Malignant Melanoma
Conditions
Brief summary
This study aims to evaluate safety and effect of combining an oncolytic adenovirus (delolimogene mupadenorepvec; LOAd703) with atezolizumab in patients with melanoma. LOAd703 will be administered intratumorally for up to 12 injections while atezolizumab will be administered intravenously for the duration of the active study visits (up to 57 weeks). The patients are then monitored for survival for maximum study participation of 48 months. The treatments will be given every 3 weeks. The patients will then be monitored for toxicity, PK, ADA, immune responses, virus shedding, tumor response by RECIST 1.1 and survival.
Detailed description
This is a single arm, open-label, multicenter trial. This study aims to evaluate safety and effect of combining an oncolytic adenovirus (delolimogene mupadenorepvec; LOAd703) with atezolizumab in patients with melanoma. Patients will receive up to 12 LOAd703 intratumoral treatments in combination with intravenous infusions of atezolizumab. LOAd703 will be tested at two dose levels to determine the maximum tolerated dose (MTD) of LOAd703 evaluated in the study using a BOIN design. The LOAd703 dose can be divided for intratumoral injection into as many as 3 tumor lesions. Atezolizumab will be tested at a fixed dose. At least 25 response evaluable patients will be enrolled at the MTD for evaluation of their response using binominal testing. The maximum number of evaluable patients in the study is 35. The patients will then be monitored for toxicity, PK, ADA, immune responses, virus shedding, tumor response by RECIST 1.1 and survival.
Interventions
GENETICdelolimogene mupadenorepvec
LOAd703 is an oncolytic adenovirus encoding TMZ-CD40L and 4-1BBL
BIOLOGICALatezolizumab
Atezolizumab is an anti-PD-L1 antibody
Sponsors
Precision Oncology LLC
Lokon Pharma AB
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Participants treated with LOAd703 at two dose levels (1x10e11 VP and 5x10e11VP) and fixed dose of atezolizumab
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Pathological confirmation of melanoma. 2. A life expectancy of at least 3 months as per the investigator 3. Valid for Swedish patients: Patients has locally advanced melanoma or metastatic melanoma, but not eligible for complete resection of melanoma Valid for US patients: Patients has locally advanced melanoma or metastatic melanoma. 4. The patient has measurable disease (e.g., measurable tumor lesions must be present that can accurately be measured in at least one dimension with a minimum size of 10 mm by CT scan and MRI, 10 mm caliper measurement by clinical exam (when superficial), and/or 20 mm by chest X-ray). 5. Patient has at least one injectable tumor lesion that has not been irradiated or has been irradiated but disease progression documented at the site subsequent to radiation therapy. 6. The patient has received appropriate treatment with an anti-PD-1 or anti-PD-L1 antibody with or without an anti-CTLA4. 7. Valid for Swedish patients: Patients whose advanced melanoma has a B-Raf mutation must have received appropriate therapy with tyrosine kinase inhibitor(s) and/or MEK inhibitor Valid for US patients: Patients whose advanced melanoma has a B-Raf mutation may have received appropriate therapy with tyrosine kinase inhibitor(s) and/or MEK inhibitor as assessed by the investigator. 8. Age ≥ 18 years. 9. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. 10. Serum albumin ≥ 2.5 mg/dL. 11. Absolute neutrophil count (ANC) ≥1.0 x 10e9/L. 12. Platelet count ≥ 100 x 10e9/L. 13. Prothrombin (INR) ≤ 1.5 or prothrombin time (PT) ≤ 1.5 times ULN; and either partial thromboplastin time or activated partial thromboplastin time (PTT or aPTT) ≤ 1.5 times the ULN. 14. Bilirubin \< 1.5 times the institutional upper limit of normal (ULN). 15. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 (≤ 5 if liver metastases are present) times the institutional ULN. 16. The patient must have signed informed consent.
Exclusion criteria
1. Malignant melanoma that is uveal. 2. Subjects considered by the investigator to have rapid clinical progression due to melanoma 3. Subjects must not have greater than 3 cerebral melanoma metastases, and/or clinically active cerebral melanoma metastases, and/or a requirement for corticosteroid therapy, and/or carcinomatous meningitis regardless of clinical stability. 4. Any concurrent treatment that would interfere with the effect mechanisms of atezolizumab and LOAd703, including, but not limited to, continuous high-dose corticosteroids (\>10 mg per day), lymphodepleting antibodies, or cytotoxic agents. 5. Treatment with inhibitors of immune function, such as lymphotoxic monoclonal antibodies (e.g., alemtuzumab), or rapamycin/rapamycin analogs, or cytotoxic agents within 21 days of the first dose of LOAd703/atezolizumab. 6. Therapeutic treatment with systemic antibiotics within 14 days of the first dose of LOAd703/atezolizumab. 7. Treatment with biologic therapy within 21 days of the first dose of LOAd703/atezolizumab. 8. Treatment with cytotoxic anticancer therapy within 14 days of the first dose of LOAd703/atezolizumab. 9. Treatment with wide-field radiation within 14 days of the first dose of LOAd703/atezolizumab. 10. Prior treatment with an adenovirus-based gene therapy. 11. Use of any investigational agents within 21 days of the first dose of LOAd703/atezolizumab. 12. The use of systemic immunostimulatory agents (including, but not limited to, interferons and IL2) are prohibited within 21 days or 5 half-lives (whichever is longer) of the first dose of LOAd703/atezolizumab. 13. Failed resolution/improvement of AEs including those related to anti-PD-1/anti-PD-L1 to grade 0-1 and requirement for treatment with \>10 mg/day prednisone (or equivalent) for at least two weeks prior to registration. 14. History of CTCAE grade 4 immune-related AEs from monotherapy using an anti-PD-1/anti-PD-L1 antibody. 15. History of CTCAE grade 4 AE that require steroid treatment (\>10 mg/day prednisone or equivalent) for \>12 weeks. 16. Patients requiring warfarin are not eligible (low molecular weight heparin is permitted). 17. Women who are pregnant (as confirmed by pregnancy test during screening in applicable patients), breastfeeding, or planning to become pregnant during the study period, or women of childbearing potential who are not using acceptable highly effective contraceptive methods. A woman is considered of childbearing potential if she is not surgically sterile or is less than 1 year since her last menstrual period. The following are acceptable as highly effective contraceptive methods: combined (estrogen- and progesterone-containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progesterone-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion and vasectomized partner or abstinence of heterosexual intercourse during the entire study period (depending on the preferred and usual life style of the subject). 18. Men who do not consent to the use of condoms during intercourse during study participation or has a partner of childbearing potential, who will not use any of the highly effective contraceptive methods exemplified in
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tolerability Evaluated by NCI CTCAE v5.0 | Up to 57 weeks post treatment initiation | The AE reporting period begins upon receiving the first LOAd703 and/or atezolizumab treatment and continues until final visit at week 57 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | From treatment initiation until last patient last visit, assessed up till 36 months | Survival status of patients. Overall survival is defined as the time from the first dose of study treatment (LOAd703 and/or atezolizumab) until death. |
| Antibodies Against LOAd703 | Up to 57 weeks post treatment initiation | Fold change between baseline and evaluation visit for anti-adenovirus antibodies (LOAd703). The baseline is the last available measurement taken before the first LOAd703 treatment. Evaluation is a measurement taken from subjects receiving at least 3 LOAd703 treatments. |
| Overall Response Rate | Up to 57 weeks post treatment initiation | Tumor size evaluations accordingly to RECIST 1.1.Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable disease (SD), Neither PR nor progressive disease, Progressive disease (PD), \>20% increase in the sum of the longest diameter of target lesions. Overall Response (OR) = number of participants with CR or PR. |
| Virus Shedding | Up to 57 weeks post treatment initiation | Number of samples analyzed that were positive for virus particles in shedding samples. |
| Overall Survival (Number of Participants With Event) | From treatment initiation until last patient last visit, assessed up till 36 months | Survival status of patients described by number of participants with event. |
| Immune Cell Phenotype | Up to 57 weeks post treatment initiation | The ratio for CD8+/Treg cells analyzed in blood at baseline and evaluation visit as determined by flow cytometry. The baseline is the last available measurement taken before the first LOAd703 treatment. Evaluation is a measurement taken from subjects receiving at least 3 LOAd703 treatments. |
Countries
Sweden, United States
Participant flow
Pre-assignment details
Overall, a total of 26 subjects signed the informed consent, 2 out of 26 subjects were screening failures and 24 out of 26 subjects were enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| Group 1 LOAd703 1x10e11 VP Plus Atezolizumab Delolimogene mupadenorepvec (1x10e11 VP) plus atezolizumab
delolimogene mupadenorepvec: LOAd703 is an oncolytic adenovirus encoding TMZ-CD40L and 4-1BBL
atezolizumab: Atezolizumab is an anti-PD-L1 antibody | 7 |
| Group 2 LOAd703 5x10e11 VP Plus Atezolizumab Delolimogene mupadenorepvec (5x10e11 VP) plus atezolizumab
delolimogene mupadenorepvec: LOAd703 is an oncolytic adenovirus encoding TMZ-CD40L and 4-1BBL
atezolizumab: Atezolizumab is an anti-PD-L1 antibody | 17 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Group 1: LOAd703 Dose Level 1x10e11 VP | Death | 4 | 0 |
| Group 2: LOAd703 Dose Level 5x10e11 VP | Death | 0 | 7 |
| Group 2: LOAd703 Dose Level 5x10e11 VP | Lost to Follow-up | 0 | 1 |
| Group 2: LOAd703 Dose Level 5x10e11 VP | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Group 2 LOAd703 5x10e11 VP Plus Atezolizumab | Total | Group 1 LOAd703 1x10e11 VP Plus Atezolizumab |
|---|---|---|---|
| Age, Continuous | 60.0 years STANDARD_DEVIATION 13.4 | 61.5 years STANDARD_DEVIATION 12.6 | 65.3 years STANDARD_DEVIATION 10.2 |
| Disease stage at initial diagnosis Stage 0 | 1 Participants | 1 Participants | 0 Participants |
| Disease stage at initial diagnosis Stage I | 3 Participants | 5 Participants | 2 Participants |
| Disease stage at initial diagnosis Stage II | 2 Participants | 2 Participants | 0 Participants |
| Disease stage at initial diagnosis Stage III | 8 Participants | 12 Participants | 4 Participants |
| Disease stage at initial diagnosis Stage IV | 2 Participants | 3 Participants | 1 Participants |
| Disease stage at initial diagnosis Unknown | 1 Participants | 1 Participants | 0 Participants |
| Disease stage at study entry Stage III | 0 Participants | 0 Participants | 0 Participants |
| Disease stage at study entry Stage IV | 17 Participants | 24 Participants | 7 Participants |
| Disease stage at study entry Unknown | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 19 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 4 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) White | 14 Participants | 21 Participants | 7 Participants |
| Region of Enrollment Sweden | 12 participants | 17 participants | 5 participants |
| Region of Enrollment United States | 5 participants | 7 participants | 2 participants |
| Sex: Female, Male Female | 9 Participants | 11 Participants | 2 Participants |
| Sex: Female, Male Male | 8 Participants | 13 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 4 / 7 | 7 / 17 |
| other Total, other adverse events | 7 / 7 | 17 / 17 |
| serious Total, serious adverse events | 2 / 7 | 5 / 17 |
Outcome results
Primary
Tolerability Evaluated by NCI CTCAE v5.0
The AE reporting period begins upon receiving the first LOAd703 and/or atezolizumab treatment and continues until final visit at week 57
Time frame: Up to 57 weeks post treatment initiation
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1 LOAd703 1x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | AEs Not Related to LOAd703 or Atezolizumab - Grade 5 | 1 Number of Events |
| Group 1 LOAd703 1x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | AEs Related to Atezolizumab - Grade 4 | 0 Number of Events |
| Group 1 LOAd703 1x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | All Adverse Events (AEs) | 52 Number of Events |
| Group 1 LOAd703 1x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | All Serious Adverse Events (SAEs) | 6 Number of Events |
| Group 1 LOAd703 1x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | Serious Adverse Reactions (SARs) Related to LOAd703 | 0 Number of Events |
| Group 1 LOAd703 1x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | Serious Adverse Reactions (SARs) Related to Atezolizumab | 0 Number of Events |
| Group 1 LOAd703 1x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | AEs Leading to Withdrawal from the Study | 0 Number of Events |
| Group 1 LOAd703 1x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | AEs Leading to LOAd703 Discontinuation | 4 Number of Events |
| Group 1 LOAd703 1x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | AEs Leading to Atezolizumab Discontinuation | 6 Number of Events |
| Group 1 LOAd703 1x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | AEs Leading to Death | 1 Number of Events |
| Group 1 LOAd703 1x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | AEs Related to LOAd703 | 28 Number of Events |
| Group 1 LOAd703 1x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | AEs Related to Atezolizumab | 20 Number of Events |
| Group 1 LOAd703 1x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | AEs Related to LOAd703 and/or Atezolizumab | 30 Number of Events |
| Group 1 LOAd703 1x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | AEs Related to LOAd703 - Grade 1 | 17 Number of Events |
| Group 1 LOAd703 1x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | AEs Related to LOAd703 - Grade 2 | 11 Number of Events |
| Group 1 LOAd703 1x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | AEs Related to LOAd703 - Grade 3 | 0 Number of Events |
| Group 1 LOAd703 1x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | AEs Related to LOAd703 - Grade 4 | 0 Number of Events |
| Group 1 LOAd703 1x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | AEs Related to LOAd703 - Grade 5 | 0 Number of Events |
| Group 1 LOAd703 1x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | AEs Related to Atezolizumab - Grade 1 | 10 Number of Events |
| Group 1 LOAd703 1x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | AEs Related to Atezolizumab - Grade 2 | 10 Number of Events |
| Group 1 LOAd703 1x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | AEs Related to Atezolizumab - Grade 5 | 0 Number of Events |
| Group 1 LOAd703 1x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | AEs Not Related to LOAd703 or Atezolizumab - Grade 1 | 7 Number of Events |
| Group 1 LOAd703 1x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | AEs Not Related to LOAd703 or Atezolizumab - Grade 2 | 7 Number of Events |
| Group 1 LOAd703 1x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | AEs Not Related to LOAd703 or Atezolizumab - Grade 3 | 7 Number of Events |
| Group 1 LOAd703 1x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | AEs Not Related to LOAd703 or Atezolizumab - Grade 4 | 0 Number of Events |
| Group 1 LOAd703 1x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | AEs Related to Atezolizumab - Grade 3 | 0 Number of Events |
| Group 2 LOAd703 5x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | AEs Related to Atezolizumab - Grade 2 | 14 Number of Events |
| Group 2 LOAd703 5x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | AEs Related to Atezolizumab - Grade 3 | 1 Number of Events |
| Group 2 LOAd703 5x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | AEs Related to LOAd703 - Grade 1 | 40 Number of Events |
| Group 2 LOAd703 5x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | AEs Not Related to LOAd703 or Atezolizumab - Grade 5 | 0 Number of Events |
| Group 2 LOAd703 5x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | AEs Related to Atezolizumab - Grade 4 | 0 Number of Events |
| Group 2 LOAd703 5x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | All Adverse Events (AEs) | 130 Number of Events |
| Group 2 LOAd703 5x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | AEs Related to LOAd703 - Grade 2 | 22 Number of Events |
| Group 2 LOAd703 5x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | All Serious Adverse Events (SAEs) | 11 Number of Events |
| Group 2 LOAd703 5x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | AEs Not Related to LOAd703 or Atezolizumab - Grade 2 | 13 Number of Events |
| Group 2 LOAd703 5x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | Serious Adverse Reactions (SARs) Related to LOAd703 | 2 Number of Events |
| Group 2 LOAd703 5x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | AEs Related to LOAd703 - Grade 3 | 2 Number of Events |
| Group 2 LOAd703 5x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | Serious Adverse Reactions (SARs) Related to Atezolizumab | 1 Number of Events |
| Group 2 LOAd703 5x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | AEs Related to Atezolizumab - Grade 5 | 0 Number of Events |
| Group 2 LOAd703 5x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | AEs Leading to Withdrawal from the Study | 0 Number of Events |
| Group 2 LOAd703 5x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | AEs Related to LOAd703 - Grade 4 | 0 Number of Events |
| Group 2 LOAd703 5x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | AEs Leading to LOAd703 Discontinuation | 4 Number of Events |
| Group 2 LOAd703 5x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | AEs Not Related to LOAd703 or Atezolizumab - Grade 4 | 2 Number of Events |
| Group 2 LOAd703 5x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | AEs Leading to Atezolizumab Discontinuation | 4 Number of Events |
| Group 2 LOAd703 5x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | AEs Related to LOAd703 - Grade 5 | 0 Number of Events |
| Group 2 LOAd703 5x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | AEs Leading to Death | 0 Number of Events |
| Group 2 LOAd703 5x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | AEs Not Related to LOAd703 or Atezolizumab - Grade 1 | 32 Number of Events |
| Group 2 LOAd703 5x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | AEs Related to LOAd703 | 64 Number of Events |
| Group 2 LOAd703 5x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | AEs Related to Atezolizumab - Grade 1 | 26 Number of Events |
| Group 2 LOAd703 5x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | AEs Related to Atezolizumab | 41 Number of Events |
| Group 2 LOAd703 5x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | AEs Not Related to LOAd703 or Atezolizumab - Grade 3 | 11 Number of Events |
| Group 2 LOAd703 5x10e11 VP Plus Atezolizumab | Tolerability Evaluated by NCI CTCAE v5.0 | AEs Related to LOAd703 and/or Atezolizumab | 72 Number of Events |
Secondary
Antibodies Against LOAd703
Fold change between baseline and evaluation visit for anti-adenovirus antibodies (LOAd703). The baseline is the last available measurement taken before the first LOAd703 treatment. Evaluation is a measurement taken from subjects receiving at least 3 LOAd703 treatments.
Time frame: Up to 57 weeks post treatment initiation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1 LOAd703 1x10e11 VP Plus Atezolizumab | Antibodies Against LOAd703 | 9.05 fold change | Standard Deviation 1.73 |
| Group 2 LOAd703 5x10e11 VP Plus Atezolizumab | Antibodies Against LOAd703 | 15.86 fold change | Standard Deviation 9.81 |
Secondary
Immune Cell Phenotype
The ratio for CD8+/Treg cells analyzed in blood at baseline and evaluation visit as determined by flow cytometry. The baseline is the last available measurement taken before the first LOAd703 treatment. Evaluation is a measurement taken from subjects receiving at least 3 LOAd703 treatments.
Time frame: Up to 57 weeks post treatment initiation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1 LOAd703 1x10e11 VP Plus Atezolizumab | Immune Cell Phenotype | 7.63 ratio | Standard Deviation 1.42 |
| Group 2 LOAd703 5x10e11 VP Plus Atezolizumab | Immune Cell Phenotype | 14.86 ratio | Standard Deviation 10.36 |
| Group 1 LOAd703 1x10e11 VP Plus Atezolizumab - Evaluation | Immune Cell Phenotype | 8.11 ratio | Standard Deviation 1.23 |
| Group 2 LOAd703 5x10e11 VP Plus Atezolizumab - Evaluation | Immune Cell Phenotype | 25.37 ratio | Standard Deviation 20.15 |
Secondary
Overall Response Rate
Tumor size evaluations accordingly to RECIST 1.1.Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable disease (SD), Neither PR nor progressive disease, Progressive disease (PD), \>20% increase in the sum of the longest diameter of target lesions. Overall Response (OR) = number of participants with CR or PR.
Time frame: Up to 57 weeks post treatment initiation
Population: ORR was evaluated in participants receiving at least 3 doses of LOAd703 and/or atezolizumab with available tumor assessment data.~Group 1 (1x10e11 VP): from a total of 7 participants, 6 met the criteria to be included in this analysis Group 2 (5x10e11 VP): from a total of 17 participants, 15 met the criteria to be included in this analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 LOAd703 1x10e11 VP Plus Atezolizumab | Overall Response Rate | 16.7 Percentage of Participants |
| Group 2 LOAd703 5x10e11 VP Plus Atezolizumab | Overall Response Rate | 20.0 Percentage of Participants |
Secondary
Overall Survival
Survival status of patients. Overall survival is defined as the time from the first dose of study treatment (LOAd703 and/or atezolizumab) until death.
Time frame: From treatment initiation until last patient last visit, assessed up till 36 months
Population: OS was evaluated in participants receiving at least 3 doses of LOAd703 and/or atezolizumab with available tumor assessment data.~Group 1 (1x10e11 VP): from a total of 7 participants, 6 met the criteria to be included in this analysis Group 2 (5x10e11 VP): from a total of 17 participants, 15 met the criteria to be included in this analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 1 LOAd703 1x10e11 VP Plus Atezolizumab | Overall Survival | 26.05 Months |
| Group 2 LOAd703 5x10e11 VP Plus Atezolizumab | Overall Survival | NA Months |
Secondary
Overall Survival (Number of Participants With Event)
Survival status of patients described by number of participants with event.
Time frame: From treatment initiation until last patient last visit, assessed up till 36 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1 LOAd703 1x10e11 VP Plus Atezolizumab | Overall Survival (Number of Participants With Event) | Number of Subjects with Event (death) | 4 Number of Participants |
| Group 1 LOAd703 1x10e11 VP Plus Atezolizumab | Overall Survival (Number of Participants With Event) | Number of Subjects Censored (at the last date known to be alive) | 3 Number of Participants |
| Group 2 LOAd703 5x10e11 VP Plus Atezolizumab | Overall Survival (Number of Participants With Event) | Number of Subjects with Event (death) | 7 Number of Participants |
| Group 2 LOAd703 5x10e11 VP Plus Atezolizumab | Overall Survival (Number of Participants With Event) | Number of Subjects Censored (at the last date known to be alive) | 10 Number of Participants |
Secondary
Virus Shedding
Number of samples analyzed that were positive for virus particles in shedding samples.
Time frame: Up to 57 weeks post treatment initiation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 LOAd703 1x10e11 VP Plus Atezolizumab | Virus Shedding | 0 number of samples |
| Group 2 LOAd703 5x10e11 VP Plus Atezolizumab | Virus Shedding | 2 number of samples |
| Group 1 LOAd703 1x10e11 VP Plus Atezolizumab - Evaluation | Virus Shedding | 0 number of samples |
| Group 2 LOAd703 5x10e11 VP Plus Atezolizumab - Evaluation | Virus Shedding | 1 number of samples |
| Group 1 LOAd703 1x10e11 VP Plus Atezolizumab - Rectal Sample | Virus Shedding | 0 number of samples |
| Group 2 LOAd703 5x10e11 VP Plus Atezolizumab - Rectal Sample | Virus Shedding | 1 number of samples |