Colorectal Cancer, Liver Neoplasms
Conditions
Keywords
Colorectal cancer metastases to liver, Colorectal Cancer, Colorectal Carcinoma, Colorectal Tumors, Colorectal Neoplasms, Rectum Cancer, Rectum tumors, Rectum carcinoma, Colon cancer, Colon tumors, Colon carcinoma, Rectum Neoplasms, Colon Neoplasms, Liver Neoplasms, Hepatic Neoplasms, Liver Tumors, Liver cancer, Hepatic Cancer, Hepatic tumors, metastatic to the liver
Brief summary
This study is an open-label study. It has two stages. Stage 1 is a dose escalation phase of the study to determine and evaluate the safety and tolerability of repeated treatments with a genetically engineered herpes simplex virus NV1020 administered locoregionally to the liver. Stage 2 is to evaluate the dose found in Stage 1 to be optimally tolerated. Stage 2 is to assess the efficacy of the optimally tolerated dose of NV1020 by itself and in combination with second-line chemotherapy. Assignment to Stage 1 or Stage 2 of the study is determined by when the patient enters the study.
Detailed description
This study is designed to evaluate the effects of repeated treatments with NV1020, prior to second-line chemotherapy, and to determine an appropriate dose level of NV1020 in a multiple dose regimen for later Phase II studies. Sequential, open-label cohort dose escalation of NV1020 (stage 1) followed by an expansion of one selected dose cohort (stage 2). Study results will be reviewed periodically by an independent DSMB who will approve each cohort dose escalation. During the dose escalation stage, 3 cohorts of patients (3 in each) will be treated with 4 fixed doses of NV1020, with the dose level increasing for successive cohorts. A patient will be observed for a minimum of 7 days after the first NV1020 infusion before the next patient in the same cohort is given NV1020. The first patient in the next higher dose cohort will receive NV1020 no earlier than 14 days after the last patient in the prior cohort has finished NV1020 infusions. One additional cohort (half log higher increment) may be approved by the DSMB, if considered necessary to define MTD. Dose-limiting toxicity will be determined using NCI CTC criteria and a suitable dose level for later evaluation will be selected. In the second stage of the study, the dose cohort considered to show the best therapeutic index will be expanded by the addition of 18 further patients. For all patients in this study, investigational treatment with NV1020 will be followed by a minimum of two cycles of second-line therapy using anti-neoplastic drugs approved by the FDA for colorectal cancer and selected by the investigator. All patients will be followed up periodically until death. Permission for autopsy will be sought.
Interventions
DRUGNV1020
NV1020 dose levels: 3x10\^6, 1x10\^7, 3x10\^7, and 1x10\^8 plaque forming units, administered via hepatic artery infusion, over 10 minutes and repeated every 1-2 weeks for 4-8 weeks
Sponsors
MediGene
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Ability to understand and willingness to sign a written informed consent (includes willingness to avoid physical intimacy during and for 2 weeks post NV1020 treatment) 2. 18 years or more of age 3. Colorectal adenocarcinoma histologically confirmed within one year prior to enrollment in the study 4. Liver dominant metastases (CT-measurable lesions with less than 50% total liver involvement), histologically confirmed 5. Failed conventional chemotherapy for metastatic disease (e.g. tumors no longer responding to 5-FU/leucovorin in combination with irinotecan or oxaliplatin with or without one monoclonal antibody) 6. Candidate for additional chemotherapy (and/or experimental anti-cancer therapy, if this is the only remaining treatment option) 7. Karnofsky Performance Status 70% or greater 8. Life expectancy greater than or equal to 4 months, based on the investigator's opinion 9. Seropositive for herpes simplex virus-1 (HSV-1) 10. Fecund females: negative for pregnancy test (urine or serum) 11. Effective double-barrier contraception for a minimum of 2 months following final infusion of NV1020
Exclusion criteria
1. Dominant extrahepatic disease, including cerebral metastases, significant malignant ascites or other extrahepatic metastases that are symptomatic, in critical locations or otherwise likely to confound NV1020 evaluations, in the opinion of the investigator 2. Seronegative for HSV-1 3. Significant active/unstable non-malignant disease or laboratory test (hematology and chemistry) results that meet any of the following: * White blood cell count (WBC) less than or equal to 3 x 10e3/mm3 * Absolute neutrophil count (ANC) less than or equal to 1.5 x 10e3/mm3 * Platelets less than or equal to 100,000/mm3 * Hemoglobin (Hgb) less than or equal to 9.0 g/dL * Prothrombin time/partial thromboplastin time (PT/PTT) \> upper limit of normal (ULN) * Serum creatinine \> 2.0 mg/dL * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 2.5 times ULN or total bilirubin \> 1.5 times ULN * Alkaline phosphatase \> 2.5 times ULN 4. Chemotherapy \< 4 weeks prior to the first NV1020 infusion (mitomycin or nitrosurea \< 6 weeks) 5. Immunotherapy \< 6 weeks prior to the first NV1020 infusion 6. Radiotherapy (external or internal) to the liver 7. Major surgery (excluding pump placement and cholecystectomy) ≤ 2 weeks prior to the first NV1020 infusion but the subject must be clinically stable. Pump placement and cholecystectomy ≤ 1 week prior to the first NV1020 infusion but the subject must be clinically stable 8. Female who is pregnant or nursing 9. Patients wishing to conceive within 2 months after the last infusion of NV1020 10. Any investigational agent administered less than or equal to 4 weeks prior to NV1020 infusion 11. Acute HSV infection requiring systemic antiviral therapy or history of serious HSV infection (e.g., ocular, encephalitic, etc.) 12. Active viral hepatitis (evidence for infection with hepatitis A, B or C viruses) 13. Known infection with HIV 14. Known hypersensitivity to any component of the NV1020 formulation 15. History of, or current, bleeding or coagulation disorder 16. History of significant hepatic fibrosis, cirrhosis, or hemachromatosis 17. History of malignancy other than colorectal cancer, within 5 years prior to start of study participation, with the exception of in situ cervical or skin carcinoma 18. Active severe infection and any other concurrent disease or medical conditions that are likely to interfere with the study, as judged by the investigator 19. Systemic corticosteroid administration \< 4 weeks prior to starting NV1020 treatment 20. Prior treatment with NV1020 or other putative oncolytic viruses
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events and Dose Limiting Adverse Events | From start of treatment through 12 months after completion of treatment | Incidence of adverse events for all patients (N=32); Overall incidence ≥20%; Adverse events listed by Medical Dictionary for Regulatory Activities (MedDRA) Preferred Term |
| NV1020 Pharmacokinetics - Presence of NV1020 in Body Fluids/Skin | Daily for 2 weeks after the first and last NV1020 infusions | Number of patients with NV1020 detected in saliva, skin, and/or mucosal surfaces; Analysis by polymerase chain reaction (PCR) |
| Clinical Laboratory Safety - Hematology | Screening; after each NV1020 infusion; +7h, +24h, and +72h after NV1020 infusion; each chemotherapy visit; +3d, +7d, +14d after each chemo visit; 1 week after end of treatment | Number of patients with clinically significant hematology laboratory abnormalities by NV1020 dose cohort (Post baseline) |
| Clinical Laboratory Safety - Chemistry | Screening; after each NV1020 infusion; +7h, +24h, and +72h after NV1020 infusion; each chemotherapy visit; +3d, +7d, +14d after each chemo visit; 1 week after end of treatment | Number of patients with post-baseline clinically significant laboratory chemistry abnormalities by NV1020 dose cohort |
| Clinical Laboratory Safety - Coagulation | Screening; after each NV1020 infusion; +7h, +24h, and +72h after NV1020 infusion; each chemotherapy visit; +3d, +7d, +14d after each chemo visit; 1 week after end of treatment | Number of patients with post-baseline clinically significant laboratory coagulation abnormalities by NV1020 dose cohort |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacodynamic Effects of NV1020: Serum Cytokines (IL-6) | Baseline, after each NV1020 infusion (Visit 1, Visit 3, Visit 5, Visit 7) | Median change from baseline of Interleukin-6 (IL-6) 8 hours post NV1020 infusion (Visits 1, 3, 5, 7) |
| Mean Change From Baseline in Serum Carcinoembryonic Antigen (CEA) After Administration of NV1020 and 2 Cycles of Chemotherapy | Screening (baseline), Chemo visit 1, Chemo visit 2, Follow-up Visit 1 (1 week after end of treatment), Follow-up Visit 2 (+6M), Follow-up Visit 3 (+9M), Follow-up Visit 4 (+12M) | — |
| Pharmacodynamic Effects of NV1020: Serum Cytokines (TNF-alpha) | Baseline, after each NV1020 infusion (Visit 1, Visit 3, Visit 5, Visit 7) | Median change from baseline of tumor necrosis factor (TNF-alpha) 8 hours post NV1020 infusion (Visits 1, 3, 5, 7) |
| Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Screening (baseline), Chemo visit 1, Follow-up visits 1 (1 week post end of treatment), 2 (+6M), 3 (+9M), 4 (+12M) | Maximum percentage changes in tumor diameter after administration of NV1020 followed by chemotherapy as measured by CT scan and Modified Response Evaluation Criteria in Solid Tumors (RECIST) assessment |
| Pharmacodynamic Effects of NV1020: NV1020 Neutralizing Antibody Titer Assay | Screening, Chemo Visit 1, Follow-up Visits 1 (1 week post end of treatment), 2 (+6M), 3 (+9M), 4 (+12M) | Mean change from baseline in NV1020 neutralizing antibody titer by dose cohort |
| Time to Disease Progression; Survival Time | Progression: Chemo visit 1, FU1 (1 week post treatment), FU2 (+6M), FU3 (+9M), FU4 (+12M); Survival: death of patient | Progression assessed from CT and PET measurements and is determined as an increase of greater than or equal to 25% in the sum of the products of perpendicular diameters of all tumors, or the appearance of any new lesion. |
| Pharmacodynamic Effects of NV1020: Serum Cytokines (INF Gamma) | Baseline, after each NV1020 infusion (Visit 1, Visit 3, Visit 5, Visit 7) | Median change from baseline of Interferon (INF) gamma 8 hours post NV1020 infusion (Visits 1, 3, 5, 7) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| NV1020 Escalating doses of NV1020: 3x10\^6, 1x10\^7, 3x10\^7, 1x10\^8 | 32 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 15 |
| Overall Study | other treatment | 5 |
| Overall Study | Subject noncompliance | 2 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | NV1020 |
|---|---|
| Age, Continuous | 57.7 years STANDARD_DEVIATION 11.9 |
| Carcinoembryonic Antigen (CEA) Level at Screening | 175.5 ng/mL STANDARD_DEVIATION 517.4 |
| Karnofsky Performance Status (KPS) KPS 100 | 14 participants |
| Karnofsky Performance Status (KPS) KPS 80 | 1 participants |
| Karnofsky Performance Status (KPS) KPS 90 | 17 participants |
| Prior Chemotherapy | 32 participants |
| Race/Ethnicity, Customized African American | 1 participants |
| Race/Ethnicity, Customized Asian | 1 participants |
| Race/Ethnicity, Customized Caucasian | 29 participants |
| Race/Ethnicity, Customized Hispanic | 1 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 32 / 32 |
| serious Total, serious adverse events | 5 / 32 |
Outcome results
Primary
Clinical Laboratory Safety - Chemistry
Number of patients with post-baseline clinically significant laboratory chemistry abnormalities by NV1020 dose cohort
Time frame: Screening; after each NV1020 infusion; +7h, +24h, and +72h after NV1020 infusion; each chemotherapy visit; +3d, +7d, +14d after each chemo visit; 1 week after end of treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Patients | Clinical Laboratory Safety - Chemistry | Alkaline Phosphatase (U/L) | 2 participants |
| All Patients | Clinical Laboratory Safety - Chemistry | ALT (SGPT) (U/L) | 0 participants |
| All Patients | Clinical Laboratory Safety - Chemistry | AST (SGOT) (U/L) | 1 participants |
| All Patients | Clinical Laboratory Safety - Chemistry | Bicarbonate (mmol/L) | 0 participants |
| All Patients | Clinical Laboratory Safety - Chemistry | BUN (mg/dL) | 0 participants |
| All Patients | Clinical Laboratory Safety - Chemistry | Calcium (mg/dL) | 0 participants |
| All Patients | Clinical Laboratory Safety - Chemistry | Chloride (mmol/L) | 0 participants |
| All Patients | Clinical Laboratory Safety - Chemistry | Creatinine (mg/dL) | 1 participants |
| All Patients | Clinical Laboratory Safety - Chemistry | Glucose (mg/dL) | 1 participants |
| All Patients | Clinical Laboratory Safety - Chemistry | Potassium (mmol/L) | 0 participants |
| All Patients | Clinical Laboratory Safety - Chemistry | Sodium (mmol/L) | 0 participants |
| All Patients | Clinical Laboratory Safety - Chemistry | Total Bilirubin (mg/dL) | 1 participants |
| All Patients | Clinical Laboratory Safety - Chemistry | YGT/GGT (U/L) | 2 participants |
| Dose Cohort 2 | Clinical Laboratory Safety - Chemistry | Bicarbonate (mmol/L) | 0 participants |
| Dose Cohort 2 | Clinical Laboratory Safety - Chemistry | YGT/GGT (U/L) | 2 participants |
| Dose Cohort 2 | Clinical Laboratory Safety - Chemistry | Sodium (mmol/L) | 0 participants |
| Dose Cohort 2 | Clinical Laboratory Safety - Chemistry | Creatinine (mg/dL) | 1 participants |
| Dose Cohort 2 | Clinical Laboratory Safety - Chemistry | AST (SGOT) (U/L) | 0 participants |
| Dose Cohort 2 | Clinical Laboratory Safety - Chemistry | Alkaline Phosphatase (U/L) | 2 participants |
| Dose Cohort 2 | Clinical Laboratory Safety - Chemistry | Potassium (mmol/L) | 1 participants |
| Dose Cohort 2 | Clinical Laboratory Safety - Chemistry | Glucose (mg/dL) | 1 participants |
| Dose Cohort 2 | Clinical Laboratory Safety - Chemistry | Calcium (mg/dL) | 0 participants |
| Dose Cohort 2 | Clinical Laboratory Safety - Chemistry | BUN (mg/dL) | 1 participants |
| Dose Cohort 2 | Clinical Laboratory Safety - Chemistry | ALT (SGPT) (U/L) | 0 participants |
| Dose Cohort 2 | Clinical Laboratory Safety - Chemistry | Total Bilirubin (mg/dL) | 0 participants |
| Dose Cohort 2 | Clinical Laboratory Safety - Chemistry | Chloride (mmol/L) | 0 participants |
| Dose Cohort 3 | Clinical Laboratory Safety - Chemistry | Sodium (mmol/L) | 0 participants |
| Dose Cohort 3 | Clinical Laboratory Safety - Chemistry | Bicarbonate (mmol/L) | 0 participants |
| Dose Cohort 3 | Clinical Laboratory Safety - Chemistry | BUN (mg/dL) | 0 participants |
| Dose Cohort 3 | Clinical Laboratory Safety - Chemistry | YGT/GGT (U/L) | 0 participants |
| Dose Cohort 3 | Clinical Laboratory Safety - Chemistry | Calcium (mg/dL) | 0 participants |
| Dose Cohort 3 | Clinical Laboratory Safety - Chemistry | Chloride (mmol/L) | 0 participants |
| Dose Cohort 3 | Clinical Laboratory Safety - Chemistry | Total Bilirubin (mg/dL) | 0 participants |
| Dose Cohort 3 | Clinical Laboratory Safety - Chemistry | Creatinine (mg/dL) | 0 participants |
| Dose Cohort 3 | Clinical Laboratory Safety - Chemistry | Glucose (mg/dL) | 0 participants |
| Dose Cohort 3 | Clinical Laboratory Safety - Chemistry | Potassium (mmol/L) | 0 participants |
| Dose Cohort 3 | Clinical Laboratory Safety - Chemistry | Alkaline Phosphatase (U/L) | 0 participants |
| Dose Cohort 3 | Clinical Laboratory Safety - Chemistry | ALT (SGPT) (U/L) | 0 participants |
| Dose Cohort 3 | Clinical Laboratory Safety - Chemistry | AST (SGOT) (U/L) | 0 participants |
| Dose Cohort 4 | Clinical Laboratory Safety - Chemistry | Potassium (mmol/L) | 4 participants |
| Dose Cohort 4 | Clinical Laboratory Safety - Chemistry | Creatinine (mg/dL) | 0 participants |
| Dose Cohort 4 | Clinical Laboratory Safety - Chemistry | Bicarbonate (mmol/L) | 1 participants |
| Dose Cohort 4 | Clinical Laboratory Safety - Chemistry | Alkaline Phosphatase (U/L) | 8 participants |
| Dose Cohort 4 | Clinical Laboratory Safety - Chemistry | Chloride (mmol/L) | 1 participants |
| Dose Cohort 4 | Clinical Laboratory Safety - Chemistry | Calcium (mg/dL) | 0 participants |
| Dose Cohort 4 | Clinical Laboratory Safety - Chemistry | AST (SGOT) (U/L) | 6 participants |
| Dose Cohort 4 | Clinical Laboratory Safety - Chemistry | ALT (SGPT) (U/L) | 6 participants |
| Dose Cohort 4 | Clinical Laboratory Safety - Chemistry | BUN (mg/dL) | 0 participants |
| Dose Cohort 4 | Clinical Laboratory Safety - Chemistry | Glucose (mg/dL) | 0 participants |
| Dose Cohort 4 | Clinical Laboratory Safety - Chemistry | YGT/GGT (U/L) | 5 participants |
| Dose Cohort 4 | Clinical Laboratory Safety - Chemistry | Total Bilirubin (mg/dL) | 5 participants |
| Dose Cohort 4 | Clinical Laboratory Safety - Chemistry | Sodium (mmol/L) | 0 participants |
Primary
Clinical Laboratory Safety - Coagulation
Number of patients with post-baseline clinically significant laboratory coagulation abnormalities by NV1020 dose cohort
Time frame: Screening; after each NV1020 infusion; +7h, +24h, and +72h after NV1020 infusion; each chemotherapy visit; +3d, +7d, +14d after each chemo visit; 1 week after end of treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Patients | Clinical Laboratory Safety - Coagulation | C-reactive Protein (mg/dL) | 1 participants |
| All Patients | Clinical Laboratory Safety - Coagulation | D-dimer (ug/mL) | 2 participants |
| All Patients | Clinical Laboratory Safety - Coagulation | Fibrinogen (ug/mL) | 2 participants |
| All Patients | Clinical Laboratory Safety - Coagulation | INR | 0 participants |
| All Patients | Clinical Laboratory Safety - Coagulation | Prothrombin Time (PT) (sec) | 0 participants |
| All Patients | Clinical Laboratory Safety - Coagulation | Partial Thromboplastin Time (PTT) (sec) | 1 participants |
| Dose Cohort 2 | Clinical Laboratory Safety - Coagulation | Partial Thromboplastin Time (PTT) (sec) | 0 participants |
| Dose Cohort 2 | Clinical Laboratory Safety - Coagulation | INR | 0 participants |
| Dose Cohort 2 | Clinical Laboratory Safety - Coagulation | C-reactive Protein (mg/dL) | 1 participants |
| Dose Cohort 2 | Clinical Laboratory Safety - Coagulation | Fibrinogen (ug/mL) | 0 participants |
| Dose Cohort 2 | Clinical Laboratory Safety - Coagulation | D-dimer (ug/mL) | 1 participants |
| Dose Cohort 2 | Clinical Laboratory Safety - Coagulation | Prothrombin Time (PT) (sec) | 0 participants |
| Dose Cohort 3 | Clinical Laboratory Safety - Coagulation | D-dimer (ug/mL) | 0 participants |
| Dose Cohort 3 | Clinical Laboratory Safety - Coagulation | Fibrinogen (ug/mL) | 0 participants |
| Dose Cohort 3 | Clinical Laboratory Safety - Coagulation | INR | 0 participants |
| Dose Cohort 3 | Clinical Laboratory Safety - Coagulation | Partial Thromboplastin Time (PTT) (sec) | 0 participants |
| Dose Cohort 3 | Clinical Laboratory Safety - Coagulation | Prothrombin Time (PT) (sec) | 0 participants |
| Dose Cohort 3 | Clinical Laboratory Safety - Coagulation | C-reactive Protein (mg/dL) | 0 participants |
| Dose Cohort 4 | Clinical Laboratory Safety - Coagulation | Prothrombin Time (PT) (sec) | 3 participants |
| Dose Cohort 4 | Clinical Laboratory Safety - Coagulation | Partial Thromboplastin Time (PTT) (sec) | 3 participants |
| Dose Cohort 4 | Clinical Laboratory Safety - Coagulation | D-dimer (ug/mL) | 6 participants |
| Dose Cohort 4 | Clinical Laboratory Safety - Coagulation | INR | 0 participants |
| Dose Cohort 4 | Clinical Laboratory Safety - Coagulation | C-reactive Protein (mg/dL) | 6 participants |
| Dose Cohort 4 | Clinical Laboratory Safety - Coagulation | Fibrinogen (ug/mL) | 4 participants |
Primary
Clinical Laboratory Safety - Hematology
Number of patients with clinically significant hematology laboratory abnormalities by NV1020 dose cohort (Post baseline)
Time frame: Screening; after each NV1020 infusion; +7h, +24h, and +72h after NV1020 infusion; each chemotherapy visit; +3d, +7d, +14d after each chemo visit; 1 week after end of treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Patients | Clinical Laboratory Safety - Hematology | Monocytes (%) | 1 participants |
| All Patients | Clinical Laboratory Safety - Hematology | Platelets (x10^3/uL) | 0 participants |
| All Patients | Clinical Laboratory Safety - Hematology | Neutrophils (bands) (%) | 1 participants |
| All Patients | Clinical Laboratory Safety - Hematology | Neutrophils (segs) (%) | 1 participants |
| All Patients | Clinical Laboratory Safety - Hematology | White blood cells (x10^3/uL) | 1 participants |
| All Patients | Clinical Laboratory Safety - Hematology | Eosinophils (%) | 0 participants |
| All Patients | Clinical Laboratory Safety - Hematology | Absolute neutrophil count (x10^3/uL) | 1 participants |
| All Patients | Clinical Laboratory Safety - Hematology | Hematocrit (%) | 0 participants |
| All Patients | Clinical Laboratory Safety - Hematology | Hemoglobin (g/dL) | 0 participants |
| All Patients | Clinical Laboratory Safety - Hematology | Basophils (%) | 0 participants |
| All Patients | Clinical Laboratory Safety - Hematology | Red blood cells (x10^6/uL) | 0 participants |
| All Patients | Clinical Laboratory Safety - Hematology | Lymphocytes (%) | 1 participants |
| Dose Cohort 2 | Clinical Laboratory Safety - Hematology | Basophils (%) | 0 participants |
| Dose Cohort 2 | Clinical Laboratory Safety - Hematology | Monocytes (%) | 1 participants |
| Dose Cohort 2 | Clinical Laboratory Safety - Hematology | Absolute neutrophil count (x10^3/uL) | 0 participants |
| Dose Cohort 2 | Clinical Laboratory Safety - Hematology | Hematocrit (%) | 1 participants |
| Dose Cohort 2 | Clinical Laboratory Safety - Hematology | White blood cells (x10^3/uL) | 0 participants |
| Dose Cohort 2 | Clinical Laboratory Safety - Hematology | Neutrophils (bands) (%) | 0 participants |
| Dose Cohort 2 | Clinical Laboratory Safety - Hematology | Neutrophils (segs) (%) | 0 participants |
| Dose Cohort 2 | Clinical Laboratory Safety - Hematology | Red blood cells (x10^6/uL) | 0 participants |
| Dose Cohort 2 | Clinical Laboratory Safety - Hematology | Platelets (x10^3/uL) | 0 participants |
| Dose Cohort 2 | Clinical Laboratory Safety - Hematology | Hemoglobin (g/dL) | 1 participants |
| Dose Cohort 2 | Clinical Laboratory Safety - Hematology | Eosinophils (%) | 0 participants |
| Dose Cohort 2 | Clinical Laboratory Safety - Hematology | Lymphocytes (%) | 0 participants |
| Dose Cohort 3 | Clinical Laboratory Safety - Hematology | Neutrophils (bands) (%) | 0 participants |
| Dose Cohort 3 | Clinical Laboratory Safety - Hematology | Absolute neutrophil count (x10^3/uL) | 0 participants |
| Dose Cohort 3 | Clinical Laboratory Safety - Hematology | Basophils (%) | 0 participants |
| Dose Cohort 3 | Clinical Laboratory Safety - Hematology | Eosinophils (%) | 0 participants |
| Dose Cohort 3 | Clinical Laboratory Safety - Hematology | Hematocrit (%) | 0 participants |
| Dose Cohort 3 | Clinical Laboratory Safety - Hematology | Hemoglobin (g/dL) | 0 participants |
| Dose Cohort 3 | Clinical Laboratory Safety - Hematology | Lymphocytes (%) | 0 participants |
| Dose Cohort 3 | Clinical Laboratory Safety - Hematology | Monocytes (%) | 0 participants |
| Dose Cohort 3 | Clinical Laboratory Safety - Hematology | Neutrophils (segs) (%) | 0 participants |
| Dose Cohort 3 | Clinical Laboratory Safety - Hematology | Platelets (x10^3/uL) | 0 participants |
| Dose Cohort 3 | Clinical Laboratory Safety - Hematology | Red blood cells (x10^6/uL) | 0 participants |
| Dose Cohort 3 | Clinical Laboratory Safety - Hematology | White blood cells (x10^3/uL) | 0 participants |
| Dose Cohort 4 | Clinical Laboratory Safety - Hematology | Monocytes (%) | 1 participants |
| Dose Cohort 4 | Clinical Laboratory Safety - Hematology | Lymphocytes (%) | 1 participants |
| Dose Cohort 4 | Clinical Laboratory Safety - Hematology | Absolute neutrophil count (x10^3/uL) | 0 participants |
| Dose Cohort 4 | Clinical Laboratory Safety - Hematology | Platelets (x10^3/uL) | 3 participants |
| Dose Cohort 4 | Clinical Laboratory Safety - Hematology | Hemoglobin (g/dL) | 3 participants |
| Dose Cohort 4 | Clinical Laboratory Safety - Hematology | Hematocrit (%) | 3 participants |
| Dose Cohort 4 | Clinical Laboratory Safety - Hematology | White blood cells (x10^3/uL) | 7 participants |
| Dose Cohort 4 | Clinical Laboratory Safety - Hematology | Red blood cells (x10^6/uL) | 1 participants |
| Dose Cohort 4 | Clinical Laboratory Safety - Hematology | Neutrophils (bands) (%) | 0 participants |
| Dose Cohort 4 | Clinical Laboratory Safety - Hematology | Eosinophils (%) | 2 participants |
| Dose Cohort 4 | Clinical Laboratory Safety - Hematology | Basophils (%) | 1 participants |
| Dose Cohort 4 | Clinical Laboratory Safety - Hematology | Neutrophils (segs) (%) | 2 participants |
Primary
Incidence of Adverse Events and Dose Limiting Adverse Events
Incidence of adverse events for all patients (N=32); Overall incidence ≥20%; Adverse events listed by Medical Dictionary for Regulatory Activities (MedDRA) Preferred Term
Time frame: From start of treatment through 12 months after completion of treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Patients | Incidence of Adverse Events and Dose Limiting Adverse Events | Dose limiting adverse events | 0 percentage of participants |
| All Patients | Incidence of Adverse Events and Dose Limiting Adverse Events | Nausea | 69 percentage of participants |
| All Patients | Incidence of Adverse Events and Dose Limiting Adverse Events | Abdominal pain | 47 percentage of participants |
| All Patients | Incidence of Adverse Events and Dose Limiting Adverse Events | Diarrhea | 44 percentage of participants |
| All Patients | Incidence of Adverse Events and Dose Limiting Adverse Events | Vomiting | 41 percentage of participants |
| All Patients | Incidence of Adverse Events and Dose Limiting Adverse Events | Abdominal pain upper | 25 percentage of participants |
| All Patients | Incidence of Adverse Events and Dose Limiting Adverse Events | Constipation | 22 percentage of participants |
| All Patients | Incidence of Adverse Events and Dose Limiting Adverse Events | Pyrexia | 94 percentage of participants |
| All Patients | Incidence of Adverse Events and Dose Limiting Adverse Events | Chills | 56 percentage of participants |
| All Patients | Incidence of Adverse Events and Dose Limiting Adverse Events | Fatigue | 56 percentage of participants |
| All Patients | Incidence of Adverse Events and Dose Limiting Adverse Events | Edema peripheral | 22 percentage of participants |
| All Patients | Incidence of Adverse Events and Dose Limiting Adverse Events | Back pain | 34 percentage of participants |
| All Patients | Incidence of Adverse Events and Dose Limiting Adverse Events | Headache | 41 percentage of participants |
| All Patients | Incidence of Adverse Events and Dose Limiting Adverse Events | Anemia | 41 percentage of participants |
| All Patients | Incidence of Adverse Events and Dose Limiting Adverse Events | Neutropenia | 22 percentage of participants |
| All Patients | Incidence of Adverse Events and Dose Limiting Adverse Events | Rash | 28 percentage of participants |
| All Patients | Incidence of Adverse Events and Dose Limiting Adverse Events | Hypokalemia | 22 percentage of participants |
| All Patients | Incidence of Adverse Events and Dose Limiting Adverse Events | Insomnia | 22 percentage of participants |
Primary
NV1020 Pharmacokinetics - Presence of NV1020 in Body Fluids/Skin
Number of patients with NV1020 detected in saliva, skin, and/or mucosal surfaces; Analysis by polymerase chain reaction (PCR)
Time frame: Daily for 2 weeks after the first and last NV1020 infusions
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Patients | NV1020 Pharmacokinetics - Presence of NV1020 in Body Fluids/Skin | 0 participants |
Secondary
Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment
Maximum percentage changes in tumor diameter after administration of NV1020 followed by chemotherapy as measured by CT scan and Modified Response Evaluation Criteria in Solid Tumors (RECIST) assessment
Time frame: Screening (baseline), Chemo visit 1, Follow-up visits 1 (1 week post end of treatment), 2 (+6M), 3 (+9M), 4 (+12M)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Patients | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 804 | NA percentage |
| All Patients | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 303 | 10.74 percentage |
| All Patients | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 805 | NA percentage |
| All Patients | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 202 | 21.55 percentage |
| All Patients | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 806 | NA percentage |
| All Patients | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 103 | 18.85 percentage |
| All Patients | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 807 | NA percentage |
| All Patients | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 401 | -24.51 percentage |
| All Patients | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 808 | NA percentage |
| All Patients | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 203 | 25.00 percentage |
| All Patients | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 809 | NA percentage |
| All Patients | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 402 | -5.36 percentage |
| All Patients | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 810 | NA percentage |
| All Patients | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 102 | 41.76 percentage |
| All Patients | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 811 | NA percentage |
| All Patients | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 403 | -7.98 percentage |
| All Patients | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 812 | NA percentage |
| All Patients | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 301 | 4.92 percentage |
| All Patients | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 813 | NA percentage |
| All Patients | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 801 | NA percentage |
| All Patients | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 814 | NA percentage |
| All Patients | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 201 | 36.91 percentage |
| All Patients | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 815 | NA percentage |
| All Patients | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 802 | NA percentage |
| All Patients | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 816 | NA percentage |
| All Patients | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 302 | 24.55 percentage |
| All Patients | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 817 | NA percentage |
| All Patients | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 803 | NA percentage |
| All Patients | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 818 | NA percentage |
| All Patients | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 101 | 22.70 percentage |
| All Patients | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 819 | NA percentage |
| All Patients | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 304 | 2.68 percentage |
| Dose Cohort 2 | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 819 | -24.18 percentage |
| Dose Cohort 2 | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 101 | NA percentage |
| Dose Cohort 2 | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 102 | NA percentage |
| Dose Cohort 2 | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 103 | NA percentage |
| Dose Cohort 2 | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 201 | NA percentage |
| Dose Cohort 2 | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 202 | NA percentage |
| Dose Cohort 2 | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 203 | NA percentage |
| Dose Cohort 2 | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 301 | NA percentage |
| Dose Cohort 2 | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 302 | NA percentage |
| Dose Cohort 2 | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 303 | NA percentage |
| Dose Cohort 2 | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 304 | NA percentage |
| Dose Cohort 2 | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 401 | NA percentage |
| Dose Cohort 2 | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 402 | NA percentage |
| Dose Cohort 2 | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 403 | NA percentage |
| Dose Cohort 2 | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 801 | 5.45 percentage |
| Dose Cohort 2 | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 802 | 35.89 percentage |
| Dose Cohort 2 | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 803 | -35.56 percentage |
| Dose Cohort 2 | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 804 | 21.43 percentage |
| Dose Cohort 2 | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 805 | 11.41 percentage |
| Dose Cohort 2 | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 806 | 18.90 percentage |
| Dose Cohort 2 | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 807 | 29.98 percentage |
| Dose Cohort 2 | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 808 | 16.77 percentage |
| Dose Cohort 2 | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 809 | 30.00 percentage |
| Dose Cohort 2 | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 810 | 57.67 percentage |
| Dose Cohort 2 | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 811 | -1.93 percentage |
| Dose Cohort 2 | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 812 | -19.05 percentage |
| Dose Cohort 2 | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 813 | 25.29 percentage |
| Dose Cohort 2 | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 814 | 114.29 percentage |
| Dose Cohort 2 | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 815 | 9.38 percentage |
| Dose Cohort 2 | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 816 | 12.20 percentage |
| Dose Cohort 2 | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 817 | 3.30 percentage |
| Dose Cohort 2 | Liver Tumor Response After Administration of NV1020 Followed by Chemotherapy, Determined by Radiological (Computed Tomography [CT] Scan) Assessment | Patient 818 | -11.19 percentage |
Secondary
Mean Change From Baseline in Serum Carcinoembryonic Antigen (CEA) After Administration of NV1020 and 2 Cycles of Chemotherapy
Time frame: Screening (baseline), Chemo visit 1, Chemo visit 2, Follow-up Visit 1 (1 week after end of treatment), Follow-up Visit 2 (+6M), Follow-up Visit 3 (+9M), Follow-up Visit 4 (+12M)
Population: Number of participants analyzed decreases through the follow-up visits. Thus the Number of Participants Analyzed indicated here refer to the number at baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Patients | Mean Change From Baseline in Serum Carcinoembryonic Antigen (CEA) After Administration of NV1020 and 2 Cycles of Chemotherapy | Mean Change - Follow-up 3 | NA ng/mL | — |
| All Patients | Mean Change From Baseline in Serum Carcinoembryonic Antigen (CEA) After Administration of NV1020 and 2 Cycles of Chemotherapy | Mean Change - Follow-up 4 | NA ng/mL | — |
| All Patients | Mean Change From Baseline in Serum Carcinoembryonic Antigen (CEA) After Administration of NV1020 and 2 Cycles of Chemotherapy | Mean Change - Chemo visit 2 | 17.9 ng/mL | Standard Deviation 13.2 |
| All Patients | Mean Change From Baseline in Serum Carcinoembryonic Antigen (CEA) After Administration of NV1020 and 2 Cycles of Chemotherapy | Mean Change - Chemo visit 1 | 869.6 ng/mL | Standard Deviation 1489.9 |
| All Patients | Mean Change From Baseline in Serum Carcinoembryonic Antigen (CEA) After Administration of NV1020 and 2 Cycles of Chemotherapy | Mean Baseline CEA | 1814.4 ng/mL | Standard Deviation 3105.2 |
| All Patients | Mean Change From Baseline in Serum Carcinoembryonic Antigen (CEA) After Administration of NV1020 and 2 Cycles of Chemotherapy | Mean Change - Follow-up 2 | 6995.9 ng/mL | Standard Deviation 12110.6 |
| All Patients | Mean Change From Baseline in Serum Carcinoembryonic Antigen (CEA) After Administration of NV1020 and 2 Cycles of Chemotherapy | Mean Change - Follow-up 1 | -353.9 ng/mL | Standard Deviation 628.8 |
| Dose Cohort 2 | Mean Change From Baseline in Serum Carcinoembryonic Antigen (CEA) After Administration of NV1020 and 2 Cycles of Chemotherapy | Mean Baseline CEA | 161.0 ng/mL | Standard Deviation 235.1 |
| Dose Cohort 2 | Mean Change From Baseline in Serum Carcinoembryonic Antigen (CEA) After Administration of NV1020 and 2 Cycles of Chemotherapy | Mean Change - Follow-up 4 | NA ng/mL | — |
| Dose Cohort 2 | Mean Change From Baseline in Serum Carcinoembryonic Antigen (CEA) After Administration of NV1020 and 2 Cycles of Chemotherapy | Mean Change - Follow-up 2 | 134.7 ng/mL | — |
| Dose Cohort 2 | Mean Change From Baseline in Serum Carcinoembryonic Antigen (CEA) After Administration of NV1020 and 2 Cycles of Chemotherapy | Mean Change - Chemo visit 1 | 96.0 ng/mL | Standard Deviation 106.1 |
| Dose Cohort 2 | Mean Change From Baseline in Serum Carcinoembryonic Antigen (CEA) After Administration of NV1020 and 2 Cycles of Chemotherapy | Mean Change - Follow-up 1 | 615.6 ng/mL | Standard Deviation 867.5 |
| Dose Cohort 2 | Mean Change From Baseline in Serum Carcinoembryonic Antigen (CEA) After Administration of NV1020 and 2 Cycles of Chemotherapy | Mean Change - Chemo visit 2 | 194.4 ng/mL | Standard Deviation 212.8 |
| Dose Cohort 2 | Mean Change From Baseline in Serum Carcinoembryonic Antigen (CEA) After Administration of NV1020 and 2 Cycles of Chemotherapy | Mean Change - Follow-up 3 | NA ng/mL | — |
| Dose Cohort 3 | Mean Change From Baseline in Serum Carcinoembryonic Antigen (CEA) After Administration of NV1020 and 2 Cycles of Chemotherapy | Mean Change - Follow-up 3 | 16.5 ng/mL | — |
| Dose Cohort 3 | Mean Change From Baseline in Serum Carcinoembryonic Antigen (CEA) After Administration of NV1020 and 2 Cycles of Chemotherapy | Mean Baseline CEA | 121.6 ng/mL | Standard Deviation 230.3 |
| Dose Cohort 3 | Mean Change From Baseline in Serum Carcinoembryonic Antigen (CEA) After Administration of NV1020 and 2 Cycles of Chemotherapy | Mean Change - Chemo visit 1 | 8.6 ng/mL | Standard Deviation 17 |
| Dose Cohort 3 | Mean Change From Baseline in Serum Carcinoembryonic Antigen (CEA) After Administration of NV1020 and 2 Cycles of Chemotherapy | Mean Change - Chemo visit 2 | -0.6 ng/mL | — |
| Dose Cohort 3 | Mean Change From Baseline in Serum Carcinoembryonic Antigen (CEA) After Administration of NV1020 and 2 Cycles of Chemotherapy | Mean Change - Follow-up 1 | 5.4 ng/mL | Standard Deviation 5.8 |
| Dose Cohort 3 | Mean Change From Baseline in Serum Carcinoembryonic Antigen (CEA) After Administration of NV1020 and 2 Cycles of Chemotherapy | Mean Change - Follow-up 2 | 1.8 ng/mL | Standard Deviation 3.5 |
| Dose Cohort 3 | Mean Change From Baseline in Serum Carcinoembryonic Antigen (CEA) After Administration of NV1020 and 2 Cycles of Chemotherapy | Mean Change - Follow-up 4 | -1.7 ng/mL | — |
| Dose Cohort 4 | Mean Change From Baseline in Serum Carcinoembryonic Antigen (CEA) After Administration of NV1020 and 2 Cycles of Chemotherapy | Mean Change - Follow-up 1 | 97.0 ng/mL | Standard Deviation 334.1 |
| Dose Cohort 4 | Mean Change From Baseline in Serum Carcinoembryonic Antigen (CEA) After Administration of NV1020 and 2 Cycles of Chemotherapy | Mean Change - Chemo visit 2 | 98.2 ng/mL | Standard Deviation 254.1 |
| Dose Cohort 4 | Mean Change From Baseline in Serum Carcinoembryonic Antigen (CEA) After Administration of NV1020 and 2 Cycles of Chemotherapy | Mean Change - Follow-up 3 | -52.3 ng/mL | Standard Deviation 94.9 |
| Dose Cohort 4 | Mean Change From Baseline in Serum Carcinoembryonic Antigen (CEA) After Administration of NV1020 and 2 Cycles of Chemotherapy | Mean Change - Chemo visit 1 | 165.6 ng/mL | Standard Deviation 410.5 |
| Dose Cohort 4 | Mean Change From Baseline in Serum Carcinoembryonic Antigen (CEA) After Administration of NV1020 and 2 Cycles of Chemotherapy | Mean Baseline CEA | 181.7 ng/mL | Standard Deviation 373.3 |
| Dose Cohort 4 | Mean Change From Baseline in Serum Carcinoembryonic Antigen (CEA) After Administration of NV1020 and 2 Cycles of Chemotherapy | Mean Change - Follow-up 4 | 290.9 ng/mL | Standard Deviation 447.8 |
| Dose Cohort 4 | Mean Change From Baseline in Serum Carcinoembryonic Antigen (CEA) After Administration of NV1020 and 2 Cycles of Chemotherapy | Mean Change - Follow-up 2 | 97.3 ng/mL | Standard Deviation 311.9 |
Secondary
Pharmacodynamic Effects of NV1020: NV1020 Neutralizing Antibody Titer Assay
Mean change from baseline in NV1020 neutralizing antibody titer by dose cohort
Time frame: Screening, Chemo Visit 1, Follow-up Visits 1 (1 week post end of treatment), 2 (+6M), 3 (+9M), 4 (+12M)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Patients | Pharmacodynamic Effects of NV1020: NV1020 Neutralizing Antibody Titer Assay | Mean Change - Follow-up Visit 3 | NA antibody titer | — |
| All Patients | Pharmacodynamic Effects of NV1020: NV1020 Neutralizing Antibody Titer Assay | Mean Change - Follow-up Visit 4 | NA antibody titer | — |
| All Patients | Pharmacodynamic Effects of NV1020: NV1020 Neutralizing Antibody Titer Assay | Mean Change - Chemotherapy Visit 1 | 1341 antibody titer | Standard Deviation 914 |
| All Patients | Pharmacodynamic Effects of NV1020: NV1020 Neutralizing Antibody Titer Assay | Mean Baseline Neutralizing Antibody | 282.7 antibody titer | Standard Deviation 96.4 |
| All Patients | Pharmacodynamic Effects of NV1020: NV1020 Neutralizing Antibody Titer Assay | Mean Change - Follow-up Visit 1 | 1231 antibody titer | Standard Deviation 1382 |
| All Patients | Pharmacodynamic Effects of NV1020: NV1020 Neutralizing Antibody Titer Assay | Mean Change - Follow-up Visit 2 | 824 antibody titer | Standard Deviation 622 |
| Dose Cohort 2 | Pharmacodynamic Effects of NV1020: NV1020 Neutralizing Antibody Titer Assay | Mean Change - Follow-up Visit 2 | 1152 antibody titer | — |
| Dose Cohort 2 | Pharmacodynamic Effects of NV1020: NV1020 Neutralizing Antibody Titer Assay | Mean Change - Chemotherapy Visit 1 | 1061 antibody titer | Standard Deviation 1430 |
| Dose Cohort 2 | Pharmacodynamic Effects of NV1020: NV1020 Neutralizing Antibody Titer Assay | Mean Change - Follow-up Visit 1 | 950 antibody titer | Standard Deviation 1344 |
| Dose Cohort 2 | Pharmacodynamic Effects of NV1020: NV1020 Neutralizing Antibody Titer Assay | Mean Baseline Neutralizing Antibody | 1242.7 antibody titer | Standard Deviation 1585.2 |
| Dose Cohort 2 | Pharmacodynamic Effects of NV1020: NV1020 Neutralizing Antibody Titer Assay | Mean Change - Follow-up Visit 3 | NA antibody titer | — |
| Dose Cohort 2 | Pharmacodynamic Effects of NV1020: NV1020 Neutralizing Antibody Titer Assay | Mean Change - Follow-up Visit 4 | NA antibody titer | — |
| Dose Cohort 3 | Pharmacodynamic Effects of NV1020: NV1020 Neutralizing Antibody Titer Assay | Mean Change - Chemotherapy Visit 1 | 4926 antibody titer | Standard Deviation 1444 |
| Dose Cohort 3 | Pharmacodynamic Effects of NV1020: NV1020 Neutralizing Antibody Titer Assay | Mean Change - Follow-up Visit 4 | -543.1 antibody titer | — |
| Dose Cohort 3 | Pharmacodynamic Effects of NV1020: NV1020 Neutralizing Antibody Titer Assay | Mean Change - Follow-up Visit 2 | 1887 antibody titer | Standard Deviation 1133 |
| Dose Cohort 3 | Pharmacodynamic Effects of NV1020: NV1020 Neutralizing Antibody Titer Assay | Mean Baseline Neutralizing Antibody | 1006.6 antibody titer | Standard Deviation 844.6 |
| Dose Cohort 3 | Pharmacodynamic Effects of NV1020: NV1020 Neutralizing Antibody Titer Assay | Mean Change - Follow-up Visit 3 | 450 antibody titer | — |
| Dose Cohort 3 | Pharmacodynamic Effects of NV1020: NV1020 Neutralizing Antibody Titer Assay | Mean Change - Follow-up Visit 1 | 2154 antibody titer | Standard Deviation 473 |
| Dose Cohort 4 | Pharmacodynamic Effects of NV1020: NV1020 Neutralizing Antibody Titer Assay | Mean Change - Follow-up Visit 4 | 403 antibody titer | Standard Deviation 374 |
| Dose Cohort 4 | Pharmacodynamic Effects of NV1020: NV1020 Neutralizing Antibody Titer Assay | Mean Baseline Neutralizing Antibody | 334.2 antibody titer | Standard Deviation 309.1 |
| Dose Cohort 4 | Pharmacodynamic Effects of NV1020: NV1020 Neutralizing Antibody Titer Assay | Mean Change - Chemotherapy Visit 1 | 3481 antibody titer | Standard Deviation 2251 |
| Dose Cohort 4 | Pharmacodynamic Effects of NV1020: NV1020 Neutralizing Antibody Titer Assay | Mean Change - Follow-up Visit 1 | 2389 antibody titer | Standard Deviation 1736 |
| Dose Cohort 4 | Pharmacodynamic Effects of NV1020: NV1020 Neutralizing Antibody Titer Assay | Mean Change - Follow-up Visit 2 | 1292 antibody titer | Standard Deviation 1245 |
| Dose Cohort 4 | Pharmacodynamic Effects of NV1020: NV1020 Neutralizing Antibody Titer Assay | Mean Change - Follow-up Visit 3 | 1029 antibody titer | Standard Deviation 863 |
Secondary
Pharmacodynamic Effects of NV1020: Serum Cytokines (IL-6)
Median change from baseline of Interleukin-6 (IL-6) 8 hours post NV1020 infusion (Visits 1, 3, 5, 7)
Time frame: Baseline, after each NV1020 infusion (Visit 1, Visit 3, Visit 5, Visit 7)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| All Patients | Pharmacodynamic Effects of NV1020: Serum Cytokines (IL-6) | Median change - Visit 5 (post 8 hr) | 12.1 pg/mL |
| All Patients | Pharmacodynamic Effects of NV1020: Serum Cytokines (IL-6) | Median change - Visit 1 (post 8 hr) | 1.7 pg/mL |
| All Patients | Pharmacodynamic Effects of NV1020: Serum Cytokines (IL-6) | Median change - Visit 7 (post 8 hr) | 34.7 pg/mL |
| All Patients | Pharmacodynamic Effects of NV1020: Serum Cytokines (IL-6) | Median change - Visit 3 (post 8 hr) | 29.8 pg/mL |
| All Patients | Pharmacodynamic Effects of NV1020: Serum Cytokines (IL-6) | Median Baseline IL-6 | 6.9 pg/mL |
| Dose Cohort 2 | Pharmacodynamic Effects of NV1020: Serum Cytokines (IL-6) | Median change - Visit 3 (post 8 hr) | 3.0 pg/mL |
| Dose Cohort 2 | Pharmacodynamic Effects of NV1020: Serum Cytokines (IL-6) | Median change - Visit 5 (post 8 hr) | 14.5 pg/mL |
| Dose Cohort 2 | Pharmacodynamic Effects of NV1020: Serum Cytokines (IL-6) | Median change - Visit 7 (post 8 hr) | 8.5 pg/mL |
| Dose Cohort 2 | Pharmacodynamic Effects of NV1020: Serum Cytokines (IL-6) | Median change - Visit 1 (post 8 hr) | 6.0 pg/mL |
| Dose Cohort 2 | Pharmacodynamic Effects of NV1020: Serum Cytokines (IL-6) | Median Baseline IL-6 | 11.0 pg/mL |
| Dose Cohort 3 | Pharmacodynamic Effects of NV1020: Serum Cytokines (IL-6) | Median change - Visit 3 (post 8 hr) | 50.2 pg/mL |
| Dose Cohort 3 | Pharmacodynamic Effects of NV1020: Serum Cytokines (IL-6) | Median Baseline IL-6 | 15.5 pg/mL |
| Dose Cohort 3 | Pharmacodynamic Effects of NV1020: Serum Cytokines (IL-6) | Median change - Visit 1 (post 8 hr) | 16.5 pg/mL |
| Dose Cohort 3 | Pharmacodynamic Effects of NV1020: Serum Cytokines (IL-6) | Median change - Visit 5 (post 8 hr) | 63.0 pg/mL |
| Dose Cohort 3 | Pharmacodynamic Effects of NV1020: Serum Cytokines (IL-6) | Median change - Visit 7 (post 8 hr) | 11.3 pg/mL |
| Dose Cohort 4 | Pharmacodynamic Effects of NV1020: Serum Cytokines (IL-6) | Median change - Visit 5 (post 8 hr) | 32.2 pg/mL |
| Dose Cohort 4 | Pharmacodynamic Effects of NV1020: Serum Cytokines (IL-6) | Median change - Visit 1 (post 8 hr) | 32.1 pg/mL |
| Dose Cohort 4 | Pharmacodynamic Effects of NV1020: Serum Cytokines (IL-6) | Median Baseline IL-6 | 6.2 pg/mL |
| Dose Cohort 4 | Pharmacodynamic Effects of NV1020: Serum Cytokines (IL-6) | Median change - Visit 3 (post 8 hr) | 60.6 pg/mL |
| Dose Cohort 4 | Pharmacodynamic Effects of NV1020: Serum Cytokines (IL-6) | Median change - Visit 7 (post 8 hr) | 43.0 pg/mL |
Secondary
Pharmacodynamic Effects of NV1020: Serum Cytokines (INF Gamma)
Median change from baseline of Interferon (INF) gamma 8 hours post NV1020 infusion (Visits 1, 3, 5, 7)
Time frame: Baseline, after each NV1020 infusion (Visit 1, Visit 3, Visit 5, Visit 7)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| All Patients | Pharmacodynamic Effects of NV1020: Serum Cytokines (INF Gamma) | Median Change - Visit 5 (post 8 hr) | 2.5 pg/mL |
| All Patients | Pharmacodynamic Effects of NV1020: Serum Cytokines (INF Gamma) | Median Change - Visit 1 (post 8 hr) | 5.8 pg/mL |
| All Patients | Pharmacodynamic Effects of NV1020: Serum Cytokines (INF Gamma) | Median Change - Visit 7 (post 8 hr) | 1.3 pg/mL |
| All Patients | Pharmacodynamic Effects of NV1020: Serum Cytokines (INF Gamma) | Median Change - Visit 3 (post 8 hr) | 7.7 pg/mL |
| All Patients | Pharmacodynamic Effects of NV1020: Serum Cytokines (INF Gamma) | Median Baseline INF gamma | 1.1 pg/mL |
| Dose Cohort 2 | Pharmacodynamic Effects of NV1020: Serum Cytokines (INF Gamma) | Median Change - Visit 3 (post 8 hr) | 0.8 pg/mL |
| Dose Cohort 2 | Pharmacodynamic Effects of NV1020: Serum Cytokines (INF Gamma) | Median Change - Visit 5 (post 8 hr) | 0.2 pg/mL |
| Dose Cohort 2 | Pharmacodynamic Effects of NV1020: Serum Cytokines (INF Gamma) | Median Change - Visit 7 (post 8 hr) | -0.3 pg/mL |
| Dose Cohort 2 | Pharmacodynamic Effects of NV1020: Serum Cytokines (INF Gamma) | Median Change - Visit 1 (post 8 hr) | 0.5 pg/mL |
| Dose Cohort 2 | Pharmacodynamic Effects of NV1020: Serum Cytokines (INF Gamma) | Median Baseline INF gamma | 0.9 pg/mL |
| Dose Cohort 3 | Pharmacodynamic Effects of NV1020: Serum Cytokines (INF Gamma) | Median Change - Visit 3 (post 8 hr) | 36.0 pg/mL |
| Dose Cohort 3 | Pharmacodynamic Effects of NV1020: Serum Cytokines (INF Gamma) | Median Baseline INF gamma | 0.7 pg/mL |
| Dose Cohort 3 | Pharmacodynamic Effects of NV1020: Serum Cytokines (INF Gamma) | Median Change - Visit 1 (post 8 hr) | 4.7 pg/mL |
| Dose Cohort 3 | Pharmacodynamic Effects of NV1020: Serum Cytokines (INF Gamma) | Median Change - Visit 5 (post 8 hr) | 10.3 pg/mL |
| Dose Cohort 3 | Pharmacodynamic Effects of NV1020: Serum Cytokines (INF Gamma) | Median Change - Visit 7 (post 8 hr) | 7.6 pg/mL |
| Dose Cohort 4 | Pharmacodynamic Effects of NV1020: Serum Cytokines (INF Gamma) | Median Change - Visit 5 (post 8 hr) | 18.8 pg/mL |
| Dose Cohort 4 | Pharmacodynamic Effects of NV1020: Serum Cytokines (INF Gamma) | Median Change - Visit 1 (post 8 hr) | 22.9 pg/mL |
| Dose Cohort 4 | Pharmacodynamic Effects of NV1020: Serum Cytokines (INF Gamma) | Median Baseline INF gamma | 0.6 pg/mL |
| Dose Cohort 4 | Pharmacodynamic Effects of NV1020: Serum Cytokines (INF Gamma) | Median Change - Visit 3 (post 8 hr) | 51.8 pg/mL |
| Dose Cohort 4 | Pharmacodynamic Effects of NV1020: Serum Cytokines (INF Gamma) | Median Change - Visit 7 (post 8 hr) | 18.1 pg/mL |
Secondary
Pharmacodynamic Effects of NV1020: Serum Cytokines (TNF-alpha)
Median change from baseline of tumor necrosis factor (TNF-alpha) 8 hours post NV1020 infusion (Visits 1, 3, 5, 7)
Time frame: Baseline, after each NV1020 infusion (Visit 1, Visit 3, Visit 5, Visit 7)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| All Patients | Pharmacodynamic Effects of NV1020: Serum Cytokines (TNF-alpha) | Median change - Visit 5 (post 8 hr) | 2.3 pg/mL |
| All Patients | Pharmacodynamic Effects of NV1020: Serum Cytokines (TNF-alpha) | Median change - Visit 7 (post 8 hr) | 2.2 pg/mL |
| All Patients | Pharmacodynamic Effects of NV1020: Serum Cytokines (TNF-alpha) | Median change - Visit 3 (post 8 hr) | 3.6 pg/mL |
| All Patients | Pharmacodynamic Effects of NV1020: Serum Cytokines (TNF-alpha) | Median Baseline TNF-alpha | 1.8 pg/mL |
| All Patients | Pharmacodynamic Effects of NV1020: Serum Cytokines (TNF-alpha) | Median change - Visit 1 (post 8 hr) | 0.2 pg/mL |
| Dose Cohort 2 | Pharmacodynamic Effects of NV1020: Serum Cytokines (TNF-alpha) | Median change - Visit 3 (post 8 hr) | 0.4 pg/mL |
| Dose Cohort 2 | Pharmacodynamic Effects of NV1020: Serum Cytokines (TNF-alpha) | Median Baseline TNF-alpha | 2.0 pg/mL |
| Dose Cohort 2 | Pharmacodynamic Effects of NV1020: Serum Cytokines (TNF-alpha) | Median change - Visit 1 (post 8 hr) | 1.4 pg/mL |
| Dose Cohort 2 | Pharmacodynamic Effects of NV1020: Serum Cytokines (TNF-alpha) | Median change - Visit 5 (post 8 hr) | 1.3 pg/mL |
| Dose Cohort 2 | Pharmacodynamic Effects of NV1020: Serum Cytokines (TNF-alpha) | Median change - Visit 7 (post 8 hr) | 1.5 pg/mL |
| Dose Cohort 3 | Pharmacodynamic Effects of NV1020: Serum Cytokines (TNF-alpha) | Median Baseline TNF-alpha | 2.5 pg/mL |
| Dose Cohort 3 | Pharmacodynamic Effects of NV1020: Serum Cytokines (TNF-alpha) | Median change - Visit 3 (post 8 hr) | 2.3 pg/mL |
| Dose Cohort 3 | Pharmacodynamic Effects of NV1020: Serum Cytokines (TNF-alpha) | Median change - Visit 7 (post 8 hr) | 0.8 pg/mL |
| Dose Cohort 3 | Pharmacodynamic Effects of NV1020: Serum Cytokines (TNF-alpha) | Median change - Visit 5 (post 8 hr) | 1.8 pg/mL |
| Dose Cohort 3 | Pharmacodynamic Effects of NV1020: Serum Cytokines (TNF-alpha) | Median change - Visit 1 (post 8 hr) | -0.2 pg/mL |
| Dose Cohort 4 | Pharmacodynamic Effects of NV1020: Serum Cytokines (TNF-alpha) | Median change - Visit 5 (post 8 hr) | 5.5 pg/mL |
| Dose Cohort 4 | Pharmacodynamic Effects of NV1020: Serum Cytokines (TNF-alpha) | Median Baseline TNF-alpha | 1.3 pg/mL |
| Dose Cohort 4 | Pharmacodynamic Effects of NV1020: Serum Cytokines (TNF-alpha) | Median change - Visit 3 (post 8 hr) | 5.9 pg/mL |
| Dose Cohort 4 | Pharmacodynamic Effects of NV1020: Serum Cytokines (TNF-alpha) | Median change - Visit 7 (post 8 hr) | 5.7 pg/mL |
| Dose Cohort 4 | Pharmacodynamic Effects of NV1020: Serum Cytokines (TNF-alpha) | Median change - Visit 1 (post 8 hr) | 2.4 pg/mL |
Secondary
Time to Disease Progression; Survival Time
Progression assessed from CT and PET measurements and is determined as an increase of greater than or equal to 25% in the sum of the products of perpendicular diameters of all tumors, or the appearance of any new lesion.
Time frame: Progression: Chemo visit 1, FU1 (1 week post treatment), FU2 (+6M), FU3 (+9M), FU4 (+12M); Survival: death of patient
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| All Patients | Time to Disease Progression; Survival Time | Median time to progression | 3.5 months |
| All Patients | Time to Disease Progression; Survival Time | Median survival time | 12.4 months |
| Dose Cohort 2 | Time to Disease Progression; Survival Time | Median time to progression | 6.4 months |
| Dose Cohort 2 | Time to Disease Progression; Survival Time | Median survival time | 11.6 months |