ONCOS-C719

Targovax Oy

Lars Sonckin kaari 14, Espoo, Finland, FI-02600

Dr. Lone H. Ottesen, Targovax, +44 7920567911, lone.ottesen@targovax.com

Dr. Lone H. Ottesen, Targovax, +44 7920567911, lone.ottesen@targovax.com

No

No

No

Final

11 Nov 2021

Yes

08 Oct 2019

Yes

08 Oct 2019

No

To determine the safety and tolerability of ONCOS-102 in combination with the standard of care treatment: pemetrexed plus either cisplatin or carboplatin. Safety was assessed per standard procedures i.e., evaluation of Adverse Events, laboratory test results, and vital signs. In addition, viral shedding was assessed in this study.

Visits schedule designed to monitor patients safety and treatment efficacy. Patient Confidentiality The Investigator(s) will respect and protect the confidentiality of the patient in all possible ways. Patient identification, other than the patient’s study number, and date of birth, will not appear in any eCRF pages or other documents given to the Sponsor. Only the Investigator and the persons authorised to verify the quality and integrity of the study data will have an access to patient records where the patient can be identified. Insurance The Sponsor was responsible for insuring all study subjects against any harm caused by study procedures or investigational product.

17 Jun 2016

Yes

Yes

Spain: 26

France: 5

31

31

0

0

0

0

0

0

10

21

0

Phase 2 with a Phase 1b lead-in cohort (overall period)

Randomised - controlled

Not applicable

Yes

ONCOS-102

Concentrate for solution for injection

Intratumoral use

ONCOS-102 was administered in a priming cycle which comprised of injections on Days 1, 4, 8, and 36, followed by 2 treatment cycles at intervals of 6 weeks (Day 78 and Day 120) at a dose of 3 x 10^11 virus particles (VP).

Cyclophosphamide

CPO

Powder for solution for injection

Intravenous use

Eligible patients were pre-treated with an intravenous (i.v.) bolus injection of CPO between 1 and 3 days before the first administration of ONCOS-102. Patients received a second pre-treatment with CPO between 1 and 3 days before administration of ONCOS-102 on Day 78. CPO was to be administered as an i.v. bolus of 300 mg/m2 (dose could have been reduced if deemed necessary by the investigator).

Cisplatin

Concentrate for solution for infusion

Intravenous use

All patients were to receive chemotherapy in 21-day cycles. The recommended dose of cisplatin was 75 mg/m2 infused i.v. over 2 hours beginning approximately 30 minutes after the end of pemetrexed infusion. Doses of cisplatin could have been reduced if deemed necessary by the investigator.

Pemetrexed

PEMETREXED DISODIUM

Powder for concentrate for solution for injection/infusion

Intravenous use

Pemetrexed was administered in combination with cisplatin or carboplatin as standard of care in 21-day cycles starting on Day 22. Pemetrexed 500 mg/m2 was to be administered as an intravenous infusion over 10 minutes on Day 1 of each 21-day cycle. Doses of pemetrexed could have been reduced if deemed necessary by the investigator.

Carboplatin

Concentrate for solution for infusion

Intravenous use

Patients received standard of care pemetrexed in combination with carboplatin (or cisplatin if appropriate) in 21-day cycles starting on Day 22. The dose of carboplatin was to be calculated based on the glomerular filtration rate calculated as per standard practice at the study. Patients were to receive carboplatin AUC 5. Doses of carboplatin could have been reduced if deemed necessary by the investigator.

Cisplatin

Concentrate for solution for infusion

Intravenous use

All patients were to receive chemotherapy in 21-day cycles. The recommended dose of cisplatin was 75 mg/m2 infused i.v. over 2 hours beginning approximately 30 minutes after the end of pemetrexed infusion. Doses of cisplatin could have been reduced if deemed necessary by the investigator.

