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Non Small Cell Lung CancerPhase 2DOMINATIONNCT04262375

A Phase 2 Study of Durvalumab (MEDI4736) and Oleclumab (MEDI9447) in Multi-Cancer Populations With Correlation to Clinical, Molecular and Immunologic Parameters With DNA MethylaTION

A Phase 2 study testing Durvalumab and Oleclumab in people with Non Small Cell Lung Cancer and Renal Cell Carcinoma, run by University Health Network, Toronto at 1 site in Canada.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This is a Phase II, prospective, non-randomized, open-label trial involving cancer patients with known inflamed tumor types. Patients with previously treated advanced/metastatic non-small cell lung cancer or renal cell cancer will be recruited in near equal distribution. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Durvalumab and Oleclumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteCanada
Study dates
Jan 2021to Jan 2024
Phase
Phase 2
Are there results?
None posted in the registry

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

  • Age ≥ 18 years at the time of screening or age of consent according to law
  • Life expectancy of at least 12 weeks
  • Written informed consent and any locally required authorization obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
  • ECOG 0 or 1
  • Weight ≥35kg
  • Subjects diagnosed with histologically or cytologically confirmed non small cell lung (NSCLC) or renal cell carcinoma (RCC)
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  • Subjects must have at least 1 measurable lesion according to RECIST version 1.1.
  • Archival tumor formalin-fixed, paraffin-embedded (FFPE) specimens for correlative biomarker studies are required (1 H\&E and 15 unstained slides). Subjects with insufficient archived tumor samples are still eligible, pending discussion with the principal investigator on a case by case basis
  • Adequate organ and marrow function
  • Females of childbearing potential who are sexually active with a nonsterilized male partner must use at least one highly effective method of contraception from screening to 90 days after the final dose of study treatment
  • Nonsterilized male subjects who are sexually active with a female partner of childbearing potential must use a male condom with spermicide from screening to 90 days after receipt of the final dose of study treatment

Who cannot join

  • Receipt of any conventional or investigational anticancer therapy within 21 days or palliative radiotherapy within 14 days prior to the scheduled first dose of study treatment
  • Prior receipt of any agents targeting CD73, including patients treated with adenosine receptor antagonists, CD39 or CD73 inhibitors
  • Prior receipt of any innate immune agonists
  • Patients with NSCLC with known activating EGFR mutations or ALK translocations
  • Concurrent enrollment in another therapeutic clinical study. Enrollment in observational studies will be allowed
  • Any toxicity (excluding alopecia) from prior standard therapy that has not been completely resolved to baseline at the time of consent
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  • Subjects with a history of Grade 3 or greater thromboembolic events in the prior 12 months or thromboembolic event of any grade with ongoing symptoms
  • Subjects with prior history of myocardial infarction, transient ischemic attack, congestive heart failure ≥ Class 3 based on New York Heart Association Functional Classification or stroke within the past 3 months prior to the scheduled first dose of study treatment
  • Active or prior documented autoimmune disorders within the past 3 years prior to the scheduled first dose of study treatment
  • HIV, Hep A, B, or C
  • History of primary immunodeficiency, solid organ transplantation, or active tuberculosis
  • Known allergy or hypersensitivity to investigational product formulations
  • History of more than one event of infusion related reactions (IRR) requiring permanent discontinuation of IV drug treatment
  • Active grade 3 or greater edema
  • History of Grade 3 or greater thromboembolic events in the prior 12 months or thromboembolic event of any grade with ongoing symptoms
  • Uncontrolled intercurrent
  • Any history of untreated leptomeningeal disease or cord compression
  • Untreated CNS metastatic disease
  • Current or prior use of immunosuppressive medication within 14 days prior to the scheduled first dose of study treatment
  • Receipt of live, attenuated vaccine within 30 days prior to the scheduled first dose of study treatment
  • Major surgery within 28 days prior to scheduled first dose of study treatment or still recovering from prior surgery
  • Females who are pregnant, lactating, or intend to become pregnant during their participation in the study
  • Subjects who are involuntarily incarcerated or are unable to willingly provide consent or are unable to comply with the protocol procedures
  • Any condition that would interfere with the evaluation of the study regimen or interpretation of patient safety or study results
  • Any condition that would interfere with safe administration or evaluation of the investigational products or interpretation of subject safety or study results

Trial locations and contacts

1 site in 1 country.

Canada1 site

  • Princess Margaret Cancer Centre

    Toronto, Ontario, M5G 2M9

Other trials in Canada

About this study

Official title: A Phase 2 Study of Durvalumab (MEDI4736) and Oleclumab (MEDI9447) in Multi-Cancer Populations With Correlation to Clinical, Molecular and Immunologic Parameters With DNA MethylaTION (DOMINATION)

This is a Phase II, prospective, non-randomized, open-label trial involving cancer patients with known inflamed tumor types. Patients with previously treated advanced/metastatic non-small cell lung cancer or renal cell cancer will be recruited in near equal distribution. All patients must have documented response or prolonged stable disease to previous immunotherapy. At present, we plan to enrol 55 patients, to be treated with durvalumab and oleclumab. The regimen will consist of durvalumab 1500 mg given by vein every 4 weeks and oleclumab 3000 mg given by vein every 2 weeks x 4 doses then IV every 4 weeks till disease progression, withdrawal of subject consent, or another reason for discontinuation. Estimated total duration from time to first subjects consent to last subject's last visit is approximately 36 months.

