Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Pelareorep, Reovirus serotype 3 Dearing Strain, Wild-type Reovirus
REOLYSIN · 16 trials · 25 indications
Proportion of patients with complete response \[CR\], partial response \[PR\] assessed by the investigators and/or central reader according to RECIST v1.1
Overall response rate at week 16 according to RECIST V1.1
A DLT is defined as one of the following toxicities: * Grade 4 neutropenia (absolute neutrophil count \[ANC\] \< 500/µL) lasting 5 days or more. * Grade 3 to 4 thrombocytopenia associated with bleeding requiring platelet transfusion * Cardiac dysfunction: Grade \> 3 left ventricular systolic dysfunction or grade \> 2 myocarditis * Any grade 3-4 treatment-emergent non-hematologic adverse event (AE) clearly unrelated to the underlying disease and considered to be at least possibly related to protocol therapy
The Escalation with Overdose Control (EWOC) design will be used to identify the MTD.
A DLT is defined as one of the following toxicities: * Grade 4 neutropenia (absolute neutrophil count \[ANC\] \< 500/µL) lasting 5 days or more. * Grade 3 to 4 thrombocytopenia associated with bleeding requiring platelet transfusion * Cardiac dysfunction: Grade \> 3 left ventricular systolic dysfunction or grade \> 2 myocarditis * Any grade 3-4 treatment-emergent non-hematologic adverse event (AE) clearly unrelated to the underlying disease and considered to be at least possibly related to protocol therapy
The safety of the bortezomib, dexamethasone, and wild-type reovirus combination will be assessed by the evaluation of the type, frequency, and severity of adverse events.
Proportion of patients with complete response \[CR\], partial response \[PR\] assessed by the investigators and/or central reader according to RECIST v1.1
DCR (complete response \[CR\], partial response \[PR\], and stable disease \[SD\]) assessed by the investigators according to RECIST v 1.1.
OS is defined as the time from date of first treatment to death from any cause
| Arm | Type | Description |
|---|---|---|
| REOLYSIN, paclitaxel, carboplatin | ACTIVE_COMPARATOR | - |
| placebo, paclitaxel, carboplatin | PLACEBO_COMPARATOR | - |
| Paclitaxel plus Reolysin | EXPERIMENTAL | Paclitaxel given weekly on days 1, 8, 15 every 4 weeks plus reolysin days 1, 2, 8, 9, 15 and 16. |
| Paclitaxel | ACTIVE_COMPARATOR | Paclitaxel given weekly on days 1, 8 and 15 every 4 weeks. |
| Arm A | EXPERIMENTAL | - |
| Arm B | EXPERIMENTAL | - |
| Cohort 1 | ACTIVE_COMPARATOR | Patients receive paclitaxel alone. |
| Cohort 2 | EXPERIMENTAL | Patients receive pelareorep + paclitaxel. |
| Cohort 3 | EXPERIMENTAL | Patients receive pelareorep + paclitaxel + avelumab. |
| Arm 1 | EXPERIMENTAL | Patients receive dexamethasone IV on days 1, 2, 8, 9, 15, and 16, carfilzomib IV over 30 minutes on days 1, 2, 8, 9, 15, and 16, and nivolumab IV over 30 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
| Arm 2 | EXPERIMENTAL | Patients receive dexamethasone IV on days 1, 2, 8, 9, 15, and 16, pelareorep IV on days 1, 2, 8, 9, 15, and 16, carfilzomib IV over 30 minutes on days 1, 2, 8, 9, 15, and 16, and nivolumab IV over 30 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
| Arm 3 (expansion) | EXPERIMENTAL | Patients receive dexamethasone IV on days 1, 2, 8, 9, 15, and 16, pelareorep IV on days 1, 2, 8, 9, 15, and 16, carfilzomib IV over 30 minutes on days 1, 2, 8, 9, 15, and 16, and nivolumab IV over 30 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
