Advanced or Unresectable Melanoma Progressing After PD1 BlockadePhase 1NCT03003676

A Pilot Study of Sequential ONCOS-102, an Engineered Oncolytic Adenovirus Expressing GMCSF, and Pembrolizumab in Patients With Advanced or Unresectable Melanoma Progressing After Programmed Cell Death Protein 1 (PD1) Blockade

A Phase 1 study testing ONCOS-102, Cyclophosphamide and Pembrolizumab in people with Advanced or Unresectable Melanoma Progressing After PD1 Blockade, run by Targovax Oy at 4 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Advanced or Unresectable Melanoma Progressing After PD1 Blockade
What is being tested?: ONCOS-102, Cyclophosphamide and Pembrolizumab
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 21 participants
Where: 4 sitesin 2 countries
Study dates: Dec 2016to Oct 2020
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

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

Adults 18 years of age or older.
For US sites: Histopathologically confirmed melanoma with an injectable cutaneous or lymph node metastasis that has progressed in the opinion of the treating investigator despite administering a Food and Drug Administration (FDA) approved anti-PD1 agent, with or without ipilimumab.
For European sites: Histopathologically confirmed melanoma with an injectable cutaneous or lymph node metastasis that has progressed in the opinion of the treating investigator despite administering a regulatory approved anti-PD1 agent, with or without ipilimumab.
Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.
Measurable disease according to RECIST 1.1.
Acceptable coagulation status: international normalised ratio (INR) of blood clotting, prothrombin time and activated partial thromboplastin time within ≤1.5 x upper limit of normal (ULN).

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Completion of local therapy, such as radiation, surgical resection, injectable immunebased therapy, or topical pro-inflammatory agent, 21 days prior to first dose of protocol therapy.
Adverse events from previous cancer therapies (excluding alopecia) must have recovered to grade 1 (CTCAE, most recent version). Stable grade 2 AEs such as endocrine conditions are allowed, and other chronic stable AEs may be considered on a case by case basis by the Principal Investigator.
Clinical stability of brain metastases for at least 4 weeks prior to first day of study therapy.
Acceptable liver and renal functions defined as:
Total bilirubin ≤1.5 x ULN (does not include patients with Gilbert's Disease)
Aspartate aminotransferase (AST, SGOT), alanine aminotransferase (ALT, SGPT) ≤3.0 x ULN
Serum creatinine ≤1.5 x ULN
Acceptable haematological function defined as (Patients can be transfused to meet the haemoglobin entry criteria):
Haemoglobin ≥9 g/dL
Neutrophils ≥1.5 x 10^9/L
Platelet count ≥75 x 10^9/L
Able to provide valid written informed consent.
All women of childbearing potential must have a negative urine or serum pregnancy test at screening.
For US sites: All patients must agree to use barrier contraception (i.e. condom) during study treatment and for 2 months after the last virus treatment and 4 months after the last dose of chemotherapy and pembrolizumab.
For European sites: All patients must agree to use highly effective contraception for at least 6 months (according to the latest country specific SmPC) after administration of CPO, up to 4 months after last dose of pembrolizumab, and up to 2 months after last dose of ONCOS-102, whichever comes last.
For European sites: All women of child-bearing potential must agree to perform pregnancy testing throughout the study starting at baseline, every 3 weeks from day 22 until last dose of study medication (ONCOS-102 and pembrolizumab) and then every month for at least 6 months.

Who cannot join

A concomitant medical condition requiring receipt of a therapeutic anticoagulant that in the opinion of the treating physician cannot safely allow for therapeutic injection of ONCOS-102 and tumor biopsies. Local clinical practice can be followed with regard to holding a therapeutic anticoagulant during invasive procedures such as biopsies.
A concomitant medical condition that in the opinion of the treating physician would pose unreasonable additional risk to therapeutic injection of ONCOS-102.
For US sites: Receipt of Investigational agents within 28 days prior to first dose of protocol therapy.
For European sites: Current participation or participation in a study of an investigational agent within 28 days prior to first dose of protocol therapy. Note: participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
Any symptomatic autoimmune disease (such as lupus, scleroderma, Crohn's disease, ulcerative colitis) that requires administration of >10mg of prednisone equivalent. Lower dose steroids for conditions such as hypophysitis are allowed.
Any prior severe adverse event attributed to prior anti-PD1 therapy that, in the Principal investigator's opinion, would contraindicate pembrolizumab administration such as:

