day 22 (pre- and 0 to 30 minutes post-infusion). 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.

    Measured: Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)

  11. Mean Maximum Serum Concentration of DS-8895a Following the First Infusion

    The PK of DS-8895a was calculated based on data from enzyme-linked immunosorbent assay (ELISA) of serum samples. Serum samples for ELISA were drawn at the same times as for gamma counting with the addition of Day 8 (pre- and 0 to 30 minutes post-infusion), Day 9 (anytime), and Day 22 (pre- and 0 to 30 minutes post-infusion). 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.

    Measured: Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)

  12. Mean Elimination Half-life of DS-8895a Following the First Infusion

    The PK of DS-8895a was calculated based on data from enzyme-linked immunosorbent assay (ELISA) of serum samples. Serum samples for ELISA were drawn at the same times as for gamma counting with the addition of Day 8 (pre- and 0 to 30 minutes post-infusion), Day 9 (anytime), and Day 22 (pre- and 0 to 30 minutes post-infusion). 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.

    Measured: Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)

  13. Number of Patients With Pharmacodynamic (Metabolic) Response

    The pharmacodynamic (metabolic) response of DS-8895a was assessed by ^18F-FDG PET at Screening, Day 29, and Day 50. Tumor metabolism response was evaluated as the difference in standardized uptake values between the pre- and post-treatment FDG PET scans. The measurement of [18F]-FDG uptake for tumor metabolic response monitoring was performed according to the European Organization for Research and Treatment of Cancer (EORTC) PET response criteria (Young et al. Eur J Cancer 1999;35:1773-82).

    Measured: Day 29 and Day 50

  14. Number of Patients With Human Anti-Human Antibody Positivity

    Blood samples to detect human anti-human antibody (HAHA) formation were collected on Days 1 (pre-infusion [within 7 days of Day 1 dose] and post-infusion), 8, 22, 36 (pre-infusion), and 50 (anytime). For Cycle 2 onward, HAHA samples were collected on Day 1 (pre-infusion) and at the end of the study (anytime). HAHA samples were analyzed using ELISA and were categorized as either positive or negative for a HAHA response. HAHA positivity indicates that a patient has developed an antibody response.

    Measured: Up to 43 Weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Sep 2014 (estimated)
  2. Study start9 Dec 2014
  3. Primary completion8 Sep 2016
  4. Study completion8 Sep 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Model description
Patients were enrolled in sequential cohorts following a 3+3 dose-escalation scheme.
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02252211
Sponsor's protocol ID
LUD2014-002
Acronym
LUD2014-002
Status last verified
Oct 2022
First submitted
22 Sep 2014
Last updated
12 Oct 2022
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Gan HK, Parakh S, Lee FT, Tebbutt NC, Ameratunga M, Lee ST, O'Keefe GJ, Gong SJ, Vanrenen C, Caine J, Giovannetti M, Murone C, Scott FE, Guo N, Burvenich IJG, Paine C, Macri MJ, Kotsuma M, Senaldi G, Venhaus R, Scott AM. A phase 1 safety and bioimaging trial of antibody DS-8895a against EphA2 in patients with advanced or metastatic EphA2 positive cancers. Invest New Drugs. 2022 Aug;40(4):747-755. doi: 10.1007/s10637-022-01237-3. Epub 2022 Apr 11.

    PubMed 35404015

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing DS-8895a 1 mg/kg, DS-8895a 3 mg/kg and DS-8895a 10 mg/kg in people with Malignant Solid Tumor and Metastatic EphA2 Positive Cancer, run by Ludwig Institute for Cancer Research at 1 site in Australia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Mar 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Patients With Treatment-emergent Adverse Events (time frame: Continuously for up to 58 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02252211, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Oct 2022; AzTrials last refreshed its copy on 8 Nov 2026.

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