Solid Tumor Malignancies
Conditions
Keywords
Phase 1, Metastatic Disease, Solid Tumor, Malignancy, Metastases, Clinical Trial, Hypoxia, Necrosis, Intratumoral, Locally advanced cancer, Immunotherapy, Sarcoma, Chordoma, Bacteriolytic
Brief summary
This protocol will examine the safety of intratumoral administration of Clostridium Novyi-NT spores in patients with treatment-refractory solid tumor malignancies. This investigational study will measure anti-tumor activity of C. novyi-NT administered intratumoral in patients with treatment-refractory solid tumor malignancies.
Interventions
BIOLOGICALClostridium novyi-NT spores
Phase 1 study: It will be an escalating dose design, with no intracohort escalation. The first cohort dose will begin at 1 x 10(4) spores/kg and will escalate by tripling through 5 cohorts up to 100 x 10(4) spores/kg.
Sponsors
BioMed Valley Discoveries, Inc
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. Diagnosis of an advanced solid tumor malignancy. There must be a target tumor which is measureable, palpable or clearly identifiable under ultrasound or radiographic guidance and amenable to percutaneous injection of C. novyi-NT spores. The targeted lesion must have a longest diameter ≥ 1 cm and ≤ 12 cm and be measurable as defined by RECIST 1.1 criteria. The target lesion must not be located in either the thoracic, abdominal or pelvic cavities or in the brain. There must be no clinical, no functional, and no radiographic evidence of bone involvement at the site of the target lesion. 2. History of prior treatment with at least one line of systemic anticancer therapy, when an approved systemic therapy is available, and no curative option is available for continued treatment. 3. At least 4 weeks have elapsed since the completion of major surgery, and the patient has fully recovered from this surgery and any post-surgical complications. 4. Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less. 5. Patient is at least 18 years of age. 6. Patient is capable of giving informed consent. 7. Patient of childbearing potential (defined by the clinical sites' standards) is using adequate birth control measures (e.g., barrier method with spermicide; intrauterine device; implantable or injectable hormonal contraceptives; surgical sterilization) for the duration of the study and will continue to use such precautions for 12 months after receiving treatment. 8. Patient has no significant valvular heart disease (trace or mild valvular stenosis or regurgitation is allowed). 9. Patient is able to stay within 45 minutes driving time of an emergency room for 28 days after doing. 10. The patient has a caregiver for 28 days after dosing.
Exclusion criteria
1. Positive pregnancy test. 2. Serum creatinine level \> 1.5 x the upper limit of normal (ULN), chronic renal failure requiring hemodialysis or peritoneal dialysis. 3. Patient has any of the following hematologic parameters: * Platelet count equal to or less than 100,000/mm3 * Hemoglobin less than 9.0 g/dL * Absolute neutrophil count (ANC) less than 1,000 /mm3 4. Oxygen saturation (Sp02) of less than 95% on room air. 5. Mean arterial blood pressure (BP) of less than 70 mmHg. 6. Glasgow Coma Score (GCS) of less than 15. 7. Treatment with an investigational drug within the past 30 days or 5 half-lives of that drug, whichever is shorter. 8. Documented primary brain malignancy or brain metastases. 9. Clinically significant ascites or clinical evidence or history of portosystemic hypertension or cirrhosis. 10. Laboratory evidence of hepatic dysfunction indicated by any of the following: * Bilirubin ≥ 1.5 x the ULN * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) above 2.5X the ULN * Alkaline phosphatase above 2.5X the ULN * International normalized ratio (INR) greater than 1.3 11. Patient has a foreign body which in the opinion of the treating investigator could be difficult to manage in case of infection (e.g. prosthetic hip). 12. Clinically significant pleural effusion. 13. Clinically significant pericardial effusion, circumferential pericardial effusion, or any effusion greater than 1.0 cm at any location around the heart. 14. Need for ongoing treatment with an immunosuppressive agent. 15. History of solid organ transplantation (with the exception of a corneal transplant \> 3 months prior to screening). 16. History of an ischemic insult in the previous 12 months (myocardial infarction, cerebral vascular accident, ischemic tissue from injury, transient ischemic attack. 17. History of a significant medical illness deemed by the PI or local investigators as unsuitable for the trial. For example: i. Symptomatic congestive heart failure ii. Psychiatric Illness/social situation that may make study dangerous iii. Unstable angina pectoris 18. Asplenia. 19. Antibiotic allergies that would preclude treatment for a C. novyi-NT infection. 20. Treatment with antibiotics within 2 weeks (14 days) of dosing. 21. Active and clinically significant systemic or localized infection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Treatment-emergent Adverse Events (TEAE) | From screening until follow-up visit (up to 12 months) | To determine the safety profile of C. novyi-NT in humans with treatment-refractory solid tumor malignancies when administered as a single IT injection. CTCAE: Common Terminology Criteria for Adverse Events |
| Number of Patients With Adverse Events Qualified as Dose Limiting Toxicities (DLTs) | From screening until follow-up visit (up to 12 months) | To determine the DLTs of C. novyi-NT in humans with treatment-refractory solid tumor malignancies when administered as a single IT injection. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Overall RECIST Response | At follow up (at 1 and 2, 4, and 8 months (±2 days) after dosing) | To document preliminary anti-tumor activity of an overall response after administering a single IT injection of C. novyi-NT in humans with treatment-refractory solid tumor malignancies. The evaluation of anti-tumor activity included an overall response. |
| Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | At Screening, at Days -1 to 0, at Days 1, 2, 3, 4, 5, 7, at follow up (at 2 months (±2 days) after dosing) | To study the presence of circulating C. novyi-NT spores after administration as a single IT injection to humans with treatment-refractory solid tumor malignancies. |
| Percentage Change in Tumor Size From Baseline of the Target Injected Lesion, Measured by Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans | At screening, at follow up (at 1, 2, 4, and 8 months (±2 days) after dosing) | To document preliminary anti-tumor activity of the injected lesion after administering a single IT injection of C. novyi-NT in humans with treatment-refractory solid tumor malignancies. Response and progression was evaluated using the international criteria proposed by the RECIST 1.1. Objective responses were measured by serial CT or MRI scans of the injected lesion and sites of metastatic involvement. Overall response, based on CT/MRI scan results, was based on observation of measurable and non-measurable disease as compared to baseline and nadir in target and non-target tumors per RECIST 1.1. Change from baseline is presented. |
| Number of Patients With Systemic Tumor Antigen Specific T-cell Responses | 2 years | The host immune and inflammatory response to C. novyi-NT spores was measured in routine blood sampling over the course of the study. Release of T-cell cytokines and effector molecules (interferon \[IFN\]-γ , Granzyme B, and tumor necrosis factor \[TNF\]-α) from the patient's own peripheral blood mononuclear cells (PBMCs) treated with allogenic tumor cell line lysates were quantified by Enzyme-Linked Immunosorbent Spot (ELISPOT) assays. A positive response was defined as a frequency that is significantly (p \<0.05, two-tailed t-test) greater than the mean of control no-antigen wells and detectable (i.e., \>1:100,000). No patients were analyzed for Cohort 1 and Cohort 2 based on the original study protocol. |
| Number of Patients With Local Tumor-specific T-cell Responses | 2 years | The host immune and inflammatory response to C. novyi-NT spores was measured in routine blood sampling over the course of the study. Immunostaining for tumor infiltrating cells was analyzed independently by 2 investigators. Respective counting of 3 slides per patient between 5 to 20 fields of vision at 200x were scored using the modified ALLRED scoring method. Respective counts were averaged in each case. Pre and post treatment needle biopsies from injected and non-injected tumors were stained for the presence of tumor infiltrating immune cells. No patients were analyzed for Cohort 1 and Cohort 2 based on the original study protocol. |
| Number of Patients With Cytokine Responses Analyzed | 2 years | The host immune and inflammatory response to C. novyi-NT spores was measured in routine blood sampling over the course of the study. The following table presents the data for the patients who had analyzable cytokine data. This table was included to simply indicate the number of patients who participated in the cytokine response analysis. |
| Number of Patients With RECIST Assessment on the Injected Lesion | At follow up (at 1 and 2, 4, and 8 months (±2 days) after dosing) | To document preliminary anti-tumor activity of the injected lesion after administering a single IT injection of C. novyi-NT in humans with treatment-refractory solid tumor malignancies. The evaluation of anti-tumor activity included a response for the injected lesion. Response and progression was evaluated using the international criteria proposed by the RECIST 1.1. Objective responses were measured by serial CT or MRI scans of the injected lesion and sites of metastatic involvement. Overall response, based on CT/MRI scan results, was based on observation of measurable and non-measurable disease as compared to baseline and nadir in target and non-target tumors per RECIST 1.1. |
Countries
United States
Participant flow
Recruitment details
This study was conducted at 7 study centers in the United States. A total of 24 patients were enrolled at 4 study centers. Three study centers did not enroll patients.
Pre-assignment details
Patients who provided informed consent underwent screening procedures within the 21 days preceding C. novyi-NT (Clostridium novyi-Non-Toxic) spore administration. Patients reported to the clinical site 24 hours prior to study Day 0 to reconfirm eligibility and for baseline assessments. Assessments were done as per the schedule of assessment.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 Cohort 1: 1 x 10\^4 spores | 3 |
| Cohort 2 Cohort 2: 3 x 10\^4 spores | 3 |
| Cohort 3 Cohort 3: 10 x 10\^4 spores | 4 |
| Cohort 4 Cohort 4: 30 x 10\^4 spores | 6 |
| Cohort 5 Cohort 5: 100 x 10\^4 spores | 6 |
| Cohort 6 Cohort 6: 300 x 10\^4 spores | 2 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Death | 0 | 1 | 0 | 1 | 0 | 0 |
| Overall Study | Disease progression | 0 | 0 | 2 | 0 | 3 | 2 |
| Overall Study | New therapy or study | 3 | 2 | 1 | 4 | 2 | 0 |
| Overall Study | Other | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal of consent | 0 | 0 | 1 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Cohort 5 | Cohort 6 | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 52.7 years STANDARD_DEVIATION 14.5 | 55.3 years STANDARD_DEVIATION 8.08 | 48.3 years STANDARD_DEVIATION 14.13 | 57.2 years STANDARD_DEVIATION 12.72 | 59.2 years STANDARD_DEVIATION 9.85 | 65.0 years STANDARD_DEVIATION 0 | 56.0 years STANDARD_DEVIATION 11.32 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 3 Participants | 4 Participants | 6 Participants | 5 Participants | 2 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 2 Participants | 4 Participants | 6 Participants | 6 Participants | 2 Participants | 22 Participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 3 Participants | 3 Participants | 2 Participants | 0 Participants | 12 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 1 Participants | 3 Participants | 4 Participants | 2 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 1 / 3 | 0 / 4 | 1 / 6 | 0 / 6 | 0 / 2 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 4 / 4 | 6 / 6 | 6 / 6 | 2 / 2 |
| serious Total, serious adverse events | 1 / 3 | 2 / 3 | 1 / 4 | 4 / 6 | 3 / 6 | 2 / 2 |
Outcome results
Primary
Number of Patients With Adverse Events Qualified as Dose Limiting Toxicities (DLTs)
To determine the DLTs of C. novyi-NT in humans with treatment-refractory solid tumor malignancies when administered as a single IT injection.
Time frame: From screening until follow-up visit (up to 12 months)
Population: The safety data set included all patients who received any amount of C. novyi-NT, IMP. Patients were included in the safety analysis according to the dose of IMP received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 | Number of Patients With Adverse Events Qualified as Dose Limiting Toxicities (DLTs) | Patient with Gas gangrene qualified as DLTs | 0 Patients |
| Cohort 1 | Number of Patients With Adverse Events Qualified as Dose Limiting Toxicities (DLTs) | Patient with any AEs qualified as DLTs | 0 Patients |
| Cohort 1 | Number of Patients With Adverse Events Qualified as Dose Limiting Toxicities (DLTs) | Patient with Sepsis qualified as DLTs | 0 Patients |
| Cohort 2 | Number of Patients With Adverse Events Qualified as Dose Limiting Toxicities (DLTs) | Patient with Gas gangrene qualified as DLTs | 0 Patients |
| Cohort 2 | Number of Patients With Adverse Events Qualified as Dose Limiting Toxicities (DLTs) | Patient with any AEs qualified as DLTs | 0 Patients |
| Cohort 2 | Number of Patients With Adverse Events Qualified as Dose Limiting Toxicities (DLTs) | Patient with Sepsis qualified as DLTs | 0 Patients |
| Cohort 3 | Number of Patients With Adverse Events Qualified as Dose Limiting Toxicities (DLTs) | Patient with Gas gangrene qualified as DLTs | 0 Patients |
| Cohort 3 | Number of Patients With Adverse Events Qualified as Dose Limiting Toxicities (DLTs) | Patient with any AEs qualified as DLTs | 0 Patients |
| Cohort 3 | Number of Patients With Adverse Events Qualified as Dose Limiting Toxicities (DLTs) | Patient with Sepsis qualified as DLTs | 0 Patients |
| Cohort 4 | Number of Patients With Adverse Events Qualified as Dose Limiting Toxicities (DLTs) | Patient with Gas gangrene qualified as DLTs | 0 Patients |
| Cohort 4 | Number of Patients With Adverse Events Qualified as Dose Limiting Toxicities (DLTs) | Patient with any AEs qualified as DLTs | 1 Patients |
| Cohort 4 | Number of Patients With Adverse Events Qualified as Dose Limiting Toxicities (DLTs) | Patient with Sepsis qualified as DLTs | 1 Patients |
| Cohort 5 | Number of Patients With Adverse Events Qualified as Dose Limiting Toxicities (DLTs) | Patient with Gas gangrene qualified as DLTs | 0 Patients |
| Cohort 5 | Number of Patients With Adverse Events Qualified as Dose Limiting Toxicities (DLTs) | Patient with any AEs qualified as DLTs | 0 Patients |
| Cohort 5 | Number of Patients With Adverse Events Qualified as Dose Limiting Toxicities (DLTs) | Patient with Sepsis qualified as DLTs | 0 Patients |
| Cohort 6 | Number of Patients With Adverse Events Qualified as Dose Limiting Toxicities (DLTs) | Patient with any AEs qualified as DLTs | 2 Patients |
| Cohort 6 | Number of Patients With Adverse Events Qualified as Dose Limiting Toxicities (DLTs) | Patient with Sepsis qualified as DLTs | 1 Patients |
| Cohort 6 | Number of Patients With Adverse Events Qualified as Dose Limiting Toxicities (DLTs) | Patient with Gas gangrene qualified as DLTs | 1 Patients |
Primary
Number of Patients With Treatment-emergent Adverse Events (TEAE)
To determine the safety profile of C. novyi-NT in humans with treatment-refractory solid tumor malignancies when administered as a single IT injection. CTCAE: Common Terminology Criteria for Adverse Events
Time frame: From screening until follow-up visit (up to 12 months)
Population: The safety data set included all patients who received any amount of C. novyi-NT, the investigational medicinal product (IMP). Patients were included in the safety analysis according to the dose of IMP received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 | Number of Patients With Treatment-emergent Adverse Events (TEAE) | Related TEAEs | 2 Patients |
| Cohort 1 | Number of Patients With Treatment-emergent Adverse Events (TEAE) | CTCAE Grade 2 TEAEs | 1 Patients |
| Cohort 1 | Number of Patients With Treatment-emergent Adverse Events (TEAE) | All TEAEs | 3 Patients |
| Cohort 1 | Number of Patients With Treatment-emergent Adverse Events (TEAE) | CTCAE Grade 1 TEAEs | 3 Patients |
| Cohort 1 | Number of Patients With Treatment-emergent Adverse Events (TEAE) | CTCAE Grade 3 TEAEs | 1 Patients |
| Cohort 1 | Number of Patients With Treatment-emergent Adverse Events (TEAE) | Life-Threatening TEAEs | 0 Patients |
| Cohort 1 | Number of Patients With Treatment-emergent Adverse Events (TEAE) | Deaths | 0 Patients |
| Cohort 1 | Number of Patients With Treatment-emergent Adverse Events (TEAE) | Serious TEAEs | 1 Patients |
| Cohort 2 | Number of Patients With Treatment-emergent Adverse Events (TEAE) | CTCAE Grade 1 TEAEs | 3 Patients |
| Cohort 2 | Number of Patients With Treatment-emergent Adverse Events (TEAE) | Serious TEAEs | 2 Patients |
| Cohort 2 | Number of Patients With Treatment-emergent Adverse Events (TEAE) | CTCAE Grade 3 TEAEs | 3 Patients |
| Cohort 2 | Number of Patients With Treatment-emergent Adverse Events (TEAE) | Deaths | 1 Patients |
| Cohort 2 | Number of Patients With Treatment-emergent Adverse Events (TEAE) | Life-Threatening TEAEs | 1 Patients |
| Cohort 2 | Number of Patients With Treatment-emergent Adverse Events (TEAE) | Related TEAEs | 3 Patients |
| Cohort 2 | Number of Patients With Treatment-emergent Adverse Events (TEAE) | All TEAEs | 3 Patients |
| Cohort 2 | Number of Patients With Treatment-emergent Adverse Events (TEAE) | CTCAE Grade 2 TEAEs | 3 Patients |
| Cohort 3 | Number of Patients With Treatment-emergent Adverse Events (TEAE) | Serious TEAEs | 1 Patients |
| Cohort 3 | Number of Patients With Treatment-emergent Adverse Events (TEAE) | Related TEAEs | 2 Patients |
| Cohort 3 | Number of Patients With Treatment-emergent Adverse Events (TEAE) | CTCAE Grade 1 TEAEs | 4 Patients |
| Cohort 3 | Number of Patients With Treatment-emergent Adverse Events (TEAE) | CTCAE Grade 2 TEAEs | 4 Patients |
| Cohort 3 | Number of Patients With Treatment-emergent Adverse Events (TEAE) | All TEAEs | 4 Patients |
| Cohort 3 | Number of Patients With Treatment-emergent Adverse Events (TEAE) | Life-Threatening TEAEs | 0 Patients |
| Cohort 3 | Number of Patients With Treatment-emergent Adverse Events (TEAE) | Deaths | 0 Patients |
| Cohort 3 | Number of Patients With Treatment-emergent Adverse Events (TEAE) | CTCAE Grade 3 TEAEs | 2 Patients |
| Cohort 4 | Number of Patients With Treatment-emergent Adverse Events (TEAE) | All TEAEs | 6 Patients |
| Cohort 4 | Number of Patients With Treatment-emergent Adverse Events (TEAE) | CTCAE Grade 2 TEAEs | 3 Patients |
| Cohort 4 | Number of Patients With Treatment-emergent Adverse Events (TEAE) | CTCAE Grade 3 TEAEs | 3 Patients |
| Cohort 4 | Number of Patients With Treatment-emergent Adverse Events (TEAE) | Serious TEAEs | 4 Patients |
| Cohort 4 | Number of Patients With Treatment-emergent Adverse Events (TEAE) | Life-Threatening TEAEs | 1 Patients |
| Cohort 4 | Number of Patients With Treatment-emergent Adverse Events (TEAE) | Deaths | 1 Patients |
| Cohort 4 | Number of Patients With Treatment-emergent Adverse Events (TEAE) | CTCAE Grade 1 TEAEs | 5 Patients |
| Cohort 4 | Number of Patients With Treatment-emergent Adverse Events (TEAE) | Related TEAEs | 4 Patients |
| Cohort 5 | Number of Patients With Treatment-emergent Adverse Events (TEAE) | CTCAE Grade 3 TEAEs | 3 Patients |
| Cohort 5 | Number of Patients With Treatment-emergent Adverse Events (TEAE) | All TEAEs | 6 Patients |
| Cohort 5 | Number of Patients With Treatment-emergent Adverse Events (TEAE) | Life-Threatening TEAEs | 0 Patients |
| Cohort 5 | Number of Patients With Treatment-emergent Adverse Events (TEAE) | Serious TEAEs | 3 Patients |
| Cohort 5 | Number of Patients With Treatment-emergent Adverse Events (TEAE) | CTCAE Grade 1 TEAEs | 6 Patients |
| Cohort 5 | Number of Patients With Treatment-emergent Adverse Events (TEAE) | Deaths | 0 Patients |
| Cohort 5 | Number of Patients With Treatment-emergent Adverse Events (TEAE) | CTCAE Grade 2 TEAEs | 2 Patients |
| Cohort 5 | Number of Patients With Treatment-emergent Adverse Events (TEAE) | Related TEAEs | 3 Patients |
| Cohort 6 | Number of Patients With Treatment-emergent Adverse Events (TEAE) | CTCAE Grade 3 TEAEs | 2 Patients |
| Cohort 6 | Number of Patients With Treatment-emergent Adverse Events (TEAE) | Deaths | 0 Patients |
| Cohort 6 | Number of Patients With Treatment-emergent Adverse Events (TEAE) | CTCAE Grade 1 TEAEs | 2 Patients |
| Cohort 6 | Number of Patients With Treatment-emergent Adverse Events (TEAE) | Life-Threatening TEAEs | 2 Patients |
| Cohort 6 | Number of Patients With Treatment-emergent Adverse Events (TEAE) | CTCAE Grade 2 TEAEs | 2 Patients |
| Cohort 6 | Number of Patients With Treatment-emergent Adverse Events (TEAE) | All TEAEs | 2 Patients |
| Cohort 6 | Number of Patients With Treatment-emergent Adverse Events (TEAE) | Serious TEAEs | 2 Patients |
| Cohort 6 | Number of Patients With Treatment-emergent Adverse Events (TEAE) | Related TEAEs | 2 Patients |
Secondary
Number of Patients With Cytokine Responses Analyzed
The host immune and inflammatory response to C. novyi-NT spores was measured in routine blood sampling over the course of the study. The following table presents the data for the patients who had analyzable cytokine data. This table was included to simply indicate the number of patients who participated in the cytokine response analysis.
Time frame: 2 years
Population: The efficacy data set or full analysis set consisted of all patients in the safety population who had both a baseline tumor assessment and at least one post-baseline tumor assessment. Patients were included in the analysis according to the dose of IMP received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | Number of Patients With Cytokine Responses Analyzed | 3 Patients |
| Cohort 2 | Number of Patients With Cytokine Responses Analyzed | 3 Patients |
| Cohort 3 | Number of Patients With Cytokine Responses Analyzed | 4 Patients |
| Cohort 4 | Number of Patients With Cytokine Responses Analyzed | 6 Patients |
| Cohort 5 | Number of Patients With Cytokine Responses Analyzed | 6 Patients |
| Cohort 6 | Number of Patients With Cytokine Responses Analyzed | 2 Patients |
Secondary
Number of Patients With Local Tumor-specific T-cell Responses
The host immune and inflammatory response to C. novyi-NT spores was measured in routine blood sampling over the course of the study. Immunostaining for tumor infiltrating cells was analyzed independently by 2 investigators. Respective counting of 3 slides per patient between 5 to 20 fields of vision at 200x were scored using the modified ALLRED scoring method. Respective counts were averaged in each case. Pre and post treatment needle biopsies from injected and non-injected tumors were stained for the presence of tumor infiltrating immune cells. No patients were analyzed for Cohort 1 and Cohort 2 based on the original study protocol.
Time frame: 2 years
Population: The efficacy data set or full analysis set consisted of all patients in the safety population who had both a baseline tumor assessment and at least one post-baseline tumor assessment. Patients were included in the analysis according to the dose of IMP received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | Number of Patients With Local Tumor-specific T-cell Responses | 0 Patients |
| Cohort 2 | Number of Patients With Local Tumor-specific T-cell Responses | 1 Patients |
| Cohort 3 | Number of Patients With Local Tumor-specific T-cell Responses | 0 Patients |
| Cohort 4 | Number of Patients With Local Tumor-specific T-cell Responses | 2 Patients |
Secondary
Number of Patients With Overall RECIST Response
To document preliminary anti-tumor activity of an overall response after administering a single IT injection of C. novyi-NT in humans with treatment-refractory solid tumor malignancies. The evaluation of anti-tumor activity included an overall response.
Time frame: At follow up (at 1 and 2, 4, and 8 months (±2 days) after dosing)
Population: The efficacy data set or full analysis set consisted of all patients in the safety population who had both a baseline tumor assessment and at least one post-baseline tumor assessment. Patients were included in the analysis according to the dose of IMP received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 | Number of Patients With Overall RECIST Response | Month 2, Partial Response | 0 Patients |
| Cohort 1 | Number of Patients With Overall RECIST Response | Month 8, Complete Response | 0 Patients |
| Cohort 1 | Number of Patients With Overall RECIST Response | Month 8, Stable Disease | 0 Patients |
| Cohort 1 | Number of Patients With Overall RECIST Response | Month 1, Complete Response | 0 Patients |
| Cohort 1 | Number of Patients With Overall RECIST Response | Month 1, Progressive Disease | 1 Patients |
| Cohort 1 | Number of Patients With Overall RECIST Response | Month 4, Stable Disease | 0 Patients |
| Cohort 1 | Number of Patients With Overall RECIST Response | Month 2, Complete Response | 0 Patients |
| Cohort 1 | Number of Patients With Overall RECIST Response | Month 1, Unknown | 0 Patients |
| Cohort 1 | Number of Patients With Overall RECIST Response | Month 2, Progressive Disease | 0 Patients |
| Cohort 1 | Number of Patients With Overall RECIST Response | Month 8, Partial Response | 0 Patients |
| Cohort 1 | Number of Patients With Overall RECIST Response | Month 4, Partial Response | 0 Patients |
| Cohort 1 | Number of Patients With Overall RECIST Response | Month 4, Complete Response | 0 Patients |
| Cohort 1 | Number of Patients With Overall RECIST Response | Month 1, Partial Response | 0 Patients |
| Cohort 1 | Number of Patients With Overall RECIST Response | Month 2, Unknown | 0 Patients |
| Cohort 1 | Number of Patients With Overall RECIST Response | Month 4, Unknown | 0 Patients |
| Cohort 1 | Number of Patients With Overall RECIST Response | Month 8, Unknown | 0 Patients |
| Cohort 1 | Number of Patients With Overall RECIST Response | Month 2, Stable Disease | 2 Patients |
| Cohort 1 | Number of Patients With Overall RECIST Response | Month 4, Progressive Disease | 0 Patients |
| Cohort 1 | Number of Patients With Overall RECIST Response | Month 1, Stable Disease | 2 Patients |
| Cohort 1 | Number of Patients With Overall RECIST Response | Month 8, Progressive Disease | 0 Patients |
| Cohort 2 | Number of Patients With Overall RECIST Response | Month 2, Unknown | 0 Patients |
| Cohort 2 | Number of Patients With Overall RECIST Response | Month 8, Progressive Disease | 0 Patients |
| Cohort 2 | Number of Patients With Overall RECIST Response | Month 4, Stable Disease | 0 Patients |
| Cohort 2 | Number of Patients With Overall RECIST Response | Month 4, Complete Response | 0 Patients |
| Cohort 2 | Number of Patients With Overall RECIST Response | Month 4, Partial Response | 0 Patients |
| Cohort 2 | Number of Patients With Overall RECIST Response | Month 1, Partial Response | 0 Patients |
| Cohort 2 | Number of Patients With Overall RECIST Response | Month 8, Stable Disease | 0 Patients |
| Cohort 2 | Number of Patients With Overall RECIST Response | Month 1, Stable Disease | 2 Patients |
| Cohort 2 | Number of Patients With Overall RECIST Response | Month 1, Progressive Disease | 1 Patients |
| Cohort 2 | Number of Patients With Overall RECIST Response | Month 8, Partial Response | 0 Patients |
| Cohort 2 | Number of Patients With Overall RECIST Response | Month 1, Unknown | 0 Patients |
| Cohort 2 | Number of Patients With Overall RECIST Response | Month 2, Complete Response | 0 Patients |
| Cohort 2 | Number of Patients With Overall RECIST Response | Month 8, Complete Response | 0 Patients |
| Cohort 2 | Number of Patients With Overall RECIST Response | Month 2, Partial Response | 0 Patients |
| Cohort 2 | Number of Patients With Overall RECIST Response | Month 1, Complete Response | 0 Patients |
| Cohort 2 | Number of Patients With Overall RECIST Response | Month 4, Unknown | 0 Patients |
| Cohort 2 | Number of Patients With Overall RECIST Response | Month 2, Stable Disease | 0 Patients |
| Cohort 2 | Number of Patients With Overall RECIST Response | Month 2, Progressive Disease | 2 Patients |
| Cohort 2 | Number of Patients With Overall RECIST Response | Month 8, Unknown | 0 Patients |
| Cohort 2 | Number of Patients With Overall RECIST Response | Month 4, Progressive Disease | 0 Patients |
| Cohort 3 | Number of Patients With Overall RECIST Response | Month 1, Stable Disease | 3 Patients |
| Cohort 3 | Number of Patients With Overall RECIST Response | Month 4, Complete Response | 0 Patients |
| Cohort 3 | Number of Patients With Overall RECIST Response | Month 2, Partial Response | 0 Patients |
| Cohort 3 | Number of Patients With Overall RECIST Response | Month 2, Progressive Disease | 0 Patients |
| Cohort 3 | Number of Patients With Overall RECIST Response | Month 4, Unknown | 0 Patients |
| Cohort 3 | Number of Patients With Overall RECIST Response | Month 4, Stable Disease | 0 Patients |
| Cohort 3 | Number of Patients With Overall RECIST Response | Month 8, Stable Disease | 0 Patients |
| Cohort 3 | Number of Patients With Overall RECIST Response | Month 2, Unknown | 0 Patients |
| Cohort 3 | Number of Patients With Overall RECIST Response | Month 2, Stable Disease | 0 Patients |
| Cohort 3 | Number of Patients With Overall RECIST Response | Month 1, Complete Response | 0 Patients |
| Cohort 3 | Number of Patients With Overall RECIST Response | Month 8, Progressive Disease | 0 Patients |
| Cohort 3 | Number of Patients With Overall RECIST Response | Month 1, Partial Response | 0 Patients |
| Cohort 3 | Number of Patients With Overall RECIST Response | Month 1, Unknown | 0 Patients |
| Cohort 3 | Number of Patients With Overall RECIST Response | Month 8, Complete Response | 0 Patients |
| Cohort 3 | Number of Patients With Overall RECIST Response | Month 1, Progressive Disease | 0 Patients |
| Cohort 3 | Number of Patients With Overall RECIST Response | Month 4, Progressive Disease | 0 Patients |
| Cohort 3 | Number of Patients With Overall RECIST Response | Month 2, Complete Response | 0 Patients |
| Cohort 3 | Number of Patients With Overall RECIST Response | Month 8, Partial Response | 0 Patients |
| Cohort 3 | Number of Patients With Overall RECIST Response | Month 4, Partial Response | 0 Patients |
| Cohort 3 | Number of Patients With Overall RECIST Response | Month 8, Unknown | 0 Patients |
| Cohort 4 | Number of Patients With Overall RECIST Response | Month 1, Partial Response | 0 Patients |
| Cohort 4 | Number of Patients With Overall RECIST Response | Month 8, Complete Response | 0 Patients |
| Cohort 4 | Number of Patients With Overall RECIST Response | Month 1, Complete Response | 0 Patients |
| Cohort 4 | Number of Patients With Overall RECIST Response | Month 1, Unknown | 0 Patients |
| Cohort 4 | Number of Patients With Overall RECIST Response | Month 1, Stable Disease | 6 Patients |
| Cohort 4 | Number of Patients With Overall RECIST Response | Month 1, Progressive Disease | 0 Patients |
| Cohort 4 | Number of Patients With Overall RECIST Response | Month 2, Complete Response | 0 Patients |
| Cohort 4 | Number of Patients With Overall RECIST Response | Month 2, Partial Response | 0 Patients |
| Cohort 4 | Number of Patients With Overall RECIST Response | Month 2, Stable Disease | 4 Patients |
| Cohort 4 | Number of Patients With Overall RECIST Response | Month 2, Progressive Disease | 1 Patients |
| Cohort 4 | Number of Patients With Overall RECIST Response | Month 2, Unknown | 0 Patients |
| Cohort 4 | Number of Patients With Overall RECIST Response | Month 4, Complete Response | 0 Patients |
| Cohort 4 | Number of Patients With Overall RECIST Response | Month 4, Partial Response | 0 Patients |
| Cohort 4 | Number of Patients With Overall RECIST Response | Month 4, Stable Disease | 1 Patients |
| Cohort 4 | Number of Patients With Overall RECIST Response | Month 4, Progressive Disease | 0 Patients |
| Cohort 4 | Number of Patients With Overall RECIST Response | Month 4, Unknown | 0 Patients |
| Cohort 4 | Number of Patients With Overall RECIST Response | Month 8, Partial Response | 0 Patients |
| Cohort 4 | Number of Patients With Overall RECIST Response | Month 8, Stable Disease | 0 Patients |
| Cohort 4 | Number of Patients With Overall RECIST Response | Month 8, Progressive Disease | 1 Patients |
| Cohort 4 | Number of Patients With Overall RECIST Response | Month 8, Unknown | 0 Patients |
| Cohort 5 | Number of Patients With Overall RECIST Response | Month 4, Stable Disease | 1 Patients |
| Cohort 5 | Number of Patients With Overall RECIST Response | Month 2, Progressive Disease | 2 Patients |
| Cohort 5 | Number of Patients With Overall RECIST Response | Month 2, Stable Disease | 3 Patients |
| Cohort 5 | Number of Patients With Overall RECIST Response | Month 2, Partial Response | 0 Patients |
| Cohort 5 | Number of Patients With Overall RECIST Response | Month 4, Progressive Disease | 0 Patients |
| Cohort 5 | Number of Patients With Overall RECIST Response | Month 4, Unknown | 0 Patients |
| Cohort 5 | Number of Patients With Overall RECIST Response | Month 2, Complete Response | 0 Patients |
| Cohort 5 | Number of Patients With Overall RECIST Response | Month 1, Progressive Disease | 0 Patients |
| Cohort 5 | Number of Patients With Overall RECIST Response | Month 1, Unknown | 0 Patients |
| Cohort 5 | Number of Patients With Overall RECIST Response | Month 8, Partial Response | 0 Patients |
| Cohort 5 | Number of Patients With Overall RECIST Response | Month 1, Stable Disease | 6 Patients |
| Cohort 5 | Number of Patients With Overall RECIST Response | Month 1, Partial Response | 0 Patients |
| Cohort 5 | Number of Patients With Overall RECIST Response | Month 8, Stable Disease | 0 Patients |
| Cohort 5 | Number of Patients With Overall RECIST Response | Month 1, Complete Response | 0 Patients |
| Cohort 5 | Number of Patients With Overall RECIST Response | Month 8, Complete Response | 0 Patients |
| Cohort 5 | Number of Patients With Overall RECIST Response | Month 8, Unknown | 0 Patients |
| Cohort 5 | Number of Patients With Overall RECIST Response | Month 8, Progressive Disease | 1 Patients |
| Cohort 5 | Number of Patients With Overall RECIST Response | Month 4, Partial Response | 0 Patients |
| Cohort 5 | Number of Patients With Overall RECIST Response | Month 4, Complete Response | 0 Patients |
| Cohort 5 | Number of Patients With Overall RECIST Response | Month 2, Unknown | 0 Patients |
| Cohort 6 | Number of Patients With Overall RECIST Response | Month 8, Progressive Disease | 0 Patients |
| Cohort 6 | Number of Patients With Overall RECIST Response | Month 4, Stable Disease | 0 Patients |
| Cohort 6 | Number of Patients With Overall RECIST Response | Month 2, Progressive Disease | 1 Patients |
| Cohort 6 | Number of Patients With Overall RECIST Response | Month 8, Partial Response | 0 Patients |
| Cohort 6 | Number of Patients With Overall RECIST Response | Month 2, Stable Disease | 0 Patients |
| Cohort 6 | Number of Patients With Overall RECIST Response | Month 4, Progressive Disease | 0 Patients |
| Cohort 6 | Number of Patients With Overall RECIST Response | Month 2, Unknown | 0 Patients |
| Cohort 6 | Number of Patients With Overall RECIST Response | Month 2, Partial Response | 0 Patients |
| Cohort 6 | Number of Patients With Overall RECIST Response | Month 1, Partial Response | 0 Patients |
| Cohort 6 | Number of Patients With Overall RECIST Response | Month 4, Partial Response | 0 Patients |
| Cohort 6 | Number of Patients With Overall RECIST Response | Month 8, Unknown | 0 Patients |
| Cohort 6 | Number of Patients With Overall RECIST Response | Month 4, Unknown | 0 Patients |
| Cohort 6 | Number of Patients With Overall RECIST Response | Month 2, Complete Response | 0 Patients |
| Cohort 6 | Number of Patients With Overall RECIST Response | Month 4, Complete Response | 0 Patients |
| Cohort 6 | Number of Patients With Overall RECIST Response | Month 1, Unknown | 1 Patients |
| Cohort 6 | Number of Patients With Overall RECIST Response | Month 8, Complete Response | 0 Patients |
| Cohort 6 | Number of Patients With Overall RECIST Response | Month 1, Progressive Disease | 0 Patients |
| Cohort 6 | Number of Patients With Overall RECIST Response | Month 8, Stable Disease | 0 Patients |
| Cohort 6 | Number of Patients With Overall RECIST Response | Month 1, Stable Disease | 0 Patients |
| Cohort 6 | Number of Patients With Overall RECIST Response | Month 1, Complete Response | 0 Patients |
Secondary
Number of Patients With RECIST Assessment on the Injected Lesion
To document preliminary anti-tumor activity of the injected lesion after administering a single IT injection of C. novyi-NT in humans with treatment-refractory solid tumor malignancies. The evaluation of anti-tumor activity included a response for the injected lesion. Response and progression was evaluated using the international criteria proposed by the RECIST 1.1. Objective responses were measured by serial CT or MRI scans of the injected lesion and sites of metastatic involvement. Overall response, based on CT/MRI scan results, was based on observation of measurable and non-measurable disease as compared to baseline and nadir in target and non-target tumors per RECIST 1.1.
Time frame: At follow up (at 1 and 2, 4, and 8 months (±2 days) after dosing)
Population: The efficacy data set or full analysis set consisted of all patients in the safety population who had both a baseline tumor assessment and at least one post-baseline tumor assessment. Patients were included in the analysis according to the dose of IMP received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 1, Stable Disease | 3 Patients |
| Cohort 1 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 1, Progressive Disease | 0 Patients |
| Cohort 1 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 4, Unknown | 0 Patients |
| Cohort 1 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 1, Complete Response | 0 Patients |
| Cohort 1 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 4, Progressive Disease | 0 Patients |
| Cohort 1 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 8, Stable Disease | 0 Patients |
| Cohort 1 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 2, Progressive Disease | 0 Patients |
| Cohort 1 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 1, Unknown | 0 Patients |
| Cohort 1 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 2, Stable Disease | 2 Patients |
| Cohort 1 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 4, Partial Response | 0 Patients |
| Cohort 1 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 4, Stable Disease | 0 Patients |
| Cohort 1 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 1, Partial Response | 0 Patients |
| Cohort 1 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 8, Partial Response | 0 Patients |
| Cohort 1 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 2, Complete Response | 0 Patients |
| Cohort 1 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 8, Unknown | 0 Patients |
| Cohort 1 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 4, Complete Response | 0 Patients |
| Cohort 1 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 2, Unknown | 0 Patients |
| Cohort 1 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 8, Progressive Disease | 0 Patients |
| Cohort 1 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 8, Complete Response | 0 Patients |
| Cohort 1 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 2, Partial Response | 0 Patients |
| Cohort 2 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 8, Stable Disease | 0 Patients |
| Cohort 2 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 2, Stable Disease | 0 Patients |
| Cohort 2 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 1, Stable Disease | 3 Patients |
| Cohort 2 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 1, Partial Response | 0 Patients |
| Cohort 2 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 4, Unknown | 0 Patients |
| Cohort 2 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 2, Progressive Disease | 2 Patients |
| Cohort 2 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 4, Complete Response | 0 Patients |
| Cohort 2 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 1, Complete Response | 0 Patients |
| Cohort 2 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 2, Unknown | 0 Patients |
| Cohort 2 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 4, Progressive Disease | 0 Patients |
| Cohort 2 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 2, Partial Response | 0 Patients |
| Cohort 2 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 1, Progressive Disease | 0 Patients |
| Cohort 2 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 4, Stable Disease | 0 Patients |
| Cohort 2 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 1, Unknown | 0 Patients |
| Cohort 2 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 4, Partial Response | 0 Patients |
| Cohort 2 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 8, Partial Response | 0 Patients |
| Cohort 2 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 2, Complete Response | 0 Patients |
| Cohort 2 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 8, Unknown | 0 Patients |
| Cohort 2 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 8, Progressive Disease | 0 Patients |
| Cohort 2 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 8, Complete Response | 0 Patients |
| Cohort 3 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 8, Complete Response | 0 Patients |
| Cohort 3 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 4, Complete Response | 0 Patients |
| Cohort 3 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 4, Stable Disease | 0 Patients |
| Cohort 3 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 4, Partial Response | 0 Patients |
| Cohort 3 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 1, Stable Disease | 3 Patients |
| Cohort 3 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 8, Stable Disease | 0 Patients |
| Cohort 3 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 1, Progressive Disease | 0 Patients |
| Cohort 3 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 1, Complete Response | 0 Patients |
| Cohort 3 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 8, Partial Response | 0 Patients |
| Cohort 3 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 1, Unknown | 0 Patients |
| Cohort 3 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 8, Unknown | 0 Patients |
| Cohort 3 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 2, Complete Response | 0 Patients |
| Cohort 3 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 1, Partial Response | 0 Patients |
| Cohort 3 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 2, Partial Response | 0 Patients |
| Cohort 3 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 8, Progressive Disease | 0 Patients |
| Cohort 3 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 4, Unknown | 0 Patients |
| Cohort 3 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 2, Stable Disease | 0 Patients |
| Cohort 3 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 2, Progressive Disease | 0 Patients |
| Cohort 3 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 4, Progressive Disease | 0 Patients |
| Cohort 3 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 2, Unknown | 0 Patients |
| Cohort 4 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 1, Unknown | 0 Patients |
| Cohort 4 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 4, Unknown | 0 Patients |
| Cohort 4 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 1, Complete Response | 0 Patients |
| Cohort 4 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 1, Partial Response | 0 Patients |
| Cohort 4 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 1, Stable Disease | 6 Patients |
| Cohort 4 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 1, Progressive Disease | 0 Patients |
| Cohort 4 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 4, Stable Disease | 1 Patients |
| Cohort 4 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 2, Complete Response | 0 Patients |
| Cohort 4 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 2, Partial Response | 0 Patients |
| Cohort 4 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 2, Progressive Disease | 1 Patients |
| Cohort 4 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 2, Stable Disease | 4 Patients |
| Cohort 4 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 2, Unknown | 0 Patients |
| Cohort 4 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 4, Complete Response | 0 Patients |
| Cohort 4 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 4, Partial Response | 0 Patients |
| Cohort 4 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 4, Progressive Disease | 0 Patients |
| Cohort 4 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 8, Complete Response | 0 Patients |
| Cohort 4 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 8, Partial Response | 0 Patients |
| Cohort 4 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 8, Stable Disease | 0 Patients |
| Cohort 4 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 8, Progressive Disease | 1 Patients |
| Cohort 4 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 8, Unknown | 0 Patients |
| Cohort 5 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 4, Progressive Disease | 0 Patients |
| Cohort 5 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 8, Partial Response | 0 Patients |
| Cohort 5 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 2, Partial Response | 0 Patients |
| Cohort 5 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 1, Progressive Disease | 0 Patients |
| Cohort 5 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 2, Stable Disease | 3 Patients |
| Cohort 5 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 1, Stable Disease | 6 Patients |
| Cohort 5 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 2, Complete Response | 0 Patients |
| Cohort 5 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 8, Stable Disease | 0 Patients |
| Cohort 5 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 1, Complete Response | 0 Patients |
| Cohort 5 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 8, Complete Response | 0 Patients |
| Cohort 5 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 1, Partial Response | 0 Patients |
| Cohort 5 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 2, Progressive Disease | 2 Patients |
| Cohort 5 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 8, Unknown | 0 Patients |
| Cohort 5 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 8, Progressive Disease | 1 Patients |
| Cohort 5 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 4, Unknown | 0 Patients |
| Cohort 5 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 4, Partial Response | 0 Patients |
| Cohort 5 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 1, Unknown | 0 Patients |
| Cohort 5 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 4, Complete Response | 0 Patients |
| Cohort 5 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 4, Stable Disease | 1 Patients |
| Cohort 5 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 2, Unknown | 0 Patients |
| Cohort 6 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 4, Stable Disease | 0 Patients |
| Cohort 6 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 2, Progressive Disease | 1 Patients |
| Cohort 6 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 8, Progressive Disease | 0 Patients |
| Cohort 6 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 4, Progressive Disease | 0 Patients |
| Cohort 6 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 2, Stable Disease | 0 Patients |
| Cohort 6 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 2, Partial Response | 0 Patients |
| Cohort 6 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 4, Unknown | 0 Patients |
| Cohort 6 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 2, Complete Response | 0 Patients |
| Cohort 6 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 8, Complete Response | 0 Patients |
| Cohort 6 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 1, Unknown | 0 Patients |
| Cohort 6 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 1, Progressive Disease | 1 Patients |
| Cohort 6 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 8, Partial Response | 0 Patients |
| Cohort 6 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 1, Stable Disease | 0 Patients |
| Cohort 6 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 8, Unknown | 0 Patients |
| Cohort 6 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 8, Stable Disease | 0 Patients |
| Cohort 6 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 1, Partial Response | 0 Patients |
| Cohort 6 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 1, Complete Response | 0 Patients |
| Cohort 6 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 4, Partial Response | 0 Patients |
| Cohort 6 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 4, Complete Response | 0 Patients |
| Cohort 6 | Number of Patients With RECIST Assessment on the Injected Lesion | Month 2, Unknown | 0 Patients |
Secondary
Number of Patients With Systemic Tumor Antigen Specific T-cell Responses
The host immune and inflammatory response to C. novyi-NT spores was measured in routine blood sampling over the course of the study. Release of T-cell cytokines and effector molecules (interferon \[IFN\]-γ , Granzyme B, and tumor necrosis factor \[TNF\]-α) from the patient's own peripheral blood mononuclear cells (PBMCs) treated with allogenic tumor cell line lysates were quantified by Enzyme-Linked Immunosorbent Spot (ELISPOT) assays. A positive response was defined as a frequency that is significantly (p \<0.05, two-tailed t-test) greater than the mean of control no-antigen wells and detectable (i.e., \>1:100,000). No patients were analyzed for Cohort 1 and Cohort 2 based on the original study protocol.
Time frame: 2 years
Population: The efficacy data set or full analysis set consisted of all patients in the safety population who had both a baseline tumor assessment and at least one post-baseline tumor assessment. Patients were included in the analysis according to the dose of IMP received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | Number of Patients With Systemic Tumor Antigen Specific T-cell Responses | 1 Patients |
| Cohort 2 | Number of Patients With Systemic Tumor Antigen Specific T-cell Responses | 2 Patients |
| Cohort 3 | Number of Patients With Systemic Tumor Antigen Specific T-cell Responses | 3 Patients |
| Cohort 4 | Number of Patients With Systemic Tumor Antigen Specific T-cell Responses | 1 Patients |
Secondary
Percentage Change in Tumor Size From Baseline of the Target Injected Lesion, Measured by Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans
To document preliminary anti-tumor activity of the injected lesion after administering a single IT injection of C. novyi-NT in humans with treatment-refractory solid tumor malignancies. Response and progression was evaluated using the international criteria proposed by the RECIST 1.1. Objective responses were measured by serial CT or MRI scans of the injected lesion and sites of metastatic involvement. Overall response, based on CT/MRI scan results, was based on observation of measurable and non-measurable disease as compared to baseline and nadir in target and non-target tumors per RECIST 1.1. Change from baseline is presented.
Time frame: At screening, at follow up (at 1, 2, 4, and 8 months (±2 days) after dosing)
Population: The efficacy data set or full analysis set consisted of all patients in the safety population who had both a baseline tumor assessment and at least one post-baseline tumor assessment. Patients were included in the analysis according to the dose of IMP received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 | Percentage Change in Tumor Size From Baseline of the Target Injected Lesion, Measured by Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans | Patient 1, Month 2 | -23.68 Percentage of change |
| Cohort 1 | Percentage Change in Tumor Size From Baseline of the Target Injected Lesion, Measured by Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans | Patient 2, Month 1 and Month 2 | 0 Percentage of change |
| Cohort 1 | Percentage Change in Tumor Size From Baseline of the Target Injected Lesion, Measured by Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans | Patient 3, Month 1 | 19.23 Percentage of change |
| Cohort 1 | Percentage Change in Tumor Size From Baseline of the Target Injected Lesion, Measured by Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans | Patient 1, Month 1 | 1.32 Percentage of change |
| Cohort 2 | Percentage Change in Tumor Size From Baseline of the Target Injected Lesion, Measured by Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans | Patient 4, Month 1 | -21.90 Percentage of change |
| Cohort 2 | Percentage Change in Tumor Size From Baseline of the Target Injected Lesion, Measured by Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans | Patient 4, Month 2 | 0 Percentage of change |
| Cohort 2 | Percentage Change in Tumor Size From Baseline of the Target Injected Lesion, Measured by Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans | Patient 5, Month 1 | 11.54 Percentage of change |
| Cohort 2 | Percentage Change in Tumor Size From Baseline of the Target Injected Lesion, Measured by Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans | Patient 6, Month 1 | 10.71 Percentage of change |
| Cohort 2 | Percentage Change in Tumor Size From Baseline of the Target Injected Lesion, Measured by Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans | Patient 6, Month 2 | 32.14 Percentage of change |
| Cohort 3 | Percentage Change in Tumor Size From Baseline of the Target Injected Lesion, Measured by Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans | Patient 7, Month 1 | NA Percentage of change |
| Cohort 3 | Percentage Change in Tumor Size From Baseline of the Target Injected Lesion, Measured by Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans | Patient 8, Month 1 | -20 Percentage of change |
| Cohort 3 | Percentage Change in Tumor Size From Baseline of the Target Injected Lesion, Measured by Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans | Patient 9, Month 1 | -1.85 Percentage of change |
| Cohort 3 | Percentage Change in Tumor Size From Baseline of the Target Injected Lesion, Measured by Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans | Patient 10, Month 1 | 6.67 Percentage of change |
| Cohort 4 | Percentage Change in Tumor Size From Baseline of the Target Injected Lesion, Measured by Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans | Patient 12, Month 2 | 1.69 Percentage of change |
| Cohort 4 | Percentage Change in Tumor Size From Baseline of the Target Injected Lesion, Measured by Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans | Patient 11, Month 1 | -2.22 Percentage of change |
| Cohort 4 | Percentage Change in Tumor Size From Baseline of the Target Injected Lesion, Measured by Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans | Patient 11, Month 2 | 15.56 Percentage of change |
| Cohort 4 | Percentage Change in Tumor Size From Baseline of the Target Injected Lesion, Measured by Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans | Patient 12, Month 1 | 13.56 Percentage of change |
| Cohort 4 | Percentage Change in Tumor Size From Baseline of the Target Injected Lesion, Measured by Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans | Patient 12, Month 4 | -13.56 Percentage of change |
| Cohort 4 | Percentage Change in Tumor Size From Baseline of the Target Injected Lesion, Measured by Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans | Patient 12, Month 8 | 13.56 Percentage of change |
| Cohort 4 | Percentage Change in Tumor Size From Baseline of the Target Injected Lesion, Measured by Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans | Patient 13, Month 1 | 26.61 Percentage of change |
| Cohort 4 | Percentage Change in Tumor Size From Baseline of the Target Injected Lesion, Measured by Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans | Patient 13, Month 2 | 42.20 Percentage of change |
| Cohort 4 | Percentage Change in Tumor Size From Baseline of the Target Injected Lesion, Measured by Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans | Patient 14, Month 1 | 14.29 Percentage of change |
| Cohort 4 | Percentage Change in Tumor Size From Baseline of the Target Injected Lesion, Measured by Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans | Patient 14, Month 2 | 14.29 Percentage of change |
| Cohort 4 | Percentage Change in Tumor Size From Baseline of the Target Injected Lesion, Measured by Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans | Patient 15, Month 1 | 16.95 Percentage of change |
| Cohort 4 | Percentage Change in Tumor Size From Baseline of the Target Injected Lesion, Measured by Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans | Patient 16, Month 1 | -11.76 Percentage of change |
| Cohort 4 | Percentage Change in Tumor Size From Baseline of the Target Injected Lesion, Measured by Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans | Patient 16, Month 2 | -14.29 Percentage of change |
| Cohort 5 | Percentage Change in Tumor Size From Baseline of the Target Injected Lesion, Measured by Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans | Patient 17, Month 1 | -7.14 Percentage of change |
| Cohort 5 | Percentage Change in Tumor Size From Baseline of the Target Injected Lesion, Measured by Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans | Patient 17, Month 2 | 0 Percentage of change |
| Cohort 5 | Percentage Change in Tumor Size From Baseline of the Target Injected Lesion, Measured by Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans | Patient 17, Month 4 | 3.57 Percentage of change |
| Cohort 5 | Percentage Change in Tumor Size From Baseline of the Target Injected Lesion, Measured by Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans | Patient 17, Month 8 | 10.71 Percentage of change |
| Cohort 5 | Percentage Change in Tumor Size From Baseline of the Target Injected Lesion, Measured by Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans | Patient 18, Month 1 | 30.23 Percentage of change |
| Cohort 5 | Percentage Change in Tumor Size From Baseline of the Target Injected Lesion, Measured by Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans | Patient 18, Month 2 | 86.05 Percentage of change |
| Cohort 5 | Percentage Change in Tumor Size From Baseline of the Target Injected Lesion, Measured by Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans | Patient 19, Month 1 | -6.67 Percentage of change |
| Cohort 5 | Percentage Change in Tumor Size From Baseline of the Target Injected Lesion, Measured by Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans | Patient 19, Month 2 | 6.67 Percentage of change |
| Cohort 5 | Percentage Change in Tumor Size From Baseline of the Target Injected Lesion, Measured by Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans | Patient 23, Month 1 | 3.13 Percentage of change |
| Cohort 5 | Percentage Change in Tumor Size From Baseline of the Target Injected Lesion, Measured by Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans | Patient 23, Month 2 | 18.75 Percentage of change |
| Cohort 5 | Percentage Change in Tumor Size From Baseline of the Target Injected Lesion, Measured by Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans | Patient 24, Month 1 | 19.30 Percentage of change |
| Cohort 5 | Percentage Change in Tumor Size From Baseline of the Target Injected Lesion, Measured by Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans | Patient 22, Month 1 | 12.20 Percentage of change |
| Cohort 5 | Percentage Change in Tumor Size From Baseline of the Target Injected Lesion, Measured by Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans | Patient 22, Month 2 | 19.51 Percentage of change |
| Cohort 6 | Percentage Change in Tumor Size From Baseline of the Target Injected Lesion, Measured by Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans | Patient 20, Month 1 | 48.24 Percentage of change |
| Cohort 6 | Percentage Change in Tumor Size From Baseline of the Target Injected Lesion, Measured by Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans | Patient 20, Month 2 | 23.53 Percentage of change |
| Cohort 6 | Percentage Change in Tumor Size From Baseline of the Target Injected Lesion, Measured by Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans | Patient 21, Month 1, Month 2, Month 4 | NA Percentage of change |
Secondary
Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT
To study the presence of circulating C. novyi-NT spores after administration as a single IT injection to humans with treatment-refractory solid tumor malignancies.
Time frame: At Screening, at Days -1 to 0, at Days 1, 2, 3, 4, 5, 7, at follow up (at 2 months (±2 days) after dosing)
Population: The safety data set included all patients who received any amount of C. novyi-NT, the IMP. Patients were included in the safety analysis according to the dose of IMP received.~Note: Two patients had positive C.novyi culture at Screening due to contamination, and one patient in Cohort 4 had positive C. novyi culture on Day 3 due to contamination.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Month 2 | 1 Patients |
| Cohort 1 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Screening | 0 Patients |
| Cohort 1 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Day -1 to Day 0 | 0 Patients |
| Cohort 1 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Day 4 | 1 Patients |
| Cohort 1 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Day 1 | 0 Patients |
| Cohort 1 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Day 3 | 1 Patients |
| Cohort 1 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Day 2 | 0 Patients |
| Cohort 1 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Day 5 | 1 Patients |
| Cohort 1 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Day 7 | 0 Patients |
| Cohort 2 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Day 3 | 0 Patients |
| Cohort 2 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Day 4 | 0 Patients |
| Cohort 2 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Day 7 | 0 Patients |
| Cohort 2 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Day -1 to Day 0 | 0 Patients |
| Cohort 2 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Screening | 1 Patients |
| Cohort 2 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Day 1 | 0 Patients |
| Cohort 2 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Day 2 | 0 Patients |
| Cohort 2 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Month 2 | 0 Patients |
| Cohort 2 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Day 5 | 0 Patients |
| Cohort 3 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Screening | 0 Patients |
| Cohort 3 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Day 4 | 0 Patients |
| Cohort 3 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Month 2 | 0 Patients |
| Cohort 3 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Day 2 | 0 Patients |
| Cohort 3 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Day 7 | 0 Patients |
| Cohort 3 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Day 3 | 0 Patients |
| Cohort 3 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Day 1 | 0 Patients |
| Cohort 3 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Day -1 to Day 0 | 0 Patients |
| Cohort 3 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Day 5 | 0 Patients |
| Cohort 4 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Day 2 | 1 Patients |
| Cohort 4 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Month 2 | 0 Patients |
| Cohort 4 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Day -1 to Day 0 | 0 Patients |
| Cohort 4 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Day 1 | 0 Patients |
| Cohort 4 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Day 7 | 0 Patients |
| Cohort 4 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Screening | 0 Patients |
| Cohort 4 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Day 3 | 1 Patients |
| Cohort 4 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Day 4 | 0 Patients |
| Cohort 4 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Day 5 | 0 Patients |
| Cohort 5 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Screening | 0 Patients |
| Cohort 5 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Day 3 | 0 Patients |
| Cohort 5 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Day 2 | 0 Patients |
| Cohort 5 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Day 1 | 1 Patients |
| Cohort 5 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Day 7 | 0 Patients |
| Cohort 5 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Day -1 to Day 0 | 1 Patients |
| Cohort 5 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Day 5 | 0 Patients |
| Cohort 5 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Month 2 | 0 Patients |
| Cohort 5 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Day 4 | 0 Patients |
| Cohort 6 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Month 2 | 0 Patients |
| Cohort 6 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Screening | 1 Patients |
| Cohort 6 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Day -1 to Day 0 | 0 Patients |
| Cohort 6 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Day 1 | 1 Patients |
| Cohort 6 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Day 2 | 0 Patients |
| Cohort 6 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Day 3 | 0 Patients |
| Cohort 6 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Day 4 | 0 Patients |
| Cohort 6 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Day 5 | 0 Patients |
| Cohort 6 | Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT | Scheduled, Day 7 | 1 Patients |