Read the detailed description

Study Hypotheses:

  1. Circulating free methylated DNA immunoprecipitation and high-throughput sequencing (cfMeDIP-seq) can yield cancer type-agnostic predictive biomarker(s) of response and/or toxicity in subjects receiving this combination.
  2. The combination of oleclumab (anti-cluster of differentiation [CD]73 monoclonal antibody) with durvalumab (anti programmed cell death ligand 1 [PD-L1]) will demonstrate adequate safety, tolerability, and antitumor activity in subjects with metastatic non-small-cell lung cancer (NSCLC) and renal cell cancer (RCC) previously treated with checkpoint inhibitors.
Being tested
Durvalumab, Oleclumab
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Carcinoma, Renal Cell

What participants receive

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

  • DurvalumabBiological

    Also called IMFINZI

    Durvalumab is a human immunoglobulin G (IgG)1 kappa monoclonal antibody directed against human PD-L1. Durvalumab selectively binds human PD-L1 with high affinity and blocks its ability to bind to PD-1 and cluster of differentiation (CD)80. The fragment crystallizable (Fc) domain of durvalumab contains a triple mutation in the constant domain of the IgG1 heavy chain that reduces binding to the complement component C1q and the Fc gamma receptors responsible for mediating antibody dependent cell mediated cytotoxicity.

  • OleclumabBiological

    Oleclumab is a human immunoglobulin G1 lambda monoclonal antibody (mAb) with a triple mutation in the heavy chain constant region for reduced effector function. Oleclumab selectively binds to cluster of differentiation 73 (ecto-5'-nucleotidase) (CD73) and inhibits CD73-associated ectonucleotidase activity, thereby inhibiting the CD73-mediated production of immunosuppressive adenosine. Extracellular adenosine contributes to the immunosuppressive effects of both regulatory T cells and myeloid derived suppressor cells, among others. This, in turn, leads to increased antitumor immunity.

Study groups in NCT04262375
Study groupRoleWhat they receive
Durvalumab and OleclumabExperimentalA single dose level for oleclumab and durvalumab will be used, comprising of Oleclumab 3000 mg IV Q2W for 4 doses, then Q4W AND Durvalumab 1500 mg IV Q4W
Receives: Biological: Durvalumab; Biological: Oleclumab

What is being measured

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

  1. Association between cfMeDIP and Response (defined as either complete response, partial response, or stable disease ≥ 4 cycles, as per RECIST 1.1. Association between cfMeDIP and Toxicity (defined as ≥ Grade 2 immune- adverse event (AE) as per CTCAE 5.0).

    To identify cfMeDIP-seq-based predictive signature(s) that are correlated with specific outcome to durvalumab and oleclumab such as response/resistance or occurrence of toxicity in non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC)

    Measured: 3 years

  2. Objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

    Measured: 3 years

  3. Disease control rate (DCR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

    Measured: 3 years

  4. Duration of response (DoR)

    Measured: 3 years

Secondary outcomes (2)

  1. Incidence of treatment-emergent adverse events (AEs)

    To assess the safety and tolerability of durvalumab and oleclumab in specific disease states in NSCLC and RCC

    Measured: 3 years

  2. Overall survival (OS) or progression-free survival (PFS)

    Measured: 3 years

Timeline

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

  1. First posted10 Feb 2020
  2. Study startJan 2021 (estimated)
  3. Primary completionJan 2024 (estimated)
  4. Study completionJan 2024 (estimated)

Why it stopped: Overall clinical activity (ORR) for oleclumab + durvalumab is minimal across tumor types and does not support further evaluation of this doublet.

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04262375
Sponsor's protocol ID
DOMINATION
Other IDs
19-6281
Acronym
DOMINATION
Status last verified
Nov 2020
First submitted
5 Feb 2020
Last updated
17 Nov 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Durvalumab and Oleclumab in people with Non Small Cell Lung Cancer and Renal Cell Carcinoma, run by University Health Network, Toronto at 1 site in Canada.

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 11 inclusion and 25 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: withdrawn, as of the sponsor's last update on 17 Nov 2020. 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 Canada. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

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?

Association between cfMeDIP and Response (defined as either complete response, partial response, or stable disease ≥ 4 cycles, as per RECIST 1.1. Association between cfMeDIP and Toxicity (defined as ≥ Grade 2 immune- adverse event (AE) as per CTCAE 5.0). (time frame: 3 years). The study lists 4 primary outcomes in all. 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 NCT04262375.

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 17 Nov 2020.

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