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
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Experimental: ONCOS-102+cyclophosphamide+pembrolizumab 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). |
Biological: ONCOS-102
Engineered oncolytic adenovirus expressing Granulocyte-macrophage colony stimulating factor (GM-CSF)
Drug: Cyclophosphamide
Pre-treatment
Drug: Pembrolizumab
PD1 blockade
|
Outcome Measures
Primary Outcome Measures
- Incidence of Treatment-emergent Adverse Events Including Treatment-emergent Serious Adverse Events Assessed by Common Terminology Criteria for Adverse Events (CTCAE). [6 months]
Secondary Outcome Measures
- Objective Response Rates by RECIST 1.1 and irRECIST. [6 months]
- Changes in Immune Cell Subsets in Tumor Tissue Before and After ONCOS-102 and Pembrolizumab. [6 months]
- Changes in Immune Cell Subsets in Peripheral Blood Before and After ONCOS-102 and Pembrolizumab. [6 months]
- Correlation of Tumour Infiltrating Lymphocytes (TILs) and Overall Response Rate (ORR). [6 months]
- Progression Free Survival (PFS) Assessed by RECIST 1.1 and irRECIST. [6 months]
- Clinical Benefit Rate, Defined as Any Confirmed Objective Response by RECIST 1.1 or Stable Disease. [6 months]
- Clinical Benefit Rate, Defined as Any Objective Response by irRECIST Criteria or Immune-related Stable Disease. [6 months]
- Change in Size in Individual Lesions. [6 months]
Other Outcome Measures
- Somatic Mutational Rate and Neoepitope Burden in Tumors and Explore Relationship to Response. [6 months]
- Changes in T Cell Receptor Clonality in Infiltrating and Circulating T Cells. [6 months]
- Gene Expression Changes in the Tumor Microenvironment and Peripheral Blood. [6 months]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
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).
-
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.
Exclusion Criteria:
-
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:
-
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Maryland Comprehensive Cancer Center | Baltimore | Maryland | United States | |
| 2 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | |
| 3 | Fox Chase Cancer Center | Philadelphia | Pennsylvania | United States | |
| 4 | Oslo University Hospital - The Norwegian Radium Hospital | Oslo | Norway |
Sponsors and Collaborators
- Targovax Oy
Investigators
None specified.Study Documents (Full-Text)
More Information
Publications
None provided.- ONCOS C824
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Experimental: ONCOS-102+Cyclophosphamide+Pembrolizumab - Part 1 | Experimental: ONCOS-102+Cyclophosphamide+Pembrolizumab - Part 2 |
|---|---|---|
| Arm/Group Description | 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 receive pembrolizumab i.v., 2mg/kg or 200 mg flat dose on day 22 (Week 3) and every three weeks thereafter until Day 169/Week 24. ONCOS-102: Engineered oncolytic adenovirus expressing Granulocyte-macrophage colony stimulating factor (GM-CSF) Cyclophosphamide: Pre-treatment Pembrolizumab: PD1 blockade | 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). ONCOS-102: Engineered oncolytic adenovirus expressing Granulocyte-macrophage colony stimulating factor (GM-CSF) Cyclophosphamide: Pre-treatment Pembrolizumab: PD1 blockade |
| Period Title: Overall Study | ||
| STARTED | 9 | 12 |
| COMPLETED | 3 | 4 |
| NOT COMPLETED | 6 | 8 |
Baseline Characteristics
| Arm/Group Title | Experimental: ONCOS-102+Cyclophosphamide+Pembrolizumab Part 1 | Experimental: ONCOS-102+Cyclophosphamide+Pembrolizumab Part 2 | Total |
|---|---|---|---|
| Arm/Group Description | 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). ONCOS-102: Engineered oncolytic adenovirus expressing Granulocyte-macrophage colony stimulating factor (GM-CSF) Cyclophosphamide: Pre-treatment Pembrolizumab: PD1 blockade | 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). ONCOS-102: Engineered oncolytic adenovirus expressing Granulocyte-macrophage colony stimulating factor (GM-CSF) Cyclophosphamide: Pre-treatment Pembrolizumab: PD1 blockade | Total of all reporting groups |
| Overall Participants | 9 | 12 | 21 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
2
22.2%
|
6
50%
|
8
38.1%
|
| >=65 years |
7
77.8%
|
6
50%
|
13
61.9%
|
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
69.1
(13.68)
|
67.3
(13.50)
|
68.1
(13.26)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
4
44.4%
|
6
50%
|
10
47.6%
|
| Male |
5
55.6%
|
6
50%
|
11
52.4%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
1
8.3%
|
1
4.8%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
1
11.1%
|
0
0%
|
1
4.8%
|
| White |
8
88.9%
|
11
91.7%
|
19
90.5%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
8
88.9%
|
10
83.3%
|
18
85.7%
|
| Norway |
1
11.1%
|
2
16.7%
|
3
14.3%
|
Outcome Measures
| Title | Incidence of Treatment-emergent Adverse Events Including Treatment-emergent Serious Adverse Events Assessed by Common Terminology Criteria for Adverse Events (CTCAE). |
|---|---|
| Description | |
| Time Frame | 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Experimental: ONCOS-102+Cyclophosphamide+Pembrolizumab Part 1 | Experimental: ONCOS-102+Cyclophosphamide+Pembrolizumab Part 2 |
|---|---|---|
| Arm/Group Description | Part I1 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). ONCOS-102: Engineered oncolytic adenovirus expressing Granulocyte-macrophage colony stimulating factor (GM-CSF) Cyclophosphamide: Pre-treatment Pembrolizumab: PD1 blockade | Part 2: 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). ONCOS-102: Engineered oncolytic adenovirus expressing Granulocyte-macrophage colony stimulating factor (GM-CSF) Cyclophosphamide: Pre-treatment Pembrolizumab: PD1 blockade |
| Measure Participants | 9 | 12 |
| Number of patients with Treatment Emergent Adverse Event (TEAE) |
9
100%
|
12
100%
|
| Number of patients with Treatment Emergent Adverse Serious Event (TESAE) |
4
44.4%
|
2
16.7%
|
| Number of patients with Grade 3 or 4 Treatment Emergent Adverse Event (TEAE) |
5
55.6%
|
4
33.3%
|
| Number of patients with Treatment Emergent Adverse Event related to any of the study treatments |
8
88.9%
|
11
91.7%
|
| Number of patients with fatal events |
0
0%
|
0
0%
|
| Number of patients discontinuing for Adverse Events |
0
0%
|
1
8.3%
|
| Title | Objective Response Rates by RECIST 1.1 and irRECIST. |
|---|---|
| Description | |
| Time Frame | 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Part 1 | Part 2 |
|---|---|---|
| Arm/Group Description | Part 1: 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). ONCOS-102: Engineered oncolytic adenovirus expressing Granulocyte-macrophage colony stimulating factor (GM-CSF) Cyclophosphamide: Pre-treatment Pembrolizumab: PD1 blockade | Part 2: 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). ONCOS-102: Engineered oncolytic adenovirus expressing Granulocyte-macrophage colony stimulating factor (GM-CSF) Cyclophosphamide: Pre-treatment Pembrolizumab: PD1 blockade |
| Measure Participants | 8 | 12 |
| Number of patient with Complete Response or Partial Response |
3
33.3%
|
4
33.3%
|
| Number of patients with Stable Disease or Progressive Disease |
5
55.6%
|
8
66.7%
|
| Title | Changes in Immune Cell Subsets in Tumor Tissue Before and After ONCOS-102 and Pembrolizumab. |
|---|---|
| Description | |
| Time Frame | 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Changes in Immune Cell Subsets in Peripheral Blood Before and After ONCOS-102 and Pembrolizumab. |
