A Randomised Phase II Open-label Study With a Phase Ib Safety lead-in Cohort of ONCOS-102, an Immune-priming GM-CSF Coding Oncolytic Adenovirus, and Pemetrexed/Cisplatin in Patients With Unresectable Malignant Pleural Mesothelioma

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02879669
• Date of registration: 13/07/2016
• Prospective Registration: No
• Primary sponsor: Targovax Oy
• Public title: A Randomised Phase II Open-label Study With a Phase Ib Safety lead-in Cohort of ONCOS-102, an Immune-priming GM-CSF Coding Oncolytic Adenovirus, and Pemetrexed/Cisplatin in Patients With Unresectable Malignant Pleural Mesothelioma
• Scientific title: A Randomised Phase II Open-label Study With a Phase Ib Safety lead-in Cohort of ONCOS-102, an Immune-priming GM-CSF Coding Oncolytic Adenovirus, and Pemetrexed/Cisplatin in Patients With Unresectable Malignant Pleural Mesothelioma
• Date of first enrolment: June 2016
• Target sample size: 31
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/show/NCT02879669
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

France, Spain

Key inclusion & exclusion criteria

Inclusion Criteria:

- Written informed consent.

- Male or female, =18 years of age.

- Histologically confirmed unresectable (advanced) malignant pleural mesothelioma in
patients who are not candidates for curative surgery and for whom therapy with
pemetrexed in combination with cisplatin or carboplatin is considered appropriate.
This include:

- patients who are naïve to chemotherapy,

- and those who have already received pemetrexed in combination with cisplatin or
carboplatin to which their tumour initially responded, but they have relapsed
after at least 6 months.

The patient may be evaluated by a multidisciplinary consultation (according to hospital
procedure), however the final decision about the inclusion of a patient is made by the
principal investigator.

- Measurable disease according to Response Evaluation in Solid Tumour (RECIST 1.1).

- Tumour must be accessible to intratumoural (i.t.) injections and to tumour core needle
biopsy or thoracoscopy for tissue sampling and immunohistochemistry analysis.

- The patients must be eligible to receive the study specific chemotherapies, including
cyclophosphamide, according to the SPCs and local practice.

- Eastern Cooperative Oncology Group (ECOG)/World Health Organization (WHO) performance
score 0 to 1.

- Acceptable liver, renal, and haematological functions.

- All women of childbearing potential must have a negative urine or serum pregnancy test
at screening and all patients must agree to use barrier contraception (i.e. condom)
during study treatment and for 2 months after the last virus treatment, 6 months after
the last dose of pemetrexed/cisplatin/carboplatin and 12 months after the dose of
cyclophosphamide.

Exclusion Criteria:

- Receipt of oncolytic virus treatment, or vaccination with a vaccine containing live
virus within 4 weeks before Day 1.

- Use of significant immunosuppressive medication, including high dose corticosteroid
(defined as the equivalent of >10 mg/day prednisone) within 4 weeks before Day 1.

- Patients who participated in a study with an investigational drug or device within 4
weeks prior to Day 1.

- Active bacterial, viral, or fungal infections, requiring systemic therapy.

- Severe arrhythmia, heart failure, previous cardiac infarction, or acute inflammatory
heart disease.

- Concomitant disease or condition that could interfere with the conduct of the study,
or that would, in the opinion of the Investigator, pose an unacceptable risk to the
patient, if included in this study.

- Known infection with HIV, hepatitis B, or hepatitis C.

- Known brain metastases.

- History of organ transplant.

- Females who are pregnant or breast feeding.

- Unwillingness or inability to comply with the study protocol for any reason.

- Patients with pre-existing hearing loss or neuropathy that may worsen due to potential
neurotoxicity from cisplatin.

- Patients with a history of hypersensitivity to cisplatin or carboplatin or pemetrexed
or cyclophosphamide (or any of its metabolites).

- Patients who are taking phenytoin for prophylactic use.

- History of malignant tumour, unless the patient has been without evidence of disease
for at least 3 years, or the tumour was a non-melanoma skin tumour, cervical carcinoma
in situ, or prostatic carcinoma in situ.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

To Determine Safety, Tolerability and Efficacy of ONCOS-102 in Combination With Chemotherapy

Intervention(s)

Biological: ONCOS-102

Drug: Cyclophosphamide

Drug: Pemetrexed/cisplatin (carboplatin)

Primary Outcome(s)

Number of patients with any (Serious and Non-Serious) Adverse Event measured to assess safety and tolerability [Time Frame: 6 months]

Secondary Outcome(s)

To analyse immunological activation by comparing patients with and without presence of tumour antigen recognizing CD8+ T cells [Time Frame: 6 months]

To determine and compare tumour-specific immunological activation in the peripheral blood in the experimental group and the control group. Number of patients in the respective arms with induction of Tumor specific CD8+ T Cells in PBMC [Time Frame: 6 months]

To determine and compare progression-free survival (PFS) in the experimental group and the control group by median time to progression in the respective arms [Time Frame: 6 months]

To analyse clinical outcome by time to event endpoints (OS and PFS) [Time Frame: 6 months]

To determine and compare overall survival (OS) in the experimental group and the control group [Time Frame: Until death]

To determine and compare immunological activation in tumour mass in the experimental group and the control Group. Number of patients in the respective arms with infiltration of CD8+ T Cells into tumours [Time Frame: 6 months]

To determine and compare overall response rate in the experimental group and the control group by number of patients with PD, SD, PR and CR in the respective arms [Time Frame: 6 months]

Secondary ID(s)

ONCOS C719

2015-005143-13

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Theradex