Melanoma
Conditions
Brief summary
A Phase 2 study to investigate the efficacy and safety of lerapolturev alone or in combination with a programmed death receptor-1 (anti-PD-1) inhibitor.
Detailed description
This multi-center, open-label, randomized, Phase 2 will investigate the efficacy and safety of lerapolturev alone (Arm 1) or in combination with an anti-PD-1 inhibitor (Arm 2). Following a 6 participant safety run-in period, up to approximately 50 participants with cutaneous melanoma who previously failed anti-PD-1/L1-based therapy will be randomized 1:1 to receive either lerapolturev or lerapolturev plus an anti-PD-1.
Interventions
BIOLOGICALLerapolturev
Lerapolturev administered via direct lesion injection
BIOLOGICALAnti-PD-1 Checkpoint Inhibitor
Anti-PD-1 Checkpoint Inhibitor administered per package insert instructions
Sponsors
Istari Oncology, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. ≥ 18 years of age 2. Prior CDC-recommended vaccination series against PV, and has received a boost immunization with trivalent IPOL® (Sanofi-Pasteur SA) at least 1 week, but less than 6 weeks, prior to Day 1 a. NOTE: Patients who are unsure of their vaccination status must provide evidence of anti-PV immunity prior to enrollment, as applicable 3. Has biopsy proven unresectable cutaneous melanoma and is willing to undergo tumor biopsy prior to the first dose of study drugs and at prespecified intervals during the study 1. Patients with ocular, acral or mucosal melanoma are not eligible 2. Patients with M1c or M1d disease are NOT eligble. 3. Submission of an archival biopsy sample is allowed in lieu of the baseline tumor biopsy, provided the tissue is ≤4 months old and the participant received no intervening systemic/intratumoral anti-cancer therapy since the biopsy was acquired. 4. Must have at least 1 lesion that is amenable to biopsy. The lesion must be safely accessible as determined by the investigator and should not be located at sites that require significant risk procedures to biopsy. Examples of sites considered to be of significant risk include but are not limited to the following: the brain, lung, mediastinum, pancreas, or endoscopic procedures extending beyond the esophagus, stomach, or bowel wall. 4. Has ≥ 2 melanoma lesions that are accurately measurable by caliper or a radiological method according to RECIST 1.1 criteria 1. One lesion must be injectable- defined as a visible or palpable cutaneous, subcutaneous, or nodal melanoma lesion ≥10 mm in longest diameter or multiple injectable melanoma lesions which in aggregate have a longest diameter of ≥10 mm and where the minimum lesion size is ≥5 mm 2. Note that visceral lesions (eg, liver, lung, retroperitoneal, subpleural lesions) are not considered injectable for the purposes of this trial. 5. Has had confirmed progression of disease (PD) while receiving at least 6 weeks (\> 1 dose) of an FDA-approved anti-PD-1/L1 therapy (as monotherapy or in combination) for the treatment of melanoma. Note the following details: 1. Initial PD as defined by RECIST v1.1 2. Confirmation of PD per iRECIST must occur by repeat assessment ≥ 4 weeks from initial evidence of PD, in the absence of rapid clinical progression. 3. Those who discontinue anti-PD-1/L1 therapy after at least 6 weeks (\> 1 dose) and have confirmed PD per iRECIST within 12 weeks of their last anti-PD-1/L1 dose are also eligible, provided the anti-PD-1/L1 was not stopped due to toxicity requiring permanent discontinuation 4. Those treated with anti-PD-1/L1 in the adjuvant setting and who have biopsy-confirmed progression either while receiving anti-PD-1/L1-based therapy or ≤ 12 weeks after their last dose of anti-PD-1/L1 therapy are allowed NOTE: Adjuvant is defined as therapy received after surgical resection of disease such that the patient has no evidence of disease when the anti-PD-1/L1 therapy is initiated. Patients with known BRAF mutation must have also failed or refused to receive BRAF-targeted therapy (alone or in combination with MEK inhibitor) to be eligible. 6. Eastern Cooperative Oncology Group (ECOG) status of 0-1 7. Serum lactate dehydrogenase (LDH) levels ≤ 3 x upper limit of normal (ULN) 8. Adequate bone marrow, liver and renal function as assessed by the following: 1. Hemoglobin ≥ 9.0 g/dl, patients may be transfused 2. Lymphocyte count ≥ 0.5 x 10\^9/L (500 µL) 3. Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L (1500 µL) 4. Platelet count ≥ 100 x 10\^9/L (100,000 µL) without transfusion 5. AST, ALT, and alkaline phosphatase (ALP) ≤ 2.5 x upper limit of normal (ULN), with the following exceptions: Patients with documented liver metastases: AST and ALT ≤ 5 x ULN; Patients with documented liver or bone metastases: ALP ≤ 5 x ULN 6. Serum bilirubin ≤ 1.5 x ULN with the following exception: Patients with known Gilbert disease: serum bilirubin level ≤ 3 x ULN 7. Measured or calculated (per institutional standards) creatinine clearance ≥ 30 ml/min (GRF can also be used in place of creatinine clearance) 8. For patients not receiving therapeutic anticoagulation: INR, PT, PTT (or aPTT) ≤ 1.5 x ULN 9. Life expectancy of \>12 weeks 10. Signed informed consent form (ICF) indicating that participant understands the purpose of, and procedures required for the study, and is willing/able to participate in the study
Exclusion criteria
1. Has biopsy-proven ocular, acral or mucosal melanoma 2. Has M1c or M1d disease 3. No more than one prior systemic anti-cancer regimen (monotherapy or combination) for management of melanoma. Additional details noted below: 1. Adjuvant anti-cancer therapy administered ≥ 6 months prior to the first injection of lerapolturev does NOT count as a line of treatment. 2. Patients with BRAF mutant melanoma may enroll if they have received ≤ 2 prior lines of systemic anti-cancer therapy only if one of those lines of therapy was a BRAF-targeted regimen (alone or in combination with MEK inhibitor). 3. A line of therapy is defined as a regimen in which at least 2 doses of systemic anti-cancer therapy (monotherapy or combination) was administered, and the regimen was discontinued because of progressive disease 4. Uncontrolled tumor-related pain. Participants requiring pain medication must be on a stable regimen at study entry. 1. Symptomatic lesions amenable to palliative radiotherapy (e.g., bone metastases or metastases causing nerve impingement) should treated prior to enrollment. Patients should be recovered from the effects of radiation. There is no required minimum recovery period 2. Asymptomatic metastatic lesions that would likely cause functional deficits or intractable pain with further growth (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for loco-regional therapy if appropriate prior to enrollment 5. Grade ≥2 pleural effusion, pericardial effusion, or ascites 6. Active or history of autoimmune disease or immune deficiency within previous 2 years, with the following exceptions: 1. History of autoimmune-related endocrinopathy (e.g. adrenal insufficiency, hypothyroidism, Type 1 diabetes mellitus, etc.) that is managed by hormone replacement therapy (e.g. hydrocortisone, thyroid hormone, insulin, etc.) 2. Eczema, psoriasis, or lichen simplex chronicus with dermatologic manifestations only (eg, patients with psoriatic arthritis are excluded), provided all of the following conditions are met: i. Rash must cover \<10% of body surface area ii. Disease is well-controlled at baseline and requires only low-potency topical corticosteroids iii. No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high potency or oral corticosteroids within 12 months of Day 1 7. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan a. History of radiation pneumonitis in the radiation field (fibrosis) is allowed. 8. History of a positive HIV RNA test (HIV 1 or 2 RNA by PCR) 9. Known active hepatitis B virus (HBV) infection (chronic or acute) a. NOTE: Participants with a negative HBsAg test and a positive total hepatitis B core antibody (HBcAb) test are allowed. 10. Known active hepatitis C virus (HCV) infection a. NOTE: History of a positive HCV antibody test, but negative HCV RNA test is allowed. 11. Active tuberculosis 12. Significant cardiovascular disease, such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident within 3 months of Day 1, unstable arrhythmia, or unstable angina 13. Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks or 5 elimination half-lives- whichever is shorter, prior to treatment, or has not recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy are eligible 1. Note: Anti-PD-1/L1 within 4 weeks prior to Day 1 is allowed 2. If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment. 14. History of other malignancy within 2 years prior to Day 1, with the exception of those with a negligible risk of metastasis or death (e.g., resected cutaneous basal cell carcinoma, or other cancers with 5-year OS of \>90%) 15. Severe infection within 4 weeks prior to Day 1, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia a. Prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are allowed. 16. Prior allogeneic stem cell or solid organ transplantation 17. Treatment with a live, attenuated vaccine within 4 weeks prior to Day 1 18. Treatment with systemic immunosuppressive medication within 4 weeks prior to Day 1, with the following exceptions: 1. Participants who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible 2. Patients receiving mineralocorticoids (e.g., fludrocortisone), or systemic prednisone equivalent corticosteroid doses of \<10mg per day are eligible for the study 19. Known hypersensitivity to pembrolizumab, nivolumab, or any of the respective excipients 20. Requires therapeutic anticoagulation and cannot discontinue anticoagulation safely during the day prior, day of, and day after each lerapolturev injection a. NOTE: Participants receiving anticoagulation with warfarin at the time of study entry are allowed if they can be transitioned to an alternative anticoagulant (eg, low molecular weight heparin or direct oral anticoagulants) prior to the first dose of lerapolturev. Anyone transitioned from warfarin to an oral anticoagulant prior to the first dose of lerapolturev should have an INR \<1.5x upper limit of normal in order to participate. Antiplatelet agents (eg, aspirin, clopidogrel, etc.) are not considered anticoagulants for the purposes of this study (ie, are allowed) 21. A pregnant or nursing female, or women of child-bearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception starting from signed ICF through 150 days after last anti-PD-1 dose 22. History of human serum albumin allergy 23. History of neurological complications due to polio virus infection 24. History of agammaglobulinemia 25. Concurrent participation in a separate interventional clinical trial during this study. 26. Any underlying medical condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (e.g., compromises the participant's well-being) or that could prevent, limit, or confound protocol-specified assessments
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes From Baseline in PD-L1 Expression | 24 months | Changes from baseline in PD-L1 expression |
| Number of Participants Experiencing a Treatment-emergent Adverse Event | 24 months | The number of participants experiencing a treatment-emergent adverse event |
| Number of Participants Experiencing an Adverse Event of Special Interest (AESI) or Anti-PD-1 Immune Related Adverse Events (irAEs) | 24 months | The number of participants experiencing an AESI or irAE |
| Overall Response | 24 months | The number of patients achieving confirmed complete (CR) or partial response (PR), per RECIST 1.1 criteria |
| Number of Participants Discontinuing Study Treatment Due to Adverse Event(s) | 24 months | Number of participants discontinuing study treatment due to adverse event(s) |
| Changes From Baseline in the Number of CD8+ Tumor Infiltrating Lymphocytes (TILs) | 24 months | Changes from baseline in the number of CD8+ tumor infiltrating lymphocytes (TILs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 24 months | Overall survival (OS): time from treatment group assignment until death from any cause. |
| Duration of Response | 24 months | Duration of Response (DOR): time from confirmed objective response (CR or PR per RECIST 1.1) until unequivocal disease progression or death, whichever occurs first |
| Disease Control Rate | 24 months | The percentage of patients achieving confirmed CR, confirmed PR, or stable disease (SD) per RECIST1.1, as best response. |
| DCR-6 Months | 24 months | The number of patients achieving confirmed CR (any duration), confirmed PR (any duration) or SD (≥ 6 months) per RECIST 1.1 as best response. |
| Durable Response Rate | 24 months | The percentage of participants with confirmed CR or PR (per RECIST 1.1) lasting at least 6 months |
| Progression-free Survival (PFS) | 24 months | Progression-free survival (PFS): time (number of months) from treatment group assignment until date of documented radiologic disease progression per RECIST 1.1 or death due to any cause, whichever comes first |
Other
| Measure | Time frame | Description |
|---|---|---|
| Lerapolturev Mechanism of Action and Predictors of Response to Lerapolturev With or Without Anti-PD-1 in Patients Who Have Failed Anti-PD1/L1 -Based Therapy | 24 months | * Assessment and identification of genetic, cytologic, histologic and/or other markers in tumor biopsies and PBMC samples that may correlate with response. * Assessment of changes over time in immune markers, including, but not limited to immune cell density, T cell receptor repertoire, and chemokine and/or cytokine profile in blood, samples, and/or tissue |
| PFS Based on Subgroup | 24 months | PFS in the following subgroups: * According to treatment arm and AJCC stage at baseline * Primary versus acquired resistance as defined by Kluger et al * BRAF wild type and mutant * LDH levels at baseline * Time since last dose of anti-PD1/L1 therapy prior to randomization (≤ or \>6 weeks) * Crossover to combination arm from lerapolturev monotherapy |
| ORR Based on iRECIST | 24 months | ORR based on iRECIST criteria |
| DOR Based on iRECIST | 24 months | DOR based on iRECIST criteria |
| DRR Based on iRECIST | 24 months | DRR based on iRECIST criteria |
| DCR Based on iRECIST | 24 months | DCR based on iRECIST criteria |
| DCR-6mo Based on iRECIST | 24 months | DCR-6mo based on iRECIST criteria |
| ORR Based on Subgroup | 24 months | ORR in the following subgroups: * Acquired versus primary PD-1/L1 resistance as defined by Kluger, et al (2020) * BRAF wild type and mutant * LDH levels at baseline * Time since last dose of anti-PD1/L1 therapy prior to randomization (≤ or \>6 weeks) * Crossover to combination arm from lerapolturev monotherapy |
| DOR Based on Subgroup | 24 months | DOR in the following subgroups: * Acquired versus primary PD-1/L1 resistance as defined by Kluger, et al (2020) * BRAF wild type and mutant * LDH levels at baseline * Time since last dose of anti-PD1/L1 therapy prior to randomization (≤ or \>6 weeks) * Crossover to combination arm from lerapolturev monotherapy |
| DRR Based on Subgroup | 24 months | DRR in the following subgroups: * Acquired versus primary PD-1/L1 resistance as defined by Kluger, et al (2020) * BRAF wild type and mutant * LDH levels at baseline * Time since last dose of anti-PD1/L1 therapy prior to randomization (≤ or \>6 weeks) * Crossover to combination arm from lerapolturev monotherapy |
| DCR Based on Subgroup | 24 months | DCR in the following subgroups: * Acquired versus primary PD-1/L1 resistance as defined by Kluger, et al (2020) * BRAF wild type and mutant * LDH levels at baseline * Time since last dose of anti-PD1/L1 therapy prior to randomization (≤ or \>6 weeks) * Crossover to combination arm from lerapolturev monotherapy |
| DCR-6mo Based on Subgroup | 24 months | DCR-6mo in the following subgroups: * Acquired versus primary PD-1/L1 resistance as defined by Kluger, et al (2020) * BRAF wild type and mutant * LDH levels at baseline * Time since last dose of anti-PD1/L1 therapy prior to randomization (≤ or \>6 weeks) * Crossover to combination arm from lerapolturev monotherapy |
| OS Based on Subgroup | 24 months | OS in the following subgroups: * According to treatment arm and AJCC stage at baseline * Primary versus acquired resistance as defined by Kluger et al * BRAF wild type and mutant * LDH levels at baseline * Time since last dose of anti-PD1/L1 therapy prior to randomization (≤ or \>6 weeks) * Crossover to combination arm from lerapolturev monotherapy |
Countries
United States
Participant flow
Recruitment details
Safety-run in: lerapolturev, up to 6x10\^8 TCID50, administered on days 1, 10 and every 3 weeks thereafter. Total dose dependent on number and size of injectable lesions. Data are included in the Arm 1: lerapolturev Q3W group.
Participants by arm
| Arm | Count |
|---|---|
| Arm 1: Lerapolturev QW lerapolturev weekly for 7 weeks and every 3 weeks thereafter | 3 |
| Arm 1: Lerapolturev Q3W lerapolturev at day 1, day 10 and every 3 weeks thereafter includes data from safety run-in | 12 |
| Arm 2: Lerapolturev + Anti-PD-1 QW lerapolturev weekly for 7 weeks and every 3 or 4 weeks thereafter anti-PD-1 every 3 or 4 weeks per prescribing information starting at day 1 | 6 |
| Arm 2: Lerapolturev + Anti-PD-1 Q3/4W lerapolturev at day 1, day 10 and every 3 or 4 weeks thereafter anti-PD-1 every 3 or 4 weeks per prescribing information starting at day 10 | 6 |
| Total | 27 |
Baseline characteristics
| Characteristic | Arm 1: Lerapolturev Q3W | Arm 2: Lerapolturev + Anti-PD-1 QW | Arm 2: Lerapolturev + Anti-PD-1 Q3/4W | Arm 1: Lerapolturev QW | Total |
|---|---|---|---|---|---|
| Age, Continuous | 59 years | 67 years | 65 years | 60 years | 62 years |
| ECOG Performance Status ECOG PS 0 | 7 patients | 2 patients | 3 patients | 3 patients | 15 patients |
| ECOG Performance Status ECOG PS 1 | 5 patients | 4 patients | 3 patients | 0 patients | 12 patients |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 5 Participants | 6 Participants | 3 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 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 |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 5 Participants | 6 Participants | 3 Participants | 26 Participants |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 4 Participants | 1 Participants | 12 Participants |
| Sex: Female, Male Male | 8 Participants | 3 Participants | 2 Participants | 2 Participants | 15 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 12 | 0 / 6 | 0 / 6 | 0 / 11 |
| other Total, other adverse events | 3 / 3 | 10 / 12 | 6 / 6 | 5 / 6 | 10 / 11 |
| serious Total, serious adverse events | 1 / 3 | 0 / 12 | 2 / 6 | 2 / 6 | 3 / 11 |
Outcome results
Primary
Changes From Baseline in PD-L1 Expression
Changes from baseline in PD-L1 expression
Time frame: 24 months
Population: Company ceased operations; samples were not analyzed. Measurement values for this outcome measure are not and will not be available.
Primary
Changes From Baseline in the Number of CD8+ Tumor Infiltrating Lymphocytes (TILs)
Changes from baseline in the number of CD8+ tumor infiltrating lymphocytes (TILs)
Time frame: 24 months
Population: Company ceased operations; samples were not analyzed. Measurement values for this outcome measure are not and will not be available.
Primary
Number of Participants Discontinuing Study Treatment Due to Adverse Event(s)
Number of participants discontinuing study treatment due to adverse event(s)
Time frame: 24 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1: Lerapolturev QW | Number of Participants Discontinuing Study Treatment Due to Adverse Event(s) | 0 Participants |
| Arm 1: Lerapolturev Q3W | Number of Participants Discontinuing Study Treatment Due to Adverse Event(s) | 0 Participants |
| Arm 2: Lerapolturev + Anti-PD-1 QW | Number of Participants Discontinuing Study Treatment Due to Adverse Event(s) | 2 Participants |
| Arm 2: Lerapolturev + Anti-PD-1 Q3/4W | Number of Participants Discontinuing Study Treatment Due to Adverse Event(s) | 1 Participants |
Primary
Number of Participants Experiencing an Adverse Event of Special Interest (AESI) or Anti-PD-1 Immune Related Adverse Events (irAEs)
The number of participants experiencing an AESI or irAE
Time frame: 24 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm 1: Lerapolturev QW | Number of Participants Experiencing an Adverse Event of Special Interest (AESI) or Anti-PD-1 Immune Related Adverse Events (irAEs) | Adverse Events of Special Interest | 0 Participants |
| Arm 1: Lerapolturev QW | Number of Participants Experiencing an Adverse Event of Special Interest (AESI) or Anti-PD-1 Immune Related Adverse Events (irAEs) | No AESI or IrAE reported | 3 Participants |
| Arm 1: Lerapolturev QW | Number of Participants Experiencing an Adverse Event of Special Interest (AESI) or Anti-PD-1 Immune Related Adverse Events (irAEs) | Immune Related Adverse Events | 0 Participants |
| Arm 1: Lerapolturev Q3W | Number of Participants Experiencing an Adverse Event of Special Interest (AESI) or Anti-PD-1 Immune Related Adverse Events (irAEs) | Adverse Events of Special Interest | 0 Participants |
| Arm 1: Lerapolturev Q3W | Number of Participants Experiencing an Adverse Event of Special Interest (AESI) or Anti-PD-1 Immune Related Adverse Events (irAEs) | No AESI or IrAE reported | 12 Participants |
| Arm 1: Lerapolturev Q3W | Number of Participants Experiencing an Adverse Event of Special Interest (AESI) or Anti-PD-1 Immune Related Adverse Events (irAEs) | Immune Related Adverse Events | 0 Participants |
| Arm 2: Lerapolturev + Anti-PD-1 QW | Number of Participants Experiencing an Adverse Event of Special Interest (AESI) or Anti-PD-1 Immune Related Adverse Events (irAEs) | Immune Related Adverse Events | 2 Participants |
| Arm 2: Lerapolturev + Anti-PD-1 QW | Number of Participants Experiencing an Adverse Event of Special Interest (AESI) or Anti-PD-1 Immune Related Adverse Events (irAEs) | Adverse Events of Special Interest | 1 Participants |
| Arm 2: Lerapolturev + Anti-PD-1 QW | Number of Participants Experiencing an Adverse Event of Special Interest (AESI) or Anti-PD-1 Immune Related Adverse Events (irAEs) | No AESI or IrAE reported | 3 Participants |
| Arm 2: Lerapolturev + Anti-PD-1 Q3/4W | Number of Participants Experiencing an Adverse Event of Special Interest (AESI) or Anti-PD-1 Immune Related Adverse Events (irAEs) | Adverse Events of Special Interest | 0 Participants |
| Arm 2: Lerapolturev + Anti-PD-1 Q3/4W | Number of Participants Experiencing an Adverse Event of Special Interest (AESI) or Anti-PD-1 Immune Related Adverse Events (irAEs) | No AESI or IrAE reported | 6 Participants |
| Arm 2: Lerapolturev + Anti-PD-1 Q3/4W | Number of Participants Experiencing an Adverse Event of Special Interest (AESI) or Anti-PD-1 Immune Related Adverse Events (irAEs) | Immune Related Adverse Events | 0 Participants |
Primary
Number of Participants Experiencing a Treatment-emergent Adverse Event
The number of participants experiencing a treatment-emergent adverse event
Time frame: 24 months
Population: The number of participants experiencing a treatment-emergent adverse event are reported here. Detailed data on frequency and severity is reported under Adverse Events.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1: Lerapolturev QW | Number of Participants Experiencing a Treatment-emergent Adverse Event | 3 Participants |
| Arm 1: Lerapolturev Q3W | Number of Participants Experiencing a Treatment-emergent Adverse Event | 10 Participants |
| Arm 2: Lerapolturev + Anti-PD-1 QW | Number of Participants Experiencing a Treatment-emergent Adverse Event | 6 Participants |
| Arm 2: Lerapolturev + Anti-PD-1 Q3/4W | Number of Participants Experiencing a Treatment-emergent Adverse Event | 5 Participants |
Primary
Overall Response
The number of patients achieving confirmed complete (CR) or partial response (PR), per RECIST 1.1 criteria
Time frame: 24 months
Population: Participants received at least one lerapolturev injection and had at least 1 post-baseline assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1: Lerapolturev QW | Overall Response | 0 Participants |
| Arm 1: Lerapolturev Q3W | Overall Response | 1 Participants |
| Arm 2: Lerapolturev + Anti-PD-1 QW | Overall Response | 1 Participants |
| Arm 2: Lerapolturev + Anti-PD-1 Q3/4W | Overall Response | 0 Participants |
Secondary
DCR-6 Months
The number of patients achieving confirmed CR (any duration), confirmed PR (any duration) or SD (≥ 6 months) per RECIST 1.1 as best response.
Time frame: 24 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1: Lerapolturev QW | DCR-6 Months | 0 Participants |
| Arm 1: Lerapolturev Q3W | DCR-6 Months | 1 Participants |
| Arm 2: Lerapolturev + Anti-PD-1 QW | DCR-6 Months | 1 Participants |
| Arm 2: Lerapolturev + Anti-PD-1 Q3/4W | DCR-6 Months | 0 Participants |
Secondary
Disease Control Rate
The percentage of patients achieving confirmed CR, confirmed PR, or stable disease (SD) per RECIST1.1, as best response.
Time frame: 24 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: Lerapolturev QW | Disease Control Rate | 67 percentage of patients |
| Arm 1: Lerapolturev Q3W | Disease Control Rate | 42 percentage of patients |
| Arm 2: Lerapolturev + Anti-PD-1 QW | Disease Control Rate | 60 percentage of patients |
| Arm 2: Lerapolturev + Anti-PD-1 Q3/4W | Disease Control Rate | 20 percentage of patients |
Secondary
Durable Response Rate
The percentage of participants with confirmed CR or PR (per RECIST 1.1) lasting at least 6 months
Time frame: 24 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: Lerapolturev QW | Durable Response Rate | 0 percentage of patients |
| Arm 1: Lerapolturev Q3W | Durable Response Rate | 0 percentage of patients |
| Arm 2: Lerapolturev + Anti-PD-1 QW | Durable Response Rate | 0 percentage of patients |
| Arm 2: Lerapolturev + Anti-PD-1 Q3/4W | Durable Response Rate | 0 percentage of patients |
Secondary
Duration of Response
Duration of Response (DOR): time from confirmed objective response (CR or PR per RECIST 1.1) until unequivocal disease progression or death, whichever occurs first
Time frame: 24 months
Population: Participants had at least one dose of lerapolturev and at least one post-baseline assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 1: Lerapolturev QW | Duration of Response | NA months |
| Arm 1: Lerapolturev Q3W | Duration of Response | NA months |
| Arm 2: Lerapolturev + Anti-PD-1 QW | Duration of Response | NA months |
| Arm 2: Lerapolturev + Anti-PD-1 Q3/4W | Duration of Response | NA months |
Secondary
Overall Survival
Overall survival (OS): time from treatment group assignment until death from any cause.
Time frame: 24 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 1: Lerapolturev QW | Overall Survival | 8.5 months |
| Arm 1: Lerapolturev Q3W | Overall Survival | 4.3 months |
| Arm 2: Lerapolturev + Anti-PD-1 QW | Overall Survival | NA months |
| Arm 2: Lerapolturev + Anti-PD-1 Q3/4W | Overall Survival | 10.5 months |
Secondary
Progression-free Survival (PFS)
Progression-free survival (PFS): time (number of months) from treatment group assignment until date of documented radiologic disease progression per RECIST 1.1 or death due to any cause, whichever comes first
Time frame: 24 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 1: Lerapolturev QW | Progression-free Survival (PFS) | 2.2 months |
| Arm 1: Lerapolturev Q3W | Progression-free Survival (PFS) | 1.9 months |
| Arm 2: Lerapolturev + Anti-PD-1 QW | Progression-free Survival (PFS) | 3.7 months |
| Arm 2: Lerapolturev + Anti-PD-1 Q3/4W | Progression-free Survival (PFS) | 1.6 months |
Other Pre-specified
DCR-6mo Based on iRECIST
DCR-6mo based on iRECIST criteria
Time frame: 24 months
Population: Outcome measure not evaluated
Other Pre-specified
DCR-6mo Based on Subgroup
DCR-6mo in the following subgroups: * Acquired versus primary PD-1/L1 resistance as defined by Kluger, et al (2020) * BRAF wild type and mutant * LDH levels at baseline * Time since last dose of anti-PD1/L1 therapy prior to randomization (≤ or \>6 weeks) * Crossover to combination arm from lerapolturev monotherapy
Time frame: 24 months
Population: Outcome measure not evaluated
Other Pre-specified
DCR Based on iRECIST
DCR based on iRECIST criteria
Time frame: 24 months
Population: Outcome measure not evaluated
Other Pre-specified
DCR Based on Subgroup
DCR in the following subgroups: * Acquired versus primary PD-1/L1 resistance as defined by Kluger, et al (2020) * BRAF wild type and mutant * LDH levels at baseline * Time since last dose of anti-PD1/L1 therapy prior to randomization (≤ or \>6 weeks) * Crossover to combination arm from lerapolturev monotherapy
Time frame: 24 months
Population: Outcome measure not evaluated
Other Pre-specified
DOR Based on iRECIST
DOR based on iRECIST criteria
Time frame: 24 months
Population: Outcome measure not evaluated
Other Pre-specified
DOR Based on Subgroup
DOR in the following subgroups: * Acquired versus primary PD-1/L1 resistance as defined by Kluger, et al (2020) * BRAF wild type and mutant * LDH levels at baseline * Time since last dose of anti-PD1/L1 therapy prior to randomization (≤ or \>6 weeks) * Crossover to combination arm from lerapolturev monotherapy
Time frame: 24 months
Population: Outcome measure not evaluated
Other Pre-specified
DRR Based on iRECIST
DRR based on iRECIST criteria
Time frame: 24 months
Population: Outcome measure not evaluated
Other Pre-specified
DRR Based on Subgroup
DRR in the following subgroups: * Acquired versus primary PD-1/L1 resistance as defined by Kluger, et al (2020) * BRAF wild type and mutant * LDH levels at baseline * Time since last dose of anti-PD1/L1 therapy prior to randomization (≤ or \>6 weeks) * Crossover to combination arm from lerapolturev monotherapy
Time frame: 24 months
Population: Outcome measure not evaluated
Other Pre-specified
Lerapolturev Mechanism of Action and Predictors of Response to Lerapolturev With or Without Anti-PD-1 in Patients Who Have Failed Anti-PD1/L1 -Based Therapy
* Assessment and identification of genetic, cytologic, histologic and/or other markers in tumor biopsies and PBMC samples that may correlate with response. * Assessment of changes over time in immune markers, including, but not limited to immune cell density, T cell receptor repertoire, and chemokine and/or cytokine profile in blood, samples, and/or tissue
Time frame: 24 months
Population: Outcome measure not evaluated
Other Pre-specified
ORR Based on iRECIST
ORR based on iRECIST criteria
Time frame: 24 months
Population: Outcome measure not evaluated
Other Pre-specified
ORR Based on Subgroup
ORR in the following subgroups: * Acquired versus primary PD-1/L1 resistance as defined by Kluger, et al (2020) * BRAF wild type and mutant * LDH levels at baseline * Time since last dose of anti-PD1/L1 therapy prior to randomization (≤ or \>6 weeks) * Crossover to combination arm from lerapolturev monotherapy
Time frame: 24 months
Population: Outcome measure not evaluated
Other Pre-specified
OS Based on Subgroup
OS in the following subgroups: * According to treatment arm and AJCC stage at baseline * Primary versus acquired resistance as defined by Kluger et al * BRAF wild type and mutant * LDH levels at baseline * Time since last dose of anti-PD1/L1 therapy prior to randomization (≤ or \>6 weeks) * Crossover to combination arm from lerapolturev monotherapy
Time frame: 24 months
Population: Outcome measure not evaluated
Other Pre-specified
PFS Based on Subgroup
PFS in the following subgroups: * According to treatment arm and AJCC stage at baseline * Primary versus acquired resistance as defined by Kluger et al * BRAF wild type and mutant * LDH levels at baseline * Time since last dose of anti-PD1/L1 therapy prior to randomization (≤ or \>6 weeks) * Crossover to combination arm from lerapolturev monotherapy
Time frame: 24 months
Population: Outcome measure not evaluated