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Non-Small Cell Lung CancerPhase 1NCT02824965

Pembrolizumab + CVA21 in Advanced NSCLC

A Phase 1 study testing Pembrolizumab and CVA21 in people with Non-Small Cell Lung Cancer, run by Olivia Newton-John Cancer Research Institute at 1 site in Australia.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

This will be a Phase Ib open-label trial of CAVATAK™ (CVA21) in combination with Pembrolizumab for the treatment of patients with advanced NSCLC. The dose of Pembrolizumab will be fixed at 200mg. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-Small Cell Lung Cancer
What is being tested?
Pembrolizumab and CVA21
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11 participants
Where
1 siteAustralia
Study dates
9 Aug 2017to Oct 2021
Phase
Phase 1
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

  • Be willing and able to provide written informed consent for the trial.
  • Be ≥ 18 years of age on day of signing informed consent.
  • Have measurable disease based on RECIST 1.1.
  • Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the Sponsor.
  • Have a performance status of 0 - 1 on the ECOG Performance Scale.
  • Histologically confirmed NSCLC.
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  • No CVA21 neutralising antibody (≤ 1:16).
  • Life expectancy > 3 months.
  • Acceptable haematological, renal and hepatic function.
  • Protocol approved by local Research Ethics Committees.
  • No chemotherapy, radiation therapy, hormonal treatment of immunotherapy within 28 days of dosing, except small doses of RT (<20 Gy) given for symptomatic bone metastases.
  • Have resolution of toxic effect(s) of the most recent prior chemotherapy to Grade 1 or less (except alopecia). If subject received major surgery or radiation therapy of > 30 Gy, they must have recovered from the toxicity and/or complications from the intervention.
  • Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Female subjects of childbearing potential must be willing to use an adequate method of contraception as outlined in section 6.13.2, starting with the first dose of study drug therapy through 120 days after the last dose of study therapy.
  • Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
  • Male subjects of child-bearing potential must agree to use an adequate method of contraception outlined in section 6.13.2, starting with the first dose of study therapy through 120 days after the last dose of study therapy.
  • Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
  • Failed at least one line of standard chemotherapy or tyrosine kinase inhibitor (TKI) as treatment for Stage IV NSCLC. Patients with EGFR mutations or ALK gene rearrangements are eligible only after initial TKI failure and chemotherapy is not felt to be a suitable option by the investigator.

Who cannot join

  • Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
  • Has a known history of active TB (Bacillus Tuberculosis)
  • Hypersensitivity to pembrolizumab or any of its excipients.
  • Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
  • Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
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  • Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
  • Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
  • Has active cardiac disease.
  • Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability.
  • Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • Has known history of, or any evidence of active, non-infectious pneumonitis.
  • Has a history of interstitial lung disease.
  • Has an active infection requiring systemic therapy.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
  • Has previously received treatment with CVA21.
  • Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  • Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  • Has received a live vaccine within 30 days of planned start of study therapy.

Trial locations and contacts

1 site in 1 country.

Australia1 site

  • Austin Health

    Heidelberg, Victoria, 3078

Other trials in Australia

About this study

Official title: A Phase I/II Open-label Trial of Intravenous CAVATAK^TM in Combination With Pembrolizumab for the Treatment of Patients With Advanced NSCLC

This will be a Phase Ib open-label trial of CAVATAK™ (CVA21) in combination with Pembrolizumab for the treatment of patients with advanced NSCLC. The dose of Pembrolizumab will be fixed at 200mg. Three cohorts (dose levels) of intravenously-delivered CVA21 will be explored, using a standard 3+3 patient dose escalation design. The starting dose of CVA21 will be one log below the 1 x 10^9 TCID50 dose found to be safe when CVA21 was given alone in an ongoing Phase I study (NCT02043665).

Read the detailed description

Primary Objective \& Hypothesis

(1) Objective:

To evaluate the safety of intravenous CVA21 in combination with pembrolizumab in patients with advanced NSCLC.

Hypothesis:

Pembrolizumab in combination with intravenous CVA21 will be well tolerated in patients with advanced NSCLC.