| Treatment (dexamethasone, bortezomib, wild-type reovirus) | EXPERIMENTAL | Patients receive dexamethasone PO, IV, or IM and bortezomib SC (preferably) or IV over 3-5 seconds on days 1, 8, and 15. Patients also receive wild-type reovirus IV over 60 minutes on days 1, 2, 8, 9, 15, and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
| Cohort 1: Metastatic Pancreatic Cancer 1L | EXPERIMENTAL | Patients with first-line (1L) locally advanced/metastatic unresectable pancreatic ductal adenocarcinoma (PDAC): Pelareorep and atezolizumab added to gemcitabine and nab-paclitaxel |
| Cohort 2: Metastatic Colorectal Cancer 1L (MSI-H/dMMR) | EXPERIMENTAL | Patients with 1L metastatic colorectal cancer (mCRC), limited to microsatellite instability-high (MSIH) or mismatch repair deficient (dMMR) tumors: Pelareorep and atezolizumab |
| Cohort 3: Metastatic Colorectal Cancer 3L | EXPERIMENTAL | Patients with third-line (3L) mCRC independent of microsatellite instability (MSI)/dMMR status: Pelareorep and atezolizumab added to trifluridine/tipiracil |
| Cohort 4: Metastatic Unresectable Anal Cancer >/=2L | EXPERIMENTAL | Patients with \>/= 2L locally advanced/metastatic unresectable squamous cell carcinoma of the anal canal (SCCA) of viral or non-viral origin after prior systemic chemotherapy: Pelareorep and atezolizumab |
| Cohort 5: Metastatic PDAC 1L | EXPERIMENTAL | Patients with 1L metastatic PDAC: Pelareorep and modified FOLFIRINOX (mFOLFIRINOX) with or without atezolizumab |
| Name | Type | Description |
|---|---|---|
| REOLYSIN | BIOLOGICAL | 3E10 TCID50, 1 hour intravenous infusion, administered on Days 1, 2, 3, 4 and 5 of a 21 day cycle |
| Carboplatin | DRUG | 5 AUC mg/mL min, 30 min intravenous infusion, given on Day 1 of a 21 day cycle |
| Paclitaxel | DRUG | 175 mg/m2, 3 hour intravenous infusion, given on Day 1 of a 21 day cycle |
| Placebo | DRUG | Placebo |
| Bevacizumab | DRUG | Bevacizumab (5 mg/kg) IV infusion |
| FOLFIRI | DRUG | irinotecan (180mg/m2), leucovorin 400 mg/m2 ± 5-FU (400 mg/m2) IV infusion |
| Pelareorep | DRUG | pelareorep 4.5 x 10\^10 TCID50 IV infusion |
| Avelumab | DRUG | Avelumab 10 mg/kg (not more than 800 mg) 1-hour IV infusion days 3 and 17 of a 28-day cycle. |
| Gemcitabine | DRUG | 800 mg/m2 30-min infusion on Days 1 and 8 of a 21-day cycle. |
| REOLYSIN® | BIOLOGICAL | 3x10E10 TCID50, 1 hour intravenous infusion, administered on Days 1, 2, 3, 4 and 5 of a 21 day cycle |
| Carfilzomib | DRUG | Given IV |
| Dexamethasone | DRUG | Given IV |
| Nivolumab | BIOLOGICAL | Given IV |
| Bortezomib | DRUG | Given SC or IV |
| Laboratory Biomarker Analysis | OTHER | Correlative studies |
| Pharmacological Study | OTHER | Correlative studies |
| Wild-type Reovirus | BIOLOGICAL | Given IV |
| Atezolizumab | DRUG | Atezolizumab 840 mg IV infusion |
| Gemcitabine and nab-paclitaxel | DRUG | Gemcitabine (1,000 mg/m2) and nab-paclitaxel (125 mg/m2) |
| Trifluridine Tipiracil | DRUG | Trifluridine/tipiracil administered at a 35 mg/m2 dose orally twice daily |
| mFOLFIRINOX Treatment Regimen | DRUG | mFOLFIRINOX- IV oxaliplatin 85 mg/m2; IV leucovorin 400 mg/m2; IV irinotecan 150 mg/m2; 5-FU 2400 mg/m2 by 46-hour infusion, per local standard of care |
| Chemotherapy | DRUG | Patients may be treated with one of three chemotherapy backbone regimens. The decision on the chemotherapy backbone is based on physician preference.This includes either: a) Gemcitabine or b) Irinotecan or c)Leucovorin followed by 5-fluorouracil |
| Irinotecan | DRUG | 125 mg/m2 intravenous infusion over 90 minutes on Day 1 of a 21-day cyle or |
| Leucovorin | DRUG | Leucovorin (LV) followed by 5-fluorouracil (5FU). LV 200 mg/m2 intravenous infusion over 2 hours on Day 1, 5FU 200 mg/m2 intravenous infusion bolus over 5-10 minutes on Day 1, followed by 5FU 1200 mg/m2 continuous intravenous infusion over 22 hours on Day 1 of a 21-day cycle |
| 5-fluorouracil | DRUG | Leucovorin (LV) followed by 5-fluorouracil (5FU). LV 200 mg/m2 intravenous infusion over 2 hours on Day 1, 5FU 200 mg/m2 intravenous infusion bolus over 5-10 minutes on Day 1, followed by 5FU 1200 mg/m2 continuous intravenous infusion over 22 hours on Day 1 of a 21-day cycle |
| Pembrolizumab | DRUG | Pembrolizumab, 2 mg/kg intravenous infusion 30 minutes on Day 8 of a 21-day cycle |
| Fluorouracil (5-FU) | DRUG | 400 mg/m2 intravenous bolus followed by 2400 mg/m2 as a continuous intravenous infusion over 46 hours administered on Day 1 every 2 weeks. |
Inclusion Criteria: Each patient MUST: * have recurrent or metastatic (R/M) histologically confirmed squamous cell carcinoma (SCC) of the head and neck (oropharynx, oral cavity, larynx, hypopharynx) or squamous cell nasopharynx cancer (NPC) with distal metastasis(es) and no secondary cancers (Patie...
REOLYSIN is an investigational oncology therapy developed by Oncolytics Biotech Inc. (ticker ONCY). It has been studied in several cancer types, including non-small cell lung carcinoma, squamous cell carcinoma of the head and neck, KRAS mutant metastatic colorectal cancer, malignant glioma, metastatic breast cancer, and metastatic melanoma. It remains in clinical development and is not approved for commercial use.
REOLYSIN has been studied in patients with advanced solid tumors, including metastatic breast cancer, KRAS mutant metastatic colorectal cancer, platinum-refractory squamous cell carcinoma of the head and neck, pancreatic adenocarcinoma, non-small cell lung carcinoma, malignant glioma, and metastatic melanoma. It is an investigational agent and has not been approved for any indication.
REOLYSIN is developed by Oncolytics Biotech Inc., which trades under the ticker ONCY. The company has sponsored the clinical trial program evaluating REOLYSIN across multiple cancer indications, including breast cancer, colorectal cancer, head and neck cancer, and pancreatic adenocarcinoma.
REOLYSIN has been evaluated in Phase 1, Phase 2, and Phase 3 clinical trials. The program includes a completed Phase 3 study in platinum-refractory head and neck cancers and completed Phase 2 studies in metastatic breast cancer. REOLYSIN is investigational and has not received FDA approval.
REOLYSIN has been studied in completed trials including NCT01166542, a Phase 3 study in platinum-refractory head and neck cancers with 167 patients, and NCT01656538, a Phase 2 study in advanced or metastatic breast cancer with 81 patients. Other completed trials include NCT02620423 in pancreatic adenocarcinoma and NCT01274624 in KRAS mutant metastatic colorectal cancer.
Yes, REOLYSIN and REOLYSIN® refer to the same investigational oncology drug developed by Oncolytics Biotech Inc. The registered trademark symbol is simply a formal notation of the product name. Both names appear in the clinical trial titles for the same development program.