Pemetrexed

PEMETREXED DISODIUM

Powder for concentrate for solution for injection/infusion

Intravenous use

Pemetrexed was administered in combination with cisplatin or carboplatin as standard of care in 21-day cycles starting on Day 22. Pemetrexed 500 mg/m2 was to be administered as an intravenous infusion over 10 minutes on Day 1 of each 21-day cycle. Doses of pemetrexed could have been reduced if deemed necessary by the investigator.

Carboplatin

Concentrate for solution for infusion

Intravenous use

Patients received standard of care pemetrexed in combination with carboplatin (or cisplatin if appropriate) in 21-day cycles starting on Day 22. The dose of carboplatin was to be calculated based on the glomerular filtration rate calculated as per standard practice at the study. Patients were to receive carboplatin AUC 5. Doses of carboplatin could have been reduced if deemed necessary by the investigator.

Phase 2 with a Phase 1b lead-in cohort

Experimental Group

Patients were pre-treated with an intravenous (i.v.) bolus injection of CPO between 1 and 3 days before the first administration of ONCOS-102. ONCOS-102 was administered in a priming cycle which comprised of injections on Days 1, 4, 8, and 36, followed by 2 treatment cycles at intervals of 6 weeks (Day 78 and Day 120) at a dose of 3 x 10^11 virus particles (VP). Patients received a second pre-treatment with CPO between 1 and 3 days before administration of ONCOS-102 on Day 78. Patients also received standard of care pemetrexed in combination with either cisplatin or carboplatin in 21-day cycles starting on Day 22. Patients were given vitamin supplementation with folic acid and vitamin B12, and dexamethasone according to the Summary of Product Characteristics (SmPC) and/or local guidelines.

Control Group

Patients received pemetrexed in combination with either cisplatin or carboplatin in 21-day cycles and continued treatment as applicable during the study period of 6 cycles of chemotherapy. Patients in the Control Group did not receive ONCOS-102. Patients were given vitamin supplementation with folic acid and vitamin B12, and dexamethasone according to the SmPC and/or local guidelines.

Experimental Group

Control Group

Experimental Group

Patients were pre-treated with an intravenous (i.v.) bolus injection of CPO between 1 and 3 days before the first administration of ONCOS-102. ONCOS-102 was administered in a priming cycle which comprised of injections on Days 1, 4, 8, and 36, followed by 2 treatment cycles at intervals of 6 weeks (Day 78 and Day 120) at a dose of 3 x 10^11 virus particles (VP). Patients received a second pre-treatment with CPO between 1 and 3 days before administration of ONCOS-102 on Day 78. Patients also received standard of care pemetrexed in combination with either cisplatin or carboplatin in 21-day cycles starting on Day 22. Patients were given vitamin supplementation with folic acid and vitamin B12, and dexamethasone according to the Summary of Product Characteristics (SmPC) and/or local guidelines.

Control Group

Patients received pemetrexed in combination with either cisplatin or carboplatin in 21-day cycles and continued treatment as applicable during the study period of 6 cycles of chemotherapy. Patients in the Control Group did not receive ONCOS-102. Patients were given vitamin supplementation with folic acid and vitamin B12, and dexamethasone according to the SmPC and/or local guidelines.

All AEs are categorised as baseline findings or treatment emergent AEs (TEAEs). Baseline findings are pre-existing and ongoing medical events recorded prior to the start of treatment. Safety data are presented for the safety population by treatment group. Safety was assessed per standard procedures ie, evaluation of AEs, laboratory test results, and vital signs. In addition, viral shedding was assessed in this study. Laboratory/vital sign abnormalities were not to be reported as AEs unless they were considered clinically significant, the abnormality caused study drug dose adjustment or led to the patient’s discontinuation from the study, or if the investigator insisted the abnormality was to be reported as an AE. This study was conducted in 2 parts: a non-randomised Phase 1b safety part and a Phase 2 randomised part.

Primary

All AEs/SAEs that occurred during the course of the study (from the date of informed consent through to the End of Study visit) or 30 days after the last dose of ONCOS-102 or chemotherapy (whichever was administered last) were to be reported.

All AEs were coded for body system and preferred term using MedDRA.

Control Group v Experimental Group

31

Post-hoc

An SAE was defined as any untoward medical occurrence that at any dose: • Resulted in death. • Was immediately life-threatening. • Required inpatient hospitalisation or prolongation of existing hospitalisation. • Resulted in persistent or significant disability/incapacity. • Was a congenital abnormality/birth defect. • Was considered an important medical event ie, may not have been immediately life-threatening or result in death/hospitalisation but may have jeopardised the patient or may have required intervention to prevent one of the other outcomes listed above. In relation to any deaths during the study, as for all other SAEs, these were to be reported if they occurred within the study period or within 30 days of the last dose of ONCOS-102 or pemetrexed/cisplatin/carboplatin (whichever was administered last). All deaths considered unequivocally due to disease progression were not to reported.

Primary

All SAEs that occurred during the course of the study (from the date of informed consent through to the End of Study visit) or 30 days after the last dose of ONCOS-102 or chemotherapy (whichever was administered last) were to be reported.

All SAEs were coded for body system and preferred term using MedDRA.

Experimental Group v Control Group

31

Post-hoc

ORR is summarised by RECIST 1.1 for the ITT population.

Secondary

Overall Response Rate is presented per RECIST 1.1 during the treatment phase. Overall response is defined as Complete Response (CR) or Partial Response (PR) at any time point.

PFS is presented per RECIST 1.1, irRECIST, and PERCIST until the end of the treatment phase. Changes in tumour metabolism and size were evaluated using diagnostic CT imaging and fluorodeoxy-D-glucose PET. The investigator was to make an evaluation of disease status after each PET-CT and CT scan. In the follow-up phase of the study, data regarding disease progression were recorded but not the type of scan. The latest available data for PFS are reported as part of the 21-month follow-up analysis (when all patients had been in the study for at least 21 months). PFS distribution in the Experimental Group versus the Control Group was compared using a log-rank test. The Kaplan-Meier method was applied in the estimation of PFS function.

Secondary

Overall PFS was defined as the time from start of treatment (Day 1) until disease progression or during the follow-up phase regardless of the scan modality or death from any cause.

A log-rank test was applied for OS. If a patient did not reach the endpoint, that patient was censored at the date last known to be alive.

Secondary

OS was determined as the time (weeks and months) from Day 1 until death from any cause.

PFS is presented per RECIST 1.1, irRECIST, and PERCIST until the end of the treatment phase. Changes in tumour metabolism and size were evaluated using diagnostic CT imaging and fluorodeoxy-D-glucose PET. The investigator was to make an evaluation of disease status after each PET-CT and CT scan. In the follow-up phase of the study, data regarding disease progression were recorded but not the type of scan. The latest available data for PFS are reported as part of the 30-month follow-up analysis (when all patients had been in the study for at least 30 months). PFS distribution in the Experimental Group versus the Control Group was compared using a log-rank test. The Kaplan-Meier method was applied in the estimation of PFS function.

Secondary

Overall PFS was defined as the time from start of treatment (Day 1) until disease progression or during the follow-up phase regardless of the scan modality or death from any cause.

A log-rank test was applied for OS. If a patient did not reach the endpoint, that patient was censored at the date last known to be alive.

Secondary

OS was determined as the time (weeks and months) from Day 1 until death from any cause.

All AEs/SAEs were recorded from date of signing of informed consent until up to 30 days after the study treatment. After 30 days, only AEs/SAEs considered related to the study treatment or significant were reported.

Any AEs which were considered unequivocally due to worsening of a patient’s condition, attributable to the disease under study or that occurred after informed consent but before the patient was registered, did not have to be reported as AEs/SAEs.

23.0

Control Group

Experimental Group