Secondary Objective \& Hypothesis

(1) Objective:

  1. To evaluate the efficacy of intravenous CVA21 in inducing an immune cell rich tumour microenvironment in patients with a baseline biopsy demonstrating a tumour with an immune cell poor microenvironment. ii. To evaluate the efficacy of intravenous CVA21 in combination with pembrolizumab in patients with advanced NSCLC using irRECIST. iii. To evaluate the safety of intravenous CVA21 in combination with pembrolizumab. iv. To identify a safe and potentially effective dose for intravenous CVA21 in combination with intravenous pembrolizumab.
  2. To serially evaluate the presence of detectable virus and anti-viral antibodies in peripheral blood of the trial participants.

Hypothesis:

  1. CVA21 will induce immune cell infiltration into tumors of patients that lack an immune cell rich micro-environment.
Being tested
Pembrolizumab, CVA21
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

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

  • PembrolizumabDrug

    Also called KEYTRUDA

    Pembrolizumab is a selective monoclonal antibody that blocks the interaction between PD1 and its ligands PDL1 and PDL2, resulting in infiltration of tumour specific CD8+ T-cells and ultimately leads to tumour rejection.

  • CVA21Biological

    Also called CAVATAK, Coxsackie virus 21

    CAVATAK is an oncolytic Coxsackie virus that specifically infects and kills ICAM overexpressing tumour cells

Study groups in NCT02824965
Study groupRoleWhat they receive
Pembrolizumab+1x10^9 TCID50 CVA21ExperimentalCVA21 will be administered IV on days: 1, 3, 5, 8 29, 50, 71, 92, 113 134, and 155. 200mg Pembrolizumab will be administered as per normal dosing frequency at Q3W IV, and will continue for up to 24 months. Should dose limiting toxicities be observed participants may be transferred a lower dosage of CVA21.
Receives: Drug: Pembrolizumab; Biological: CVA21

What is being measured

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

  1. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability].

    To evaluate the safety of intravenous CVA21 in combination with pembrolizumab in patients with advanced NSCLC. All adverse events will be collected and assessed with regards to CTCAE V4.0 grading, seriousness, duration and relationship to the study drugs.

    Measured: 0-24 months

Secondary outcomes (6)

  1. ORR from the date of first study treatment as assessed by RECIST

    Quantification of the Objective Response rate in patients on study by RECIST

    Measured: 0-24 months

  2. ORR from the date of first study treatment as assessed by immune related response criteria (irRC)

    The overall response according to the irRC is derived from time-point response assessments based on tumor burden. In the irRC, an immune-related Complete Response (irCR) is the disappearance of all lesions, measured or unmeasured, and no new lesions; an immune-related Partial Response (irPR) is a 50% drop in tumour burden from baseline as defined by the irRC; and immune-related Progressive Disease (irPD) is a 25% increase in tumour burden from the lowest level recorded. Everything else is considered immune-related Stable Disease (irSD).

    Measured: 0-24 Months

  3. PFS

    Progression Free survival from first study treatment until end of study

    Measured: 0-36 Months

  4. Incidence of detectable CVA21 virus and neutralizing antibodies

    Measurement of CVA21 virus and neutralizing antibodies at each CVA21 injection time point

    Measured: 0-24 Months

  5. OS

    Overall survival of patients on study from first study treatment.

    Measured: 0-36 Months

  6. Change in PD-L1 expression from sequential biopsies in NSCLC patients

    PD-L1 expression will be measured using IHC from baseline and sequential biopsies

    Measured: 0-36 months

Timeline

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

  1. First posted7 Jul 2016 (estimated)
  2. Study start9 Aug 2017
  3. Primary completion1 Jul 2021
  4. Study completionOct 2021 (estimated)

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
Single group
Masking
None (open label)
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02824965
Sponsor's protocol ID
ONJ2015-001
Status last verified
Jul 2021
First submitted
13 Jun 2016
Last updated
7 Jul 2021
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 1 study testing Pembrolizumab and CVA21 in people with Non-Small Cell Lung Cancer, run by Olivia Newton-John Cancer Research Institute 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 18 inclusion and 22 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: status not confirmed, as of the sponsor's last update on 7 Jul 2021. 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?

Results are not available in the source record.

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?

Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]. (time frame: 0-24 months). 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 NCT02824965.

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 7 Jul 2021.

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