|---|---|
| Description | |
| Time Frame | 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Correlation of Tumour Infiltrating Lymphocytes (TILs) and Overall Response Rate (ORR). |
|---|---|
| Description | |
| Time Frame | 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Progression Free Survival (PFS) Assessed by RECIST 1.1 and irRECIST. |
|---|---|
| Description | |
| Time Frame | 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Clinical Benefit Rate, Defined as Any Confirmed Objective Response by RECIST 1.1 or Stable Disease. |
|---|---|
| Description | |
| Time Frame | 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Clinical Benefit Rate, Defined as Any Objective Response by irRECIST Criteria or Immune-related Stable Disease. |
|---|---|
| Description | |
| Time Frame | 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Change in Size in Individual Lesions. |
|---|---|
| Description | |
| Time Frame | 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Somatic Mutational Rate and Neoepitope Burden in Tumors and Explore Relationship to Response. |
|---|---|
| Description | |
| Time Frame | 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Changes in T Cell Receptor Clonality in Infiltrating and Circulating T Cells. |
|---|---|
| Description | |
| Time Frame | 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Gene Expression Changes in the Tumor Microenvironment and Peripheral Blood. |
|---|---|
| Description | |
| Time Frame | 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
Adverse Events
| Time Frame | 27 weeks | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Adverse events were reported according to NCI CTCAE vs 5.0 | |||
| Arm/Group Title | Experimental: ONCOS-102+Cyclophosphamide+Pembrolizumab Part 1 | Experimental: ONCOS-102+Cyclophosphamide+Pembrolizumab Part 2 | ||
| Arm/Group Description | Part 1: 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). ONCOS-102: Engineered oncolytic adenovirus expressing Granulocyte-macrophage colony stimulating factor (GM-CSF) Cyclophosphamide: Pre-treatment Pembrolizumab: PD1 blockade | Part 2: 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). ONCOS-102: Engineered oncolytic adenovirus expressing Granulocyte-macrophage colony stimulating factor (GM-CSF) Cyclophosphamide: Pre-treatment Pembrolizumab: PD1 blockade | ||
All Cause Mortality |
||||
| Experimental: ONCOS-102+Cyclophosphamide+Pembrolizumab Part 1 | Experimental: ONCOS-102+Cyclophosphamide+Pembrolizumab Part 2 | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/9 (0%) | 0/12 (0%) | ||
Serious Adverse Events |
||||
| Experimental: ONCOS-102+Cyclophosphamide+Pembrolizumab Part 1 | Experimental: ONCOS-102+Cyclophosphamide+Pembrolizumab Part 2 | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/9 (44.4%) | 2/12 (16.7%) | ||
| Blood and lymphatic system disorders | ||||
| Haemolytic anaemia | 1/9 (11.1%) | 1 | 0/12 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Abdominal pain | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Diarrhoea | 1/9 (11.1%) | 1 | 0/12 (0%) | 0 |
| Enterocolitis | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| General disorders | ||||
| Non-cardiac chest pain | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Pyrexia | 0/9 (0%) | 0 | 2/12 (16.7%) | 4 |
| Infections and infestations | ||||
| Large intestine infection | 1/9 (11.1%) | 1 | 0/12 (0%) | 0 |
| Pneumonia | 1/9 (11.1%) | 1 | 0/12 (0%) | 0 |
| Staphylococcal infection | 1/9 (11.1%) | 1 | 0/12 (0%) | 0 |
| Investigations | ||||
| Blood bilirubin increased | 1/9 (11.1%) | 1 | 0/12 (0%) | 0 |
| Metabolism and nutrition disorders | ||||
| Diabetic ketoacidosis | 1/9 (11.1%) | 1 | 0/12 (0%) | 0 |
| Hyponatraemia | 1/9 (11.1%) | 1 | 0/12 (0%) | 0 |
| Type 1 diabetes mellitus | 1/9 (11.1%) | 1 | 0/12 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||
| Muscular weakness | 1/9 (11.1%) | 1 | 0/12 (0%) | 0 |
| Nervous system disorders | ||||
| Syncope | 0/9 (0%) | 0 | 1/12 (8.3%) | 2 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Dyspnoea | 0/9 (0%) | 0 | 1/12 (8.3%) | 1 |
| Pneumothorax | 1/9 (11.1%) | 1 | 0/12 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| Experimental: ONCOS-102+Cyclophosphamide+Pembrolizumab Part 1 | Experimental: ONCOS-102+Cyclophosphamide+Pembrolizumab Part 2 | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 9/9 (100%) | 12/12 (100%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 2/9 (22.2%) | 2 | 3/12 (25%) | 4 |
| Gastrointestinal disorders | ||||
| Abdominal distension | 1/9 (11.1%) | 1 | 1/12 (8.3%) | 1 |
| Abdominal pain | 1/9 (11.1%) | 1 | 2/12 (16.7%) | 2 |
| Constipation | 1/9 (11.1%) | 2 | 3/12 (25%) | 3 |
| Diarrhoea | 4/9 (44.4%) | 8 | 1/12 (8.3%) | 1 |
| Nausea | 3/9 (33.3%) | 3 | 4/12 (33.3%) | 9 |
| Vomiting | 2/9 (22.2%) | 2 | 3/12 (25%) | 3 |
| General disorders | ||||
| Chills | 5/9 (55.6%) | 8 | 4/12 (33.3%) | 15 |
| Fatigue | 3/9 (33.3%) | 3 | 3/12 (25%) | 3 |
| Injection site pain | 1/9 (11.1%) | 2 | 3/12 (25%) | 4 |
| Injection site reaction | 0/9 (0%) | 0 | 3/12 (25%) | 3 |
| Malaise | 2/9 (22.2%) | 2 | 0/12 (0%) | 0 |
| Oedema peripheral | 2/9 (22.2%) | 3 | 1/12 (8.3%) | 2 |
| Pain | 0/9 (0%) | 0 | 2/12 (16.7%) | 2 |
| Pyrexia | 3/9 (33.3%) | 7 | 7/12 (58.3%) | 23 |
| Infections and infestations | ||||
| Urinary tract infection | 2/9 (22.2%) | 3 | 1/12 (8.3%) | 1 |
| Investigations | ||||
| Alanine aminotransferase increased | 4/9 (44.4%) | 5 | 3/12 (25%) | 5 |
| Aspartate aminotransferase increased | 2/9 (22.2%) | 8 | 3/12 (25%) | 6 |
| Blood alkaline phosphatase increased | 0/9 (0%) | 0 | 3/12 (25%) | 4 |
| Weight decreased | 1/9 (11.1%) | 1 | 1/12 (8.3%) | 1 |
| White blood cell count decreased | 1/9 (11.1%) | 1 | 1/12 (8.3%) | 4 |
| Blood bilirubin increased | 2/9 (22.2%) | 2 | 0/12 (0%) | 0 |
| Metabolism and nutrition disorders | ||||
| Hypoalbuminaemia | 2/9 (22.2%) | 3 | 2/12 (16.7%) | 3 |
| Hyponatraemia | 1/9 (11.1%) | 2 | 2/12 (16.7%) | 2 |
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 2/9 (22.2%) | 2 | 1/12 (8.3%) | 1 |
| Myalgia | 3/9 (33.3%) | 6 | 0/12 (0%) | 0 |
| Muscular weakness | 2/9 (22.2%) | 2 | 0/12 (0%) | 0 |
| Nervous system disorders | ||||
| Dizziness | 0/9 (0%) | 0 | 2/12 (16.7%) | 2 |
| Headache | 3/9 (33.3%) | 6 | 0/12 (0%) | 0 |
| Renal and urinary disorders | ||||
| Pollakisuria | 1/9 (11.1%) | 1 | 1/12 (8.3%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 1/9 (11.1%) | 1 | 2/12 (16.7%) | 2 |
| Dyspnoea | 1/9 (11.1%) | 2 | 3/12 (25%) | 3 |
| Hiccups | 1/9 (11.1%) | 1 | 1/12 (8.3%) | 1 |
| Nasal congestion | 3/9 (33.3%) | 3 | 0/12 (0%) | 0 |
| Oropharyngeal pain | 1/9 (11.1%) | 1 | 1/12 (8.3%) | 1 |
| Skin and subcutaneous tissue disorders | ||||
| Dermatitis bullous | 0/9 (0%) | 0 | 2/12 (16.7%) | 2 |
| Dry skin | 0/9 (0%) | 0 | 2/12 (16.7%) | 2 |
| Pruritus | 3/9 (33.3%) | 4 | 4/12 (33.3%) | 4 |
| Rash | 2/9 (22.2%) | 3 | 1/12 (8.3%) | 1 |
| Rash maculo-papular | 2/9 (22.2%) | 2 | 3/12 (25%) | 4 |
| Vascular disorders | ||||
| Embolism | 1/9 (11.1%) | 1 | 1/12 (8.3%) | 1 |
| Hypertension | 5/9 (55.6%) | 7 | 4/12 (33.3%) | 5 |
| Hypotension | 0/9 (0%) | 0 | 2/12 (16.7%) | 2 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. Lone H. Ottesen, Chief Development Officer |
|---|---|
| Organization | Targovax |
| Phone | +44 7920567911 |
| lone.ottesen@targovax.com |
- ONCOS C824