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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02824965




Registration number
NCT02824965
Ethics application status
Date submitted
13/06/2016
Date registered
7/07/2016
Date last updated
7/07/2021

Titles & IDs
Public title
Pembrolizumab + CVA21 in Advanced NSCLC
Scientific title
A Phase I/II Open-label Trial of Intravenous CAVATAK^TM in Combination With Pembrolizumab for the Treatment of Patients With Advanced NSCLC
Secondary ID [1] 0 0
ONJ2015-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-Small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Non small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Pembrolizumab
Other interventions - CVA21

Experimental: Pembrolizumab+1x10^9 TCID50 CVA21 - CVA21 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.


Treatment: Drugs: Pembrolizumab
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.

Other interventions: CVA21
CAVATAK is an oncolytic Coxsackie virus that specifically infects and kills ICAM overexpressing tumour cells
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability].
Timepoint [1] 0 0
0-24 months
Secondary outcome [1] 0 0
ORR from the date of first study treatment as assessed by RECIST
Timepoint [1] 0 0
0-24 months
Secondary outcome [2] 0 0
ORR from the date of first study treatment as assessed by immune related response criteria (irRC)
Timepoint [2] 0 0
0-24 Months
Secondary outcome [3] 0 0
PFS
Timepoint [3] 0 0
0-36 Months
Secondary outcome [4] 0 0
Incidence of detectable CVA21 virus and neutralizing antibodies
Timepoint [4] 0 0
0-24 Months
Secondary outcome [5] 0 0
OS
Timepoint [5] 0 0
0-36 Months
Secondary outcome [6] 0 0
Change in PD-L1 expression from sequential biopsies in NSCLC patients
Timepoint [6] 0 0
0-36 months

Eligibility
Key inclusion criteria
1. Be willing and able to provide written informed consent for the trial.

2. Be = 18 years of age on day of signing informed consent.

3. Have measurable disease based on RECIST 1.1.

4. 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.

5. Have a performance status of 0 - 1 on the ECOG Performance Scale.

6. Histologically confirmed NSCLC.

7. No CVA21 neutralising antibody (= 1:16).

8. Life expectancy > 3 months.

9. Acceptable haematological, renal and hepatic function.

10. Protocol approved by local Research Ethics Committees.

11. 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.

12. 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.

13. 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.

14. 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.

15. 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.

16. 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. 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.

2. 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.

3. Has a known history of active TB (Bacillus Tuberculosis)

4. Hypersensitivity to pembrolizumab or any of its excipients.

5. 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.

6. 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.

- 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.

7. Has active cardiac disease.

8. 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.

9. 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.

10. 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.

11. Has known history of, or any evidence of active, non-infectious pneumonitis.

12. Has a history of interstitial lung disease.

13. Has an active infection requiring systemic therapy.

14. 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.

15. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.

16. 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.

17. Has previously received treatment with CVA21.

18. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

19. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
[qualitative] is detected).

20. Has received a live vaccine within 30 days of planned start of study therapy.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Unknown status
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
9/08/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/10/2021
Actual
Sample size
Target
Accrual to date
Final
11
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Austin Health - Heidelberg
Recruitment postcode(s) [1] 0 0
3078 - Heidelberg

Funding & Sponsors
Primary sponsor type
Other
Name
Olivia Newton-John Cancer Research Institute
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Merck Sharp & Dohme LLC
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/Industry
Name [2] 0 0
Viralytics
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief 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. 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).
Trial website
https://clinicaltrials.gov/ct2/show/NCT02824965
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Thomas John
Address 0 0
Austin Health
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02824965