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Grade 2 or higher pneumonitis
Grade 4 AST or ALT elevation
Grade 3 or higher colitis attributable to PD1 blockade; note that colitis attributable to ipilimumab is not excluded
Note: in the absence of clinical symptoms of pancreatitis, elevations of amylase or lipase are not contraindications to therapy on this trial
Known active infection with Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), or HIV. Cleared HBV/HCV infection is not an exclusion, nor is HIV infection with cluster of differentiations 4 (CD4) counts >500 and an undetectable viral load.
Active bacterial, viral, or fungal infections, requiring systemic therapy apart from anti-viral maintenance therapy for HIV.
History of organ transplant.
Patients requiring chronic systemic immunosuppressants, including steroids (prednisone daily equivalent of >10 mg).
Brain metastases that are clinically unstable (e.g. showing unequivocal growth on imaging, requiring radiation therapy, or steroids >10mg of prednisone equivalent) within 4 weeks of first dose of study drug.
Known severe congenital or acquired cellular or humoral immunodeficiency such as common variable immunodeficiency.
For US sites: Women who are pregnant or breast-feeding currently or are planning to conceive during or up to 4 months after end of protocol therapy.
For European sites: Women who are currently pregnant or breast-feeding or are planning to conceive during or up to 6 months after end of protocol therapy.

Trial locations and contacts

4 sites in 2 countries.

Country

City, postcode or hospital

4 sites in 2 countries

United States3 sites

University of Maryland Comprehensive Cancer Center
Baltimore, Maryland
Memorial Sloan Kettering Cancer Center
New York, New York
Fox Chase Cancer Center
Philadelphia, Pennsylvania

Other trials in United States

Norway1 site

Oslo University Hospital - The Norwegian Radium Hospital
Oslo

Other trials in Norway

About this study

Official title: A Pilot Study of Sequential ONCOS-102, an Engineered Oncolytic Adenovirus Expressing GMCSF, and Pembrolizumab in Patients With Advanced or Unresectable Melanoma Progressing After PD1 Blockade

This is a multi center, phase I pilot study of sequential ONCOS-102 and pembrolizumab in patients with advanced or unresectable melanoma progressing after PD1 blockade. The primary objective of the study is to determine the safety of sequential treatment with ONCOS-102 followed by pembrolizumab. The protocol aims to enroll patients into two cohorts: Part I: up to 12 patients will receive sequential treatment with ONCOS-102 followed by pembrolizumab. Part II: up to 12 patients will receive an initial treatment phase with ONCOS-102 followed by a treatment phase with ONCOS-102 in combination with pembrolizumab.

Conditions: Advanced or Unresectable Melanoma Progressing After PD1 Blockade
Being tested: ONCOS-102, Cyclophosphamide, Pembrolizumab

What participants receive

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

ONCOS-102Biological
Engineered oncolytic adenovirus expressing Granulocyte-macrophage colony stimulating factor (GM-CSF)
CyclophosphamideDrug
Pre-treatment
PembrolizumabDrug
PD1 blockade

Study groups in NCT03003676
Study group	Role	What they receive
Experimental: ONCOS-102+cyclophosphamide+pembrolizumab	Experimental	Part I: Patients will receive 3 doses of intratumoral (i.t.) injection of ONCOS-102 (days 1, 4, and 8) at 3x10^11 viral particles (VP), preceded by intravenous (i.v.) cyclophosphamide priming 1-3 days prior to day 1. They will then receive pembrolizumab i.v., 2mg/kg or 200mg flat dose, on day 22 (Week 3) and every 3 weeks thereafter until the end of treatment visit on day 169 (Week 24). Part II: Patients will receive 4 doses of intratumoral (i.t.) injection of ONCOS-102 (days 1, 4, 8 and 15) at 3x10^11 viral particles (VP), preceded by intravenous (i.v.) cyclophosphamide priming 1-3 days prior to day 1. ONCOS-102 will be given in combination with Pembrolizumab starting on Day 22/Week 3 and every three weeks thereafter until Day 169/Week 24 or until unacceptable toxicity or clinically relevant disease progression, whichever occurs first. Pembrolizumab will be given according to institutional practice (2mg/kg or 200mg flat dose). Receives: Biological: ONCOS-102; Drug: Cyclophosphamide; Drug: Pembrolizumab

What is being measured

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

Incidence of Treatment-emergent Adverse Events Including Treatment-emergent Serious Adverse Events Assessed by Common Terminology Criteria for Adverse Events (CTCAE).
Measured: 6 months

Secondary outcomes (8)

Objective Response Rates by RECIST 1.1 and irRECIST.
Measured: 6 months
Changes in Immune Cell Subsets in Tumor Tissue Before and After ONCOS-102 and Pembrolizumab.
Measured: 6 months
Changes in Immune Cell Subsets in Peripheral Blood Before and After ONCOS-102 and Pembrolizumab.
Measured: 6 months
Correlation of Tumour Infiltrating Lymphocytes (TILs) and Overall Response Rate (ORR).
Measured: 6 months
Progression Free Survival (PFS) Assessed by RECIST 1.1 and irRECIST.
Measured: 6 months
Clinical Benefit Rate, Defined as Any Confirmed Objective Response by RECIST 1.1 or Stable Disease.
Measured: 6 months
Clinical Benefit Rate, Defined as Any Objective Response by irRECIST Criteria or Immune-related Stable Disease.
Measured: 6 months
Change in Size in Individual Lesions.
Measured: 6 months

Timeline

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

Dec 2016Oct 2020

First posted28 Dec 2016 (estimated)
Study startDec 2016
Primary completionJul 2020
Study completionOct 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Advanced or Unresectable Melanoma Progressing After PD1 BlockadeStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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: 21 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03003676
Sponsor's protocol ID: ONCOS C824
Status last verified: Jul 2021
First submitted: 19 Dec 2016
Last updated: 8 Nov 2021
Results posted: Yes, on ClinicalTrials.gov

Publications

Kuryk L, Moller AW, Jaderberg M. Combination of immunogenic oncolytic adenovirus ONCOS-102 with anti-PD-1 pembrolizumab exhibits synergistic antitumor effect in humanized A2058 melanoma huNOG mouse model. Oncoimmunology. 2018 Oct 29;8(2):e1532763. doi: 10.1080/2162402X.2018.1532763. eCollection 2019.
PubMed 30713786

Study at a glance

From the registry record, last updated by the sponsor on 8 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Pilot Study of Sequential ONCOS-102, an Engineered Oncolytic Adenovirus Expressing GMCSF, and Pembrolizumab in Patients With Advanced or Unresectable Melanoma Progressing After PD1 Blockade
ClinicalTrials.gov ID: NCT03003676
Acronym / sponsor ID: ONCOS C824
Conditions: Advanced or Unresectable Melanoma Progressing After PD1 Blockade
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 21 participants (actual)
Lead sponsor: Targovax OyIndustry (pharma, biotech, devices)
Study start: Dec 2016
Primary completion: Jul 2020 (actual)
Study completion: Oct 2020 (actual)
First posted: 28 Dec 2016 (estimated)
Results: Posted 9 Aug 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Experimental: ONCOS-102+cyclophosphamide+pembrolizumab	Experimental	Biological: ONCOS-102, Drug: Cyclophosphamide, Drug: PembrolizumabPart I: Patients will receive 3 doses of intratumoral (i.t.) injection of ONCOS-102 (days 1, 4, and 8) at 3x10^11 viral particles (VP), preceded by intravenous (i.v.) cyclophosphamide priming 1-3 days prior to day 1. They will then receive pembrolizumab i.v., 2mg/kg or 200mg flat dose, on day 22 (Week 3) and every 3 weeks thereafter until the end of treatment visit on day 169 (Week 24). Part II: Patients will receive 4 doses of intratumoral (i.t.) injection of ONCOS-102 (days 1, 4, 8 and 15) at 3x10^11 viral particles (VP), preceded by intravenous (i.v.) cyclophosphamide priming 1-3 days prior to day 1. ONCOS-102 will be given in combination with Pembrolizumab starting on Day 22/Week 3 and every three weeks thereafter until Day 169/Week 24 or until unacceptable toxicity or clinically relevant disease progression, whichever occurs first. Pembrolizumab will be given according to institutional practice (2mg/kg or 200mg flat dose).

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (22 listed)

Adults 18 years of age or older.
For US sites: Histopathologically confirmed melanoma with an injectable cutaneous or lymph node metastasis that has progressed in the opinion of the treating investigator despite administering a Food and Drug Administration (FDA) approved anti-PD1 agent, with or without ipilimumab.
For European sites: Histopathologically confirmed melanoma with an injectable cutaneous or lymph node metastasis that has progressed in the opinion of the treating investigator despite administering a regulatory approved anti-PD1 agent, with or without ipilimumab.
Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.
Measurable disease according to RECIST 1.1.

Key exclusion criteria (18 listed)

A concomitant medical condition requiring receipt of a therapeutic anticoagulant that in the opinion of the treating physician cannot safely allow for therapeutic injection of ONCOS-102 and tumor biopsies. Local clinical practice can be followed with regard to holding a therapeutic anticoagulant during invasive procedures such as biopsies.
A concomitant medical condition that in the opinion of the treating physician would pose unreasonable additional risk to therapeutic injection of ONCOS-102.
For US sites: Receipt of Investigational agents within 28 days prior to first dose of protocol therapy.
For European sites: Current participation or participation in a study of an investigational agent within 28 days prior to first dose of protocol therapy. Note: participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
Any symptomatic autoimmune disease (such as lupus, scleroderma, Crohn's disease, ulcerative colitis) that requires administration of >10mg of prednisone equivalent. Lower dose steroids for conditions such as hypophysitis are allowed.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
ONCOS-102Engineered oncolytic adenovirus expressing Granulocyte-macrophage colony stimulating factor (GM-CSF)	Biological	Experimental: ONCOS-102+cyclophosphamide+pembrolizumab
CyclophosphamidePre-treatment	Drug	Experimental: ONCOS-102+cyclophosphamide+pembrolizumab
PembrolizumabPD1 blockade	Drug	Experimental: ONCOS-102+cyclophosphamide+pembrolizumab

Primary outcome

Incidence of Treatment-emergent Adverse Events Including Treatment-emergent Serious Adverse Events Assessed by Common Terminology Criteria for Adverse Events (CTCAE).
Time frame: 6 months

8 secondary outcomes

Objective Response Rates by RECIST 1.1 and irRECIST.
Time frame: 6 months
Changes in Immune Cell Subsets in Tumor Tissue Before and After ONCOS-102 and Pembrolizumab.
Time frame: 6 months
Changes in Immune Cell Subsets in Peripheral Blood Before and After ONCOS-102 and Pembrolizumab.
Time frame: 6 months
Correlation of Tumour Infiltrating Lymphocytes (TILs) and Overall Response Rate (ORR).
Time frame: 6 months
Progression Free Survival (PFS) Assessed by RECIST 1.1 and irRECIST.
Time frame: 6 months
Clinical Benefit Rate, Defined as Any Confirmed Objective Response by RECIST 1.1 or Stable Disease.
Time frame: 6 months
Clinical Benefit Rate, Defined as Any Objective Response by irRECIST Criteria or Immune-related Stable Disease.
Time frame: 6 months
Change in Size in Individual Lesions.
Time frame: 6 months

Results and safety

Results posted to the registry on 9 Aug 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Experimental: ONCOS-102+Cyclophosphamide+Pembrolizumab - Part 1	9	3
Experimental: ONCOS-102+Cyclophosphamide+Pembrolizumab - Part 2	12	4

Primary outcome: Incidence of Treatment-emergent Adverse Events Including Treatment-emergent Serious Adverse Events Assessed by Common Terminology Criteria for Adverse Events (CTCAE).

Time frame: 6 months. Number. Unit: participants

Measure	Experimental: ONCOS-102+Cyclophosphamide+Pembrolizumab Part 1 n = 9	Experimental: ONCOS-102+Cyclophosphamide+Pembrolizumab Part 2 n = 12
Number of patients with Treatment Emergent Adverse Event (TEAE)	9	12
Number of patients with Treatment Emergent Adverse Serious Event (TESAE)	4	2
Number of patients with Grade 3 or 4 Treatment Emergent Adverse Event (TEAE)	5	4
Number of patients with Treatment Emergent Adverse Event related to any of the study treatments	8	11
Number of patients with fatal events	0	0
Number of patients discontinuing for Adverse Events	0	1

8 secondary outcomes are reported in the full results.

Adverse events

Time frame: 27 weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Experimental: ONCOS-102+Cyclophosphamide+Pembrolizumab Part 1	4 of 9 (44.4%)	9 of 9 (100%)	0 of 9
Experimental: ONCOS-102+Cyclophosphamide+Pembrolizumab Part 2	2 of 12 (16.7%)	12 of 12 (100%)	0 of 12

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Nov 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 30713786Kuryk L, Moller AW, Jaderberg M. Combination of immunogenic oncolytic adenovirus ONCOS-102 with anti-PD-1 pembrolizumab exhibits synergistic antitumor effect in humanized A2058 melanoma huNOG mouse model. Oncoimmunology. 2018 Oct 29;8(2):e1532763. doi: 10.1080/2162402X.2018.1532763. eCollection 2019.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

4 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ONCOS-102, Cyclophosphamide and Pembrolizumab in people with Advanced or Unresectable Melanoma Progressing After PD1 Blockade, run by Targovax Oy at 4 sites in 2 countries.

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 22 inclusion and 18 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: finished, as of the sponsor's last update on 8 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States, Norway. 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?

Yes. Results are posted in the registry (first posted 9 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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 Including Treatment-emergent Serious Adverse Events Assessed by Common Terminology Criteria for Adverse Events (CTCAE). (time frame: 6 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 NCT03003676, which also lists 1 linked publication.

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 8 Nov 2021.