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Regorafenib · 3 trials · 4 indications
To determine the effect of RegoNivo on overall survival (OS) (death from any cause) in the overall study population and in the Asian sub-population. Overall survival is defined as the interval from the date of randomisation to date of death from any cause, or the date last known alive.
will be defined according to RECIST 1.1.
Tumor response was evaluated as ORR per RECIST 1.1 by local assessments for all tumor types, except for GBM/AA, where ORR per RANO by local assessment was used. ORR was defined as the proportion of participants with best overall response of complete response (CR) or partial response (PR). Participants for whom best overall tumor response was not CR or PR, as well as participants without any post-baseline tumor assessment were considered non-responders. Descriptive statistics were done, no inferential statistical analyses were performed.
| Arm | Type | Description |
|---|---|---|
| RegoNivo | EXPERIMENTAL | Participants in the RegoNivo arm will; 1. self-administer 90mg (3x30mg) of regorafenib days 1-21 of each 28-day treatment cycle and; 2. receive intravenous nivolumab 240 mg day 1 of each 14 day cycle until disease progression or prohibitive adverse events as per protocol, given in hospital by infusion. After 2 months, patients whose disease is controlled may have nivolumab administered 480 mg every 28 days. |
| Standard of Care | ACTIVE_COMPARATOR | Participants in the control arm will receive investigator choice chemotherapy with any of the following agents * taxane (paclitaxel or docetaxel) * irinotecan or * oral trifluridine/tipiracil (TAS102) All treatment groups will receive Best Supportive Care (BSC). |
| Nivolumab Combined With FOLFOX and Regorafenib | EXPERIMENTAL | Each treatment cycle consists of 28 days. Patients will initially receive induction therapy with regorafenib (80 mg on days 1-21 of the 28-day cycle) and nivolumab (240 mg on days 1 and 15 of the 28-day cycle). Starting on cycle 2, day 1, patients will also receive FOLFOX chemotherapy with oxaliplatin (85 mg/m2 IV), leucovorin (400 mg/m2 IV), 5-FU (400 mg/m2 IV bolus), and 5-FU (2400 mg/m2/day continuous IV infusion over 48 h). If the patient is not a good candidate for induction regorafenib and nivolumab (i.e. symptomatic from a large burden of disease), 5-FU and oxaliplatin can be added during cycle 1 at the treating physician's discretion. 39 Patients will continue with this regimen until disease progression, unacceptable toxicity, or development of serious intercurrent illness. Treatment will be performed on the scheduled day (±7-day treatment window). |
| Regorafenib+Nivolumab | EXPERIMENTAL | Parallel-cohort in adult participants with selected recurrent or metastatic tumors (HNSCC, ESCC, PDAC, BTC, and GBM/AA) who have been previously treated with one or more systemic therapy for the selected tumor indication. |
| Name | Type | Description |
|---|---|---|
| Regorafenib | DRUG | Oral multi-targeted tyrosine kinase inhibitor (TKI) which targets angiogenic (VEGF, TIE-2), stromal (PDGF-β), and oncogenic (RAF, RET and KIT) receptor tyrosine kinases |
| Nivolumab | BIOLOGICAL | human IgG4 monoclonal antibody inhibitor of PD-1 |
| Docetaxel | DRUG | Docetaxel is taxane-derivative chemotherapy drug, used in the treatment of early, locally advanced and metastatic breast cancer. It is an anti-microtubule agent. Other uses are in the treatment of non-small cell lung cancer, advanced stomach cancer, head and neck cancers, soft tissue sarcoma, ovarian cancer, metastatic prostate cancer, etc. microtubules, and simultaneously promotes assembly and inhibits disassembly of them |
| Paclitaxel | DRUG | Paclitaxel is one of several cytoskeletal drugs that target tubulin. Paclitaxel-treated cells have defects in mitotic spindle assembly, chromosome segregation, and cell division. Unlike other tubulin-targeting drugs, such as colchicine, that inhibit microtubule assembly, paclitaxel stabilizes the microtubule polymer and protects it from disassembly. Chromosomes are thus unable to achieve a metaphase spindle configuration. This blocks the progression of mitosis and prolonged activation of the mitotic checkpoint triggers apoptosis or reversion to the G0-phase of the cell cycle without cell division |
| Irinotecan | DRUG | Camptothecin, one of the four major structural classifications of plant-derived anti-cancerous compounds, is a cytotoxic alkaloid which consists of a pentacyclic ring structure containing a pyrrole (3, 4 β) quinoline moiety, an S-configured lactone form, and a carboxylate form. Irinotecan is activated by hydrolysis to SN-38, an inhibitor of topoisomerase I. This is then inactivated by glucuronidation by uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1). The inhibition of topoisomerase I by the active metabolite SN-38 eventually leads to inhibition of both DNA replication and transcription. |
| Trifluridine/Tipracil | DRUG | The drug consists of the cytotoxin trifluridine and the thymidine phosphorylase inhibitor (TPI) tipiracil. Trifluridine is incorporated into DNA during DNA synthesis and inhibits tumor cell growth. Trifluridine (TFT) is incorporated into DNA by phosphorylