Breast Cancer, Head and Neck Cancer, Squamous Cell Carcinoma, Lymphoma, Pancreatic Cancer, Liver Cancer, Colon Cancer, Lung Cancer, Bile Duct Cancer, Chordoma of Sacrum, Sarcoma
Conditions
Keywords
Neoplasm, Malignancy, Intratumoral, Intralesional, anti-PD-1 antibodies, Immuno therapy, Dose escalation, Platinum, Intensity Therapeutics, INT230-6, Cisplatin, Vinblastine, PD-1, Vinca, KEYTRUDA®, Pembrolizumab, CTLA-4, Carcinoma, Yervoy, Ipilimumab, Keynote A10, CA184-592
Brief summary
This study evaluated the intratumoral administration of escalating doses of a novel, experimental drug, INT230-6. The study was conducted in patients with several types of refractory cancers including those at the surface of the skin (breast, squamous cell, head and neck) and tumors within the body such (pancreatic, colon, liver, lung, etc.). Sponsor also tested INT230-6 in combination with anti-PD-1 and anti-CTLA-4 antibodies.
Detailed description
INT230-6 is comprised of 3 agents in a fixed ratio - a cell permeation enhancer and two, potent anti-cancer payloads (cisplatin and vinblastine sulfate). The penetration enhancer facilitates dispersion of the two drugs throughout injected tumors and enables increased diffusion into cancer cells. Nonclinical safety studies showed no findings following drug injection into healthy tissues. Historically physicians administer the two active drugs comprising INT230-6 by intravenous (IV) infusion to achieve a systemic blood level at the limit of tolerability. The objective is destroy both visible tumors and unseen circulating cancer cells (micro-metastases). Unfortunately, dosing drugs IV delivers only a small amount with a low concentration at the tumor site. This approach especially for late stage cancers is not highly effective and often quite toxic to the patient. Attempts at direct intratumoral injection with chemotherapeutic agents have not shown the ability to treat the injected tumor, non-injected tumors or micro-metastases. This lack of efficacy for local administration is due possibly to poor dispersion and a lack of cell uptake of the agents. Due to the use of the novel cell penetration enhancing agent INT230-6 treatment demonstrated strong efficacy in animals having large tumors. The Sponsor's in vivo, non-clinical data shows that INT230-6 thoroughly saturates and kills injected tumors. In addition, the drug induces an adaptive (T-cell mediated) immune response that attacks not only the injected tumor, but non-injected tumors and unseen micro-metastases. Cured animals become permanently immunized against the type of cancer that INT230-6 eliminates. Clinical trial IT-01 sought to determine the safety and potential efficacy of dosing INT230-6 directly into several different types of cancers. In addition, animal studies showed a strong synergy of INT230-6 with immune modulation agents. Thus, as part of study IT-01 the Sponsor seeks to understand the safety and efficacy of INT230-6 when administered in combination with immuno-therapeutic agents such as antibodies that target Programmed Cell Death (PD-1 or anti-PD-1) and Cytotoxic T-Lymphocyte Associated Protein 4 (CTLA-4 or anti-CTLA-4) receptors. This study sought to understand whether tumor regression can be achieved, and patient outcomes improved.
Interventions
DRUGINT230-6
INT230-6 is clear sterile solution administered by injection directly into the tumor to be treated. The product contains a cell permeation agent with cisplatin and vinblastine sulfate at fixed concentrations.
BIOLOGICALanti-PD-1 antibody
The anti-PD-1 antibody will be added concomitantly with INT230-6 as noted in cohort DEC and DEC2
BIOLOGICALanti-CTLA-4 antibody
The anti-CTLA-4 antibody will be added concomitantly with INT230-6 as noted in cohort FEC
Sponsors
Merck Sharp & Dohme LLC
Bristol-Myers Squibb
Intensity Therapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Masking description
There were no masking and all patients received INT230-6 treatments.
Intervention model description
There were 6 cohorts in the escalation portion of the protocol. Five dosed INT230-6 alone and one was combined with pembrolizumab. Cohorts A and B1 treated superficial tumors at a 1:4 ratio of drug to tumor with a low tumor load once per month. Cohort EA was similar to cohort A with INT230-6 every 2 weeks. Cohort EC escalated the total and maximal dose per any one tumor to a ratio of 1:2 & dosed every two weeks. Cohort EC2 explored a drug load ratio of 1:3 and escalated the dose per tumor further. Cohort DEC combined INT230-6 with a fixed amount of pembrolizumab. Completed, non-escalation cohorts include 1) monotherapy INT230-6 cohort (EC3) dosed every two weeks 2) INT230-6 in a combination with pembrolizumab (DEC2) and 3) INT230-6 in combination with ipilimumab (FEC). Other specific regimens or combinations of INT230-6 may be designated by the Study Steering Committee.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
INT230-6 monotherapy Cohorts EC2 and EC3, combination with KEYTRUDA® cohort DEC2 and combination with Yervoy cohort FEC. Where criteria diverge the DEC2 and FEC specific criteria will be noted. 1. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial. 2. Men and Women \> 18 years of age on the day of signing consent. 3. Have an Eastern Cooperative Oncology Group (ECOG) performance status \< 2; (for pembrolizumab and ipilimumab combinations please see supplements DEC/DEC2 and FEC for ECOG criteria). 4. Populations: INT230-6 will be injected into deep or superficial tumors for subjects with histologically or cytologically confirmed advanced or metastatic cancers; (for pembrolizumab and ipilimumab combinations please see supplements DEC/DEC2 and FEC for Populations). 5. Includes subjects with loco-regional disease that have relapsed/recurred within 6 months of chemo-radiation and who have no standard of care. 6. Subjects with metastatic disease who have failed one or more approved standard therapies, or have no alternate approved therapy available. Failure of all approved therapies that have a modest or marginal impact on survival is not required as long as the treating physician believes that treatment on study is appropriate for the subject and documents that the subject elects to defer the approved therapies. Note: There is no limit on the number of prior therapies that a patient (subject) may have received prior to enrollment in any cohort. 7. Subjects must have measurable disease by iRECIST 1.1 criteria including one target tumor for injection by the local site investigator/radiology. Superficial tumors must have one tumor greater than or equal to 1.0 cm, deep tumors greater than or equal to 1.0 cm (as measured by caliper (for non-injected tumors only) or image guidance). Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. 8. Subjects must have a minimum of one injectable lesion as determined by the investigator (for superficial tumors) or radiologist (deep tumors). 9. Prior chemotherapy or immunotherapy (tumor vaccine, cytokine, or growth factor given to control the cancer: systemic or IT) must have been completed at least 4 weeks prior to dosing (with the exception of kinase inhibitors or other short half-life drugs, a 2 week washout is acceptable prior to treatment) and all adverse events have either returned to baseline or stabilized. Note: Subjects who have received prior platinum therapy are eligible irrespective of their response. 10. Prior systemic radiation therapy (either IV, intrahepatic or oral) completed at least 4 weeks prior to study drug administration; (for ipilimumab combination please see supplement FEC
Exclusion criteria
). 11. Prior focal radiotherapy completed at least 2 weeks prior to study drug administration. 12. Prior major treatment-related surgery completed at least 4 weeks prior to study drug administration. 13. No prior primary or metastatic brain or meningeal tumors unless clinically and radiographically stable as well as off steroid therapy for at least 2 months. 14. Life expectancy ≥8 weeks; (for ipilimumab combination please see supplement FEC inclusion criteria). 15. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: 1. Not a woman of childbearing potential (WOCBP) 2. A WOCBP subject who may become pregnant or who are sexually active with a partner and who could become pregnant agrees to use an effective form of barrier contraception during the study and for at least 180 days in monotherapy; (for pembrolizumab and ipilimumab combinations please see supplements DEC/DEC2 and FEC for pregnancy criteria). (Male subjects must agree to use contraception and refrain from sperm donation during the study for 180 days after administration of study drug.) 16. Have adequate organ function as defined by the below screening laboratory values that must meet the following criteria: 1. WBC ≥2000/μL (≥2 x 109/L). 2. Neutrophils ≥1000/μL (≥1 x 109/L); (for pembrolizumab and ipilimumab combinations please see supplements DEC/DEC2 and FEC for neutrophil criteria). 3. For subjects with planned superficial only injections: PT, PTT/aPTT, and INR ≤1.5 × ULN, Platelets ≥70x103/μL (≥ 70 x 109/L), Hemoglobin ≥8 g/dL 4. Creatinine within the institution's laboratory upper limit of normal or calculated creatinine clearance \>50 ml/min; (for pembrolizumab combination please see supplements DEC/DEC2 for creatine criteria). 5. ALT (SGOT)/AST (SGPT) ≤2.5 x ULN without, and ≤ 5 x ULN with hepatic metastases. 6. Bilirubin ≤2 x ULN (except subjects with Gilbert's syndrome, who must have total bilirubin \<3.0 mg/dL (\<52 µmol/L); (for pembrolizumab and ipilimumab combinations please see supplements DEC/DEC2 and FEC for bilirubin criteria). 7. For subjects with planned deep tumor injections: PT, PTT/aPPT, and INR within normal limits; Platelet count ≥100,000/μL; hemoglobin ≥ 9 g/dL. Note: ALT (SGPT) =alanine aminotransferase (serum glutamic pyruvic transaminase); AST (SGOT) =aspartate aminotransferase (serum glutamic oxaloacetic transaminase); ULN=upper limit of normal. 1 Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks. 17. Additional criteria for combination arms can be found in the appropriate combination protocol supplements. Refer to the Investigative site for details. Additional Inclusion Criteria for DEC2 cohort (anti-PD1 combination, KEYTRUDA® (pembrolizumab)) Population: Subjects with histologically or cytologically confirmed advanced or metastatic Pancreatic, Cholangiocarcinoma, non-MSI-H and/or MMR proficient colorectal cancer, and Squamous Cell Carcinoma tumors. Additional Inclusion Criteria for FEC cohort (anti-CTLA-4 combination, Yervoy (ipilimumab)) Population: Subjects with histologically or cytologically confirmed advanced or metastatic Hepatocellular carcinoma (HCC), breast cancer regardless of histology (BC) or soft tissue sarcoma NOTE: DEC and FEC combination cohorts have additional Inclusion Criteria - refer to the Investigative site for details.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate and Severity of Treatment-emergent Adverse Events ≥ Grade 3 Attributed to Study Drug Using the NCI Common Terminology Criteria for Adverse Events (CTCAE v.4.03) (Scale 1 to 5) | Up to 5 years | The primary objective is to assess the safety and tolerability of single and multiple intratumoral doses of INT230-6 in subjects with advanced or recurrent malignancies. This will be assessed by the rate of ≥ grade 3 AE's attributed to INT230-6 and not the underlying disease. NCI Common Terminology Criteria for Adverse Events (CTCAE v.4.03) (Scale 1 (least severe) to 5 (most severe)) All recorded adverse events will be listed and tabulated by system organ class, preferred term, and dose and coded according to the most current version of MedDRA. The incidence of adverse events will be tabulated and reviewed for potential significance and clinical importance. Adverse Events will be summarized for all reported data and by study period: a) up to and including 28 days post last dose of initial treatment, and b) from first dose of re-initiation of treatment, for subjects who re-initiate study therapy while in follow-up, up to 28 days post-dose of the last re-treatment dose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Determine Pharmacokinetic Parameter Peak Plasma (Cmax in ng/mL) of Each of the 3 Main Components of INT230-6. | T = 1 hour after first dose | Characterize the peak plasma profile for the three INT230-6 components after single and then multiple IT tumor site injections for safety purposes. Timepoints for sample collection were T = 1 Hours after dosing. Mean dose volume categories that were used to summarize data were as follows: 2 mL (range 0 to 3.5 mL) 5 mL (range 3.6 to 6 mL) 10 mL (range \>6 to 12 mL) 17 mL (range \>12 to 24 mL) 30 mL (range \>24 mL to 44 mL) 68 mL (range \>44 to 98 mL) 118 mL (range \>98 to 175 mL) |
| Preliminary Efficacy: Assess the Preliminary Efficacy of INT230-6 by Measuring the Disease Control Rate (DCR) Based on the Response Evaluation Criteria in Solid Tumors (RECIST) and Immune RECIST (iRECIST) Criteria, | Up to 5 years | Assess the preliminary efficacy of INT230-6 by measuring the disease control rate (CR+PR+SD) as assessed by iRECIST. Complete response (CR) and partial response (PR) will be defined for injected tumors followed per RECIST 1.1 utilizing target lesions. Progressive disease will be determined by clinical or radiological deterioration leading to the subject being taken off-treatment at the discretion of the investigator. Stable disease (SD) is defined as any adequate assessment not considered CR, PR, or progression. |
| Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | T= 0, 1, 3, 6, 24 Hours after dosing | Characterize the pharmacokinetic AUC profile of each of the three INT230-6 components for AUC after single IT tumor site injection for safety purposes. Timepoints for sample collection were T = 0, 1, 3, 6, 24 Hours after dosing. Mean dose volume categories that were used to summarize data were as follows: 2 mL (range 0 to 3.5 mL) 5 mL (range 3.6 to 6 mL) 10 mL (range \>6 to 12 mL) 17 mL (range \>12 to 24 mL) 30 mL (range \>24 mL to 44 mL) 68 mL (range \>44 to 98 mL) 118 mL (range \>98 to 175 mL) |
| Key Pharmacokinetic Parameters, Half Live (Hours) of Each of the 3 Main Components of INT230-6. | T= 0, 1, 3, 6, 24 hours | Characterize the half life of each of the three INT230-6 components after single and multiple IT tumor site injections for safety purposes. Timepoints for sample collection were T = 0, 1, 3, 6, 24 Hours after dosing. Mean dose volume categories that were used to summarize data were as follows: 2 mL (range 0 to 3.5 mL) 5 mL (range 3.6 to 6 mL) 10 mL (range \>6 to 12 mL) 17 mL (range \>12 to 24 mL) 30 mL (range \>24 mL to 44 mL) 68 mL (range \>44 to 98 mL) 118 mL (range \>98 to 175 mL) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory: Overall Subject Outcome | Up to 3 years | Evaluate overall response by iRECIST including survival |
| Exploratory: Blood, Genetic and Tissue Biomarker Identification From Cell Flow Phenotyping, Tissue Analysis, Genetic SNP Analysis. | Up to 2 months | Evaluate various tumor and anti-tumor immune response biomarkers from blood, tumor tissue that may correlate with tumor response. Flow and tissue panels may include Live-Dead, CD3, CD4, CD8, FoxP3, Ki-67, ICOS, DAPI, PD-1, LAG-3, TIM-3, CTLA-4 and analysis of blood serum cytokine such as Th1/Th2, IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12 p70, IL-13, and TNF-α. |
| Exploratory: Control or Regression of Non Injected Tumors by Measurement of Length (in Centimeters) Radio-graphically Using Computer Tomography or Magnetic Resonance Imaging. | Up to 18 months | Characterize response in non-injected lesions (up to 5) using length (cm) as the key parameter for measurement. |
Countries
Canada, United States
Participant flow
Pre-assignment details
One Subject (IT-004-016) had been enrolled in the study but deteriorated before the first dose was administered. The subject was originally planned to be placed in Cohort DEC2. This discontinuation means 110 patients were treated.
Participants by arm
| Arm | Count |
|---|---|
| Monotherapy: (Cohort A1) A1:INT230-6 injections every 28 days for 5 sessions into only superficial tumors, low starting dose, low concentration per tumor. | 6 |
| Monotherapy: (Cohort B1) B1:INT230-6 injections every 28 days for 5 sessions into deep tumors, low starting dose, low drug concentration per tumor Completed Cohort | 4 |
| Monotherapy: (Cohort E-A) EA:INT230-6 injections every 2 weeks for 5 sessions into superficial tumors, medium starting dose, low drug concentration per tumor Completed Cohort | 4 |
| Monotherapy: (Cohort E-C) EC:INT230-6 injections every 2 weeks for 5 sessions into superficial or deep tumors, moderately high starting dose, high drug concentration per tumor Completed Cohort | 21 |
| Monotherapy: (Cohort EC-2) EC2:INT230-6 injections every 2 weeks for 5 sessions into superficial or deep tumors, high starting dose, moderate drug concentration per tumor, higher number of tumors to be treated per session than EC. | 20 |
| Monotherapy: (Cohort EC3) EC3:INT230-6 injections every 2 weeks for 5 sessions at fixed maximal dose into superficial or deep tumors, unlimited number of tumors to be treated per session with retreatment once every 9 weeks for two years. Completed Cohort | 9 |
| INT 230-6 Combined With Pembrolizumab (Cohort DEC) DEC: INT230-6 injections every 2 weeks for 5 sessions with the possibility for INT230-6 retreatment into superficial tumors, with addition of anti-PD-1 antibody Keytruda (pembrolizumab) dosed concurrently starting at Day 1 every 3 weeks for two years for selected cancer types. | 6 |
| INT 230-6 Combined With Pembrolizumab (Cohort DEC2) DEC2:INT230-6 per the dosing of cohort EC3 combined with Keytruda (pembrolizumab) dosed per DEC concurrently starting at Day 1 for selected cancers. | 22 |
| INT 230-6 Combined With Ipilimumab (Cohort FEC) FEC: INT230-6 per the EC3 regimen combined with Yervoy (ipilimumab) dosed concurrently starting at Day 1 every 3 weeks for four treatments for selected cancer types.
Completed Cohort anti-CTLA-4 antibody: The anti-CTLA-4 antibody will be added concomitantly with INT230-6 as noted in cohort FEC. | 18 |
| Total | 110 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 | 1 | 3 | 1 | 0 | 1 | 3 | 0 |
| Overall Study | Clinical Deterioration | 2 | 0 | 0 | 2 | 1 | 1 | 0 | 3 | 2 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Physician Decision | 1 | 0 | 0 | 2 | 1 | 0 | 2 | 3 | 0 |
| Overall Study | Radiographic Deterioration | 0 | 3 | 1 | 2 | 6 | 3 | 0 | 4 | 2 |
| Overall Study | Rapid Progression of Disease | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Refused Further Treatment | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 2 | 0 | 2 | 0 | 4 | 1 |
Baseline characteristics
| Characteristic | Monotherapy: (Cohort B1) | Monotherapy: (Cohort E-A) | Monotherapy: (Cohort A1) | Monotherapy: (Cohort E-C) | Monotherapy: (Cohort EC-2) | Monotherapy: (Cohort EC3) | INT 230-6 Combined With Pembrolizumab (Cohort DEC) | INT 230-6 Combined With Pembrolizumab (Cohort DEC2) | INT 230-6 Combined With Ipilimumab (Cohort FEC) | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 0 Participants | 1 Participants | 7 Participants | 11 Participants | 4 Participants | 2 Participants | 14 Participants | 6 Participants | 47 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 4 Participants | 5 Participants | 14 Participants | 9 Participants | 5 Participants | 4 Participants | 8 Participants | 12 Participants | 63 Participants |
| Age, Continuous | 61.5 years STANDARD_DEVIATION 7.9 | 57.6 years STANDARD_DEVIATION 4.1 | 54.5 years STANDARD_DEVIATION 7.1 | 59.0 years STANDARD_DEVIATION 9.9 | 64.6 years STANDARD_DEVIATION 9.4 | 61.5 years STANDARD_DEVIATION 11.3 | 64.2 years STANDARD_DEVIATION 16 | 68.4 years STANDARD_DEVIATION 7.3 | 64.2 years STANDARD_DEVIATION 11.1 | 62.9 years STANDARD_DEVIATION 9.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 2 Participants | 2 Participants | 0 Participants | 3 Participants | 3 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 3 Participants | 6 Participants | 19 Participants | 18 Participants | 7 Participants | 6 Participants | 19 Participants | 15 Participants | 97 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 3 Participants | 2 Participants | 2 Participants | 1 Participants | 5 Participants | 1 Participants | 15 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) White | 3 Participants | 4 Participants | 5 Participants | 16 Participants | 18 Participants | 5 Participants | 5 Participants | 13 Participants | 13 Participants | 82 Participants |
| Region of Enrollment Canada | 0 participants | 0 participants | 3 participants | 1 participants | 1 participants | 0 participants | 4 participants | 1 participants | 1 participants | 11 participants |
| Region of Enrollment United States | 4 participants | 4 participants | 3 participants | 20 participants | 19 participants | 9 participants | 2 participants | 21 participants | 17 participants | 99 participants |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 4 Participants | 11 Participants | 7 Participants | 6 Participants | 3 Participants | 8 Participants | 10 Participants | 54 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 2 Participants | 10 Participants | 13 Participants | 3 Participants | 3 Participants | 14 Participants | 8 Participants | 56 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 | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 4 | 0 / 4 | 0 / 21 | 0 / 20 | 0 / 9 | 0 / 8 | 0 / 22 | 0 / 18 |
| other Total, other adverse events | 4 / 6 | 2 / 4 | 3 / 4 | 20 / 21 | 20 / 20 | 7 / 9 | 7 / 8 | 19 / 22 | 16 / 18 |
| serious Total, serious adverse events | 0 / 6 | 0 / 4 | 0 / 4 | 1 / 21 | 1 / 20 | 1 / 9 | 2 / 8 | 2 / 22 | 1 / 18 |
Outcome results
Primary
Rate and Severity of Treatment-emergent Adverse Events ≥ Grade 3 Attributed to Study Drug Using the NCI Common Terminology Criteria for Adverse Events (CTCAE v.4.03) (Scale 1 to 5)
The primary objective is to assess the safety and tolerability of single and multiple intratumoral doses of INT230-6 in subjects with advanced or recurrent malignancies. This will be assessed by the rate of ≥ grade 3 AE's attributed to INT230-6 and not the underlying disease. NCI Common Terminology Criteria for Adverse Events (CTCAE v.4.03) (Scale 1 (least severe) to 5 (most severe)) All recorded adverse events will be listed and tabulated by system organ class, preferred term, and dose and coded according to the most current version of MedDRA. The incidence of adverse events will be tabulated and reviewed for potential significance and clinical importance. Adverse Events will be summarized for all reported data and by study period: a) up to and including 28 days post last dose of initial treatment, and b) from first dose of re-initiation of treatment, for subjects who re-initiate study therapy while in follow-up, up to 28 days post-dose of the last re-treatment dose.
Time frame: Up to 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Monotherapy: Cohort A1 | Rate and Severity of Treatment-emergent Adverse Events ≥ Grade 3 Attributed to Study Drug Using the NCI Common Terminology Criteria for Adverse Events (CTCAE v.4.03) (Scale 1 to 5) | 0 Participants |
| Monotherapy: Cohort B1 | Rate and Severity of Treatment-emergent Adverse Events ≥ Grade 3 Attributed to Study Drug Using the NCI Common Terminology Criteria for Adverse Events (CTCAE v.4.03) (Scale 1 to 5) | 0 Participants |
| Monotherapy: Cohort EA | Rate and Severity of Treatment-emergent Adverse Events ≥ Grade 3 Attributed to Study Drug Using the NCI Common Terminology Criteria for Adverse Events (CTCAE v.4.03) (Scale 1 to 5) | 1 Participants |
| Monotherapy: Cohort EC | Rate and Severity of Treatment-emergent Adverse Events ≥ Grade 3 Attributed to Study Drug Using the NCI Common Terminology Criteria for Adverse Events (CTCAE v.4.03) (Scale 1 to 5) | 2 Participants |
| Monotherapy: Cohort EC-2 | Rate and Severity of Treatment-emergent Adverse Events ≥ Grade 3 Attributed to Study Drug Using the NCI Common Terminology Criteria for Adverse Events (CTCAE v.4.03) (Scale 1 to 5) | 4 Participants |
| Monotherapy: Cohort EC3 | Rate and Severity of Treatment-emergent Adverse Events ≥ Grade 3 Attributed to Study Drug Using the NCI Common Terminology Criteria for Adverse Events (CTCAE v.4.03) (Scale 1 to 5) | 0 Participants |
| INT 230-6 Combined With Pembrolizumab (Cohort DEC) | Rate and Severity of Treatment-emergent Adverse Events ≥ Grade 3 Attributed to Study Drug Using the NCI Common Terminology Criteria for Adverse Events (CTCAE v.4.03) (Scale 1 to 5) | 1 Participants |
| INT 230-6 Combined With Pembrolizumab (Cohort DEC2) | Rate and Severity of Treatment-emergent Adverse Events ≥ Grade 3 Attributed to Study Drug Using the NCI Common Terminology Criteria for Adverse Events (CTCAE v.4.03) (Scale 1 to 5) | 6 Participants |
| INT 230-6 Combined With Ipilimumab (Cohort FEC) | Rate and Severity of Treatment-emergent Adverse Events ≥ Grade 3 Attributed to Study Drug Using the NCI Common Terminology Criteria for Adverse Events (CTCAE v.4.03) (Scale 1 to 5) | 2 Participants |
Secondary
Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6.
Characterize the pharmacokinetic AUC profile of each of the three INT230-6 components for AUC after single IT tumor site injection for safety purposes. Timepoints for sample collection were T = 0, 1, 3, 6, 24 Hours after dosing. Mean dose volume categories that were used to summarize data were as follows: 2 mL (range 0 to 3.5 mL) 5 mL (range 3.6 to 6 mL) 10 mL (range \>6 to 12 mL) 17 mL (range \>12 to 24 mL) 30 mL (range \>24 mL to 44 mL) 68 mL (range \>44 to 98 mL) 118 mL (range \>98 to 175 mL)
Time frame: T= 0, 1, 3, 6, 24 Hours after dosing
Population: The pharmacokinetic (PK) analysis aggregated subjects into groups by the dose given per convention according to our SAP and PK plan. Characterization of Patients who received similar doses (2mL, 5mL, 10mL, 18 mL, 30 mL, 68 mL, 118 mL, etc.) from all the cohorts were aggregated per the plan. This methodology of grouping (as described in the PK report produces meaningful API and excipient blood concentration profiles and determines conventional PK parameters for those agents.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Monotherapy: Cohort A1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 30mL Timepoint: 24 Hours | 295.42 ng/mL | Standard Deviation 137.46 |
| Monotherapy: Cohort A1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 10mL Timepoint: 3 Hours | 114.7 ng/mL | Standard Deviation 53.38 |
| Monotherapy: Cohort A1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 118mL Timepoint: 6 Hours | 779.67 ng/mL | Standard Deviation 360.88 |
| Monotherapy: Cohort A1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 30mL Timepoint: 6 Hours | 325.73 ng/mL | Standard Deviation 152.91 |
| Monotherapy: Cohort A1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 10mL Timepoint: 6 Hours | 111.57 ng/mL | Standard Deviation 49.37 |
| Monotherapy: Cohort A1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 2mL Time point: 0 Hours | 6.38 ng/mL | Standard Deviation 20.18 |
| Monotherapy: Cohort A1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 30mL Timepoint: 3 Hours | 344.82 ng/mL | Standard Deviation 163.12 |
| Monotherapy: Cohort A1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 10mL Timepoint: 24 Hours | 100.98 ng/mL | Standard Deviation 52.36 |
| Monotherapy: Cohort A1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 5mL Timepoint: 0 Hours | 1.56 ng/mL | Standard Deviation 4.67 |
| Monotherapy: Cohort A1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 30mL Timepoint: 1 Hours | 456.47 ng/mL | Standard Deviation 195.02 |
| Monotherapy: Cohort A1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 17mL Timepoint: 0 Hours | 4.99 ng/mL | Standard Deviation 19.5 |
| Monotherapy: Cohort A1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 2mL Timepoint: 3 Hours | 28.09 ng/mL | Standard Deviation 23.16 |
| Monotherapy: Cohort A1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 30mL Timepoint: 0 Hours | 7.15 ng/mL | Standard Deviation 19.24 |
| Monotherapy: Cohort A1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 17mL Timepoint: 1 Hours | 233.15 ng/mL | Standard Deviation 125.77 |
| Monotherapy: Cohort A1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 118mL Timepoint: 0 Hours | 0 ng/mL | Standard Deviation 0 |
| Monotherapy: Cohort A1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 17mL Timepoint:24 Hours | 163.87 ng/mL | Standard Deviation 90.19 |
| Monotherapy: Cohort A1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 17mL Timepoint: 3 Hours | 187.08 ng/mL | Standard Deviation 93.22 |
| Monotherapy: Cohort A1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 5mL Timepoint: 1 Hour(s) | 77.81 ng/mL | Standard Deviation 38.16 |
| Monotherapy: Cohort A1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 17mL Timepoint: 6 Hours | 176.45 ng/mL | Standard Deviation 90.26 |
| Monotherapy: Cohort A1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 2mL Time point: 1 Hour(s) | 33.78 ng/mL | Standard Deviation 24.92 |
| Monotherapy: Cohort A1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 68mL Timepoint: 24 Hours | 610.08 ng/mL | Standard Deviation 264.39 |
| Monotherapy: Cohort A1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 5mL Timepoint: 3 Hours | 58.50 ng/mL | Standard Deviation 30.57 |
| Monotherapy: Cohort A1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 118mL Timepoint: 3 Hours | 875 ng/mL | Standard Deviation 433.39 |
| Monotherapy: Cohort A1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 68mL Timepoint: 6 Hours | 775.00 ng/mL | Standard Deviation 581.44 |
| Monotherapy: Cohort A1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 5mL Timepoint: 6 Hours | 59.04 ng/mL | Standard Deviation 32.03 |
| Monotherapy: Cohort A1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 2mL Timepoint: 6 Hours | 25.35 ng/mL | Standard Deviation 20.35 |
| Monotherapy: Cohort A1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 68mL Timepoint: 3 Hours | 741.92 ng/mL | Standard Deviation 343.37 |
| Monotherapy: Cohort A1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 5mL Timepoint: 24 Hours | 53.87 ng/mL | Standard Deviation 29.07 |
| Monotherapy: Cohort A1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 118mL Timepoint: 24 Hours | 945.33 ng/mL | Standard Deviation 544.78 |
| Monotherapy: Cohort A1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 68mL Timepoint: 1 Hours | 832.92 ng/mL | Standard Deviation 192.93 |
| Monotherapy: Cohort A1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 10mL Timepoint: 0 Hours | 4.95 ng/mL | Standard Deviation 13.09 |
| Monotherapy: Cohort A1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 118mL Timepoint: 1 Hours | 1664 ng/mL | Standard Deviation 1287.53 |
| Monotherapy: Cohort A1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 68mL Timepoint: 0 Hours | 62.93 ng/mL | Standard Deviation 222.7 |
| Monotherapy: Cohort A1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 10mL Timepoint: 1 Hour(s) | 152.63 ng/mL | Standard Deviation 67.36 |
| Monotherapy: Cohort A1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 2mL Timepoint: 24 Hours | 20.74 ng/mL | Standard Deviation 17.22 |
| Monotherapy: Cohort B1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 118mL Timepoint: 0 Hours | 0 ng/mL | Standard Deviation 0 |
| Monotherapy: Cohort B1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 2mL Time point: 0 Hours | 0 ng/mL | Standard Deviation 0 |
| Monotherapy: Cohort B1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 2mL Time point: 1 Hour(s) | 59.94 ng/mL | Standard Deviation 69.95 |
| Monotherapy: Cohort B1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 2mL Timepoint: 3 Hours | 3.33 ng/mL | Standard Deviation 6.99 |
| Monotherapy: Cohort B1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 2mL Timepoint: 6 Hours | 0 ng/mL | Standard Deviation 0 |
| Monotherapy: Cohort B1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 2mL Timepoint: 24 Hours | 0 ng/mL | Standard Deviation 0 |
| Monotherapy: Cohort B1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 5mL Timepoint: 0 Hours | 0 ng/mL | Standard Deviation 0 |
| Monotherapy: Cohort B1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 5mL Timepoint: 1 Hour(s) | 113.74 ng/mL | Standard Deviation 83.23 |
| Monotherapy: Cohort B1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 5mL Timepoint: 3 Hours | 11.43 ng/mL | Standard Deviation 15.52 |
| Monotherapy: Cohort B1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 5mL Timepoint: 6 Hours | 2.18 ng/mL | Standard Deviation 6.15 |
| Monotherapy: Cohort B1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 5mL Timepoint: 24 Hours | 0 ng/mL | Standard Deviation 0 |
| Monotherapy: Cohort B1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 10mL Timepoint: 0 Hours | 0 ng/mL | Standard Deviation 0 |
| Monotherapy: Cohort B1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 10mL Timepoint: 1 Hour(s) | 300.56 ng/mL | Standard Deviation 172.62 |
| Monotherapy: Cohort B1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 10mL Timepoint: 3 Hours | 36.68 ng/mL | Standard Deviation 51.13 |
| Monotherapy: Cohort B1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 10mL Timepoint: 6 Hours | 6.21 ng/mL | Standard Deviation 15.22 |
| Monotherapy: Cohort B1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 10mL Timepoint: 24 Hours | 0 ng/mL | Standard Deviation 0 |
| Monotherapy: Cohort B1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 17mL Timepoint: 0 Hours | 0 ng/mL | Standard Deviation 0 |
| Monotherapy: Cohort B1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 17mL Timepoint: 1 Hours | 426.75 ng/mL | Standard Deviation 306.59 |
| Monotherapy: Cohort B1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 17mL Timepoint: 3 Hours | 59.76 ng/mL | Standard Deviation 45.33 |
| Monotherapy: Cohort B1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 17mL Timepoint: 6 Hours | 19.49 ng/mL | Standard Deviation 19.77 |
| Monotherapy: Cohort B1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 17mL Timepoint:24 Hours | .5 ng/mL | Standard Deviation 2.27 |
| Monotherapy: Cohort B1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 30mL Timepoint: 0 Hours | 0.0 ng/mL | Standard Deviation 0 |
| Monotherapy: Cohort B1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 30mL Timepoint: 1 Hours | 911.55 ng/mL | Standard Deviation 790.14 |
| Monotherapy: Cohort B1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 30mL Timepoint: 3 Hours | 95.67 ng/mL | Standard Deviation 64.38 |
| Monotherapy: Cohort B1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 30mL Timepoint: 6 Hours | 26.95 ng/mL | Standard Deviation 20.34 |
| Monotherapy: Cohort B1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 30mL Timepoint: 24 Hours | .78 ng/mL | Standard Deviation 3.2 |
| Monotherapy: Cohort B1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 68mL Timepoint: 0 Hours | 289.23 ng/mL | Standard Deviation 1042.84 |
| Monotherapy: Cohort B1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 68mL Timepoint: 1 Hours | 1286.00 ng/mL | Standard Deviation 1039.43 |
| Monotherapy: Cohort B1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 68mL Timepoint: 3 Hours | 240.82 ng/mL | Standard Deviation 276.13 |
| Monotherapy: Cohort B1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 68mL Timepoint: 6 Hours | 96.54 ng/mL | Standard Deviation 146.88 |
| Monotherapy: Cohort B1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 68mL Timepoint: 24 Hours | 2.71 ng/mL | Standard Deviation 6.44 |
| Monotherapy: Cohort B1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 118mL Timepoint: 1 Hours | 2719.75 ng/mL | Standard Deviation 1848.17 |
| Monotherapy: Cohort B1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 118mL Timepoint: 3 Hours | 459.67 ng/mL | Standard Deviation 289.46 |
| Monotherapy: Cohort B1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 118mL Timepoint: 6 Hours | 183.43 ng/mL | Standard Deviation 99.64 |
| Monotherapy: Cohort B1 | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 118mL Timepoint: 24 Hours | 21.93 ng/mL | Standard Deviation 24.84 |
| Monotherapy: Cohort EA | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 118mL Timepoint: 6 Hours | 3.08 ng/mL | Standard Deviation 0.85 |
| Monotherapy: Cohort EA | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 30mL Timepoint: 6 Hours | 1.06 ng/mL | Standard Deviation 0.58 |
| Monotherapy: Cohort EA | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 10mL Timepoint: 1 Hour(s) | .74 ng/mL | Standard Deviation 0.35 |
| Monotherapy: Cohort EA | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 118mL Timepoint: 1 Hours | 9.52 ng/mL | Standard Deviation 4.52 |
| Monotherapy: Cohort EA | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 30mL Timepoint: 24 Hours | .47 ng/mL | Standard Deviation 0.38 |
| Monotherapy: Cohort EA | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 10mL Timepoint: 0 Hours | 0 ng/mL | Standard Deviation 0 |
| Monotherapy: Cohort EA | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 2mL Timepoint: 3 Hours | .04 ng/mL | Standard Deviation 0.12 |
| Monotherapy: Cohort EA | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 68mL Timepoint: 0 Hours | .44 ng/mL | Standard Deviation 1.58 |
| Monotherapy: Cohort EA | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 5mL Timepoint: 24 Hours | 0 ng/mL | Standard Deviation 0 |
| Monotherapy: Cohort EA | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 2mL Time point: 0 Hours | .33 ng/mL | Standard Deviation 1.05 |
| Monotherapy: Cohort EA | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 68mL Timepoint: 1 Hours | 5.53 ng/mL | Standard Deviation 2.35 |
| Monotherapy: Cohort EA | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 5mL Timepoint: 6 Hours | 0 ng/mL | Standard Deviation 0 |
| Monotherapy: Cohort EA | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 118mL Timepoint: 3 Hours | 4.33 ng/mL | Standard Deviation 1.46 |
| Monotherapy: Cohort EA | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 68mL Timepoint: 3 Hours | 2.73 ng/mL | Standard Deviation 0.72 |
| Monotherapy: Cohort EA | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 5mL Timepoint: 3 Hours | .16 ng/mL | Standard Deviation 0.16 |
| Monotherapy: Cohort EA | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 2mL Time point: 1 Hour(s) | .08 ng/mL | Standard Deviation 0.16 |
| Monotherapy: Cohort EA | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 68mL Timepoint: 6 Hours | 1.94 ng/mL | Standard Deviation 0.55 |
| Monotherapy: Cohort EA | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 5mL Timepoint: 1 Hour(s) | .65 ng/mL | Standard Deviation 0.76 |
| Monotherapy: Cohort EA | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 118mL Timepoint: 24 Hours | 1.24 ng/mL | Standard Deviation 1.19 |
| Monotherapy: Cohort EA | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 17mL Timepoint: 3 Hours | .66 ng/mL | Standard Deviation 0.35 |
| Monotherapy: Cohort EA | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 68mL Timepoint: 24 Hours | .94 ng/mL | Standard Deviation 0.43 |
| Monotherapy: Cohort EA | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 17mL Timepoint: 6 Hours | .51 ng/mL | Standard Deviation 0.29 |
| Monotherapy: Cohort EA | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 17mL Timepoint: 1 Hours | 1.2 ng/mL | Standard Deviation 0.72 |
| Monotherapy: Cohort EA | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 5mL Timepoint: 0 Hours | 0 ng/mL | Standard Deviation 0 |
| Monotherapy: Cohort EA | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 17mL Timepoint:24 Hours | .17 ng/mL | Standard Deviation 0.24 |
| Monotherapy: Cohort EA | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 17mL Timepoint: 0 Hours | .01 ng/mL | Standard Deviation 0.06 |
| Monotherapy: Cohort EA | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 2mL Timepoint: 24 Hours | 0 ng/mL | Standard Deviation 0 |
| Monotherapy: Cohort EA | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 30mL Timepoint: 0 Hours | 0 ng/mL | Standard Deviation 0 |
| Monotherapy: Cohort EA | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 10mL Timepoint: 24 Hours | .05 ng/mL | Standard Deviation 0.12 |
| Monotherapy: Cohort EA | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 118mL Timepoint: 0 Hours | .08 ng/mL | Standard Deviation 0.17 |
| Monotherapy: Cohort EA | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 30mL Timepoint: 1 Hours | 3.16 ng/mL | Standard Deviation 1.99 |
| Monotherapy: Cohort EA | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 10mL Timepoint: 6 Hours | .34 ng/mL | Standard Deviation 0.1 |
| Monotherapy: Cohort EA | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 2mL Timepoint: 6 Hours | 0 ng/mL | Standard Deviation 0 |
| Monotherapy: Cohort EA | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 30mL Timepoint: 3 Hours | 1.44 ng/mL | Standard Deviation 0.77 |
| Monotherapy: Cohort EA | Determine Key Pharmacokinetic Parameter, Area Under the Curve (AUC) (ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 10mL Timepoint: 3 Hours | .39 ng/mL | Standard Deviation 0.22 |
Secondary
Determine Pharmacokinetic Parameter Peak Plasma (Cmax in ng/mL) of Each of the 3 Main Components of INT230-6.
Characterize the peak plasma profile for the three INT230-6 components after single and then multiple IT tumor site injections for safety purposes. Timepoints for sample collection were T = 1 Hours after dosing. Mean dose volume categories that were used to summarize data were as follows: 2 mL (range 0 to 3.5 mL) 5 mL (range 3.6 to 6 mL) 10 mL (range \>6 to 12 mL) 17 mL (range \>12 to 24 mL) 30 mL (range \>24 mL to 44 mL) 68 mL (range \>44 to 98 mL) 118 mL (range \>98 to 175 mL)
Time frame: T = 1 hour after first dose
Population: The pharmacokinetic (PK) analysis aggregated subjects into groups by the dose given per convention according to our SAP and PK plan. Characterization of Patients who received similar doses (2mL, 5mL, 10mL, 18 mL, 30 mL, 68 mL, 118 mL, etc.) from all the cohorts were aggregated per the plan. This methodology of grouping (as described in the PK report produces meaningful API and excipient blood concentration profiles and determines conventional PK parameters for those agents.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Monotherapy: Cohort A1 | Determine Pharmacokinetic Parameter Peak Plasma (Cmax in ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 5mL | 77.81 ng/mL | Standard Deviation 38.16 |
| Monotherapy: Cohort A1 | Determine Pharmacokinetic Parameter Peak Plasma (Cmax in ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 30mL | 456.5 ng/mL | Standard Deviation 195 |
| Monotherapy: Cohort A1 | Determine Pharmacokinetic Parameter Peak Plasma (Cmax in ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 17mL | 245.8 ng/mL | Standard Deviation 119.3 |
| Monotherapy: Cohort A1 | Determine Pharmacokinetic Parameter Peak Plasma (Cmax in ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 2mL | 34.27 ng/mL | Standard Deviation 25.51 |
| Monotherapy: Cohort A1 | Determine Pharmacokinetic Parameter Peak Plasma (Cmax in ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 118mL | 1673 ng/mL | Standard Deviation 1276 |
| Monotherapy: Cohort A1 | Determine Pharmacokinetic Parameter Peak Plasma (Cmax in ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 68mL | 952.2 ng/mL | Standard Deviation 503.8 |
| Monotherapy: Cohort A1 | Determine Pharmacokinetic Parameter Peak Plasma (Cmax in ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 10mL | 153.8 ng/mL | Standard Deviation 65.75 |
| Monotherapy: Cohort B1 | Determine Pharmacokinetic Parameter Peak Plasma (Cmax in ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 17mL | 426.8 ng/mL | Standard Deviation 306.6 |
| Monotherapy: Cohort B1 | Determine Pharmacokinetic Parameter Peak Plasma (Cmax in ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 2mL | 74.93 ng/mL | Standard Deviation 70.8 |
| Monotherapy: Cohort B1 | Determine Pharmacokinetic Parameter Peak Plasma (Cmax in ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 5mL | 113.7 ng/mL | Standard Deviation 83.2 |
| Monotherapy: Cohort B1 | Determine Pharmacokinetic Parameter Peak Plasma (Cmax in ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 10mL | 300.6 ng/mL | Standard Deviation 172.6 |
| Monotherapy: Cohort B1 | Determine Pharmacokinetic Parameter Peak Plasma (Cmax in ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 30mL | 911.6 ng/mL | Standard Deviation 790.1 |
| Monotherapy: Cohort B1 | Determine Pharmacokinetic Parameter Peak Plasma (Cmax in ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 68mL | 1446 ng/mL | Standard Deviation 1245 |
| Monotherapy: Cohort B1 | Determine Pharmacokinetic Parameter Peak Plasma (Cmax in ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 118mL | 2720 ng/mL | Standard Deviation 1848 |
| Monotherapy: Cohort EA | Determine Pharmacokinetic Parameter Peak Plasma (Cmax in ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 30mL | 3.16 ng/mL | Standard Deviation 1.99 |
| Monotherapy: Cohort EA | Determine Pharmacokinetic Parameter Peak Plasma (Cmax in ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 5mL | .73 ng/mL | Standard Deviation 0.77 |
| Monotherapy: Cohort EA | Determine Pharmacokinetic Parameter Peak Plasma (Cmax in ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 118mL | 9.52 ng/mL | Standard Deviation 4.52 |
| Monotherapy: Cohort EA | Determine Pharmacokinetic Parameter Peak Plasma (Cmax in ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 68mL | 5.63 ng/mL | Standard Deviation 2.33 |
| Monotherapy: Cohort EA | Determine Pharmacokinetic Parameter Peak Plasma (Cmax in ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 17mL | 1.24 ng/mL | Standard Deviation 0.67 |
| Monotherapy: Cohort EA | Determine Pharmacokinetic Parameter Peak Plasma (Cmax in ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 10mL | .75 ng/mL | Standard Deviation 0.33 |
| Monotherapy: Cohort EA | Determine Pharmacokinetic Parameter Peak Plasma (Cmax in ng/mL) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 2mL | 1.35 ng/mL | Standard Deviation 1.7 |
Secondary
Key Pharmacokinetic Parameters, Half Live (Hours) of Each of the 3 Main Components of INT230-6.
Characterize the half life of each of the three INT230-6 components after single and multiple IT tumor site injections for safety purposes. Timepoints for sample collection were T = 0, 1, 3, 6, 24 Hours after dosing. Mean dose volume categories that were used to summarize data were as follows: 2 mL (range 0 to 3.5 mL) 5 mL (range 3.6 to 6 mL) 10 mL (range \>6 to 12 mL) 17 mL (range \>12 to 24 mL) 30 mL (range \>24 mL to 44 mL) 68 mL (range \>44 to 98 mL) 118 mL (range \>98 to 175 mL)
Time frame: T= 0, 1, 3, 6, 24 hours
Population: The pharmacokinetic (PK) analysis aggregated subjects into groups by the dose given per convention according to our SAP and PK plan. Characterization of Patients who received similar doses (2mL, 5mL, 10mL, 18 mL, 30 mL, 68 mL, 118 mL, etc.) from all the cohorts were aggregated per the plan. This methodology of grouping (as described in the PK report produces meaningful API and excipient blood concentration profiles and determines conventional PK parameters for those agents.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Monotherapy: Cohort A1 | Key Pharmacokinetic Parameters, Half Live (Hours) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 2mL | 77.98 Hours | Standard Deviation 34.92 |
| Monotherapy: Cohort A1 | Key Pharmacokinetic Parameters, Half Live (Hours) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 5mL | 130.4 Hours | Standard Deviation 129.8 |
| Monotherapy: Cohort A1 | Key Pharmacokinetic Parameters, Half Live (Hours) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 10mL | 106.3 Hours | Standard Deviation 53.58 |
| Monotherapy: Cohort A1 | Key Pharmacokinetic Parameters, Half Live (Hours) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 17mL | 78.73 Hours | Standard Deviation 66.36 |
| Monotherapy: Cohort A1 | Key Pharmacokinetic Parameters, Half Live (Hours) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 30mL | 64.77 Hours | Standard Deviation 15.18 |
| Monotherapy: Cohort A1 | Key Pharmacokinetic Parameters, Half Live (Hours) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 68mL | 129.4 Hours | Standard Deviation 125.5 |
| Monotherapy: Cohort B1 | Key Pharmacokinetic Parameters, Half Live (Hours) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 17mL | 7.33 Hours | — |
| Monotherapy: Cohort B1 | Key Pharmacokinetic Parameters, Half Live (Hours) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 30mL | 7.48 Hours | — |
| Monotherapy: Cohort B1 | Key Pharmacokinetic Parameters, Half Live (Hours) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 68mL | 3.91 Hours | Standard Deviation 2.6 |
| Monotherapy: Cohort B1 | Key Pharmacokinetic Parameters, Half Live (Hours) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 118mL | 6.18 Hours | — |
| Monotherapy: Cohort EA | Key Pharmacokinetic Parameters, Half Live (Hours) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 17mL | 20.11 Hours | Standard Deviation 7.45 |
| Monotherapy: Cohort EA | Key Pharmacokinetic Parameters, Half Live (Hours) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 68mL | 14.06 Hours | Standard Deviation 3.7 |
| Monotherapy: Cohort EA | Key Pharmacokinetic Parameters, Half Live (Hours) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 118mL | 24.48 Hours | Standard Deviation 4.76 |
| Monotherapy: Cohort EA | Key Pharmacokinetic Parameters, Half Live (Hours) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 30mL | 15.35 Hours | Standard Deviation 4.38 |
| Monotherapy: Cohort EA | Key Pharmacokinetic Parameters, Half Live (Hours) of Each of the 3 Main Components of INT230-6. | Mean INT230-6 Dose Category: 10mL | 18.82 Hours | — |
Secondary
Preliminary Efficacy: Assess the Preliminary Efficacy of INT230-6 by Measuring the Disease Control Rate (DCR) Based on the Response Evaluation Criteria in Solid Tumors (RECIST) and Immune RECIST (iRECIST) Criteria,
Assess the preliminary efficacy of INT230-6 by measuring the disease control rate (CR+PR+SD) as assessed by iRECIST. Complete response (CR) and partial response (PR) will be defined for injected tumors followed per RECIST 1.1 utilizing target lesions. Progressive disease will be determined by clinical or radiological deterioration leading to the subject being taken off-treatment at the discretion of the investigator. Stable disease (SD) is defined as any adequate assessment not considered CR, PR, or progression.
Time frame: Up to 5 years
Population: The cohorts A1/B1/EA/EC/EC2/EC3 were all INT230-6 Monotherapy Treatment and used to evaluate safety. DEC/DEC2 were INT230-6+Pembrolizumab were also used to evaluate safety. Per the Statistical Analysis Plan (SAP) the monotherapy cohorts were combined to evaluate efficacy in relation to total tumor burden (TTB) at doses of \<40%TTB or ≥40%TTB for DCR. Per the SAP the pembrolizumab cohorts were combined to evaluate DCR.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Monotherapy: Cohort A1 | Preliminary Efficacy: Assess the Preliminary Efficacy of INT230-6 by Measuring the Disease Control Rate (DCR) Based on the Response Evaluation Criteria in Solid Tumors (RECIST) and Immune RECIST (iRECIST) Criteria, | 83.3 percentage (DCR) |
| Monotherapy: Cohort B1 | Preliminary Efficacy: Assess the Preliminary Efficacy of INT230-6 by Measuring the Disease Control Rate (DCR) Based on the Response Evaluation Criteria in Solid Tumors (RECIST) and Immune RECIST (iRECIST) Criteria, | 50.0 percentage (DCR) |
| Monotherapy: Cohort EA | Preliminary Efficacy: Assess the Preliminary Efficacy of INT230-6 by Measuring the Disease Control Rate (DCR) Based on the Response Evaluation Criteria in Solid Tumors (RECIST) and Immune RECIST (iRECIST) Criteria, | 64.3 percentage (DCR) |
| Monotherapy: Cohort EC | Preliminary Efficacy: Assess the Preliminary Efficacy of INT230-6 by Measuring the Disease Control Rate (DCR) Based on the Response Evaluation Criteria in Solid Tumors (RECIST) and Immune RECIST (iRECIST) Criteria, | 83.3 percentage (DCR) |
Other Pre-specified
Exploratory: Blood, Genetic and Tissue Biomarker Identification From Cell Flow Phenotyping, Tissue Analysis, Genetic SNP Analysis.
Evaluate various tumor and anti-tumor immune response biomarkers from blood, tumor tissue that may correlate with tumor response. Flow and tissue panels may include Live-Dead, CD3, CD4, CD8, FoxP3, Ki-67, ICOS, DAPI, PD-1, LAG-3, TIM-3, CTLA-4 and analysis of blood serum cytokine such as Th1/Th2, IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12 p70, IL-13, and TNF-α.
Time frame: Up to 2 months
Other Pre-specified
Exploratory: Control or Regression of Non Injected Tumors by Measurement of Length (in Centimeters) Radio-graphically Using Computer Tomography or Magnetic Resonance Imaging.
Characterize response in non-injected lesions (up to 5) using length (cm) as the key parameter for measurement.
Time frame: Up to 18 months
Other Pre-specified
Exploratory: Overall Subject Outcome
Evaluate overall response by iRECIST including survival
Time frame: Up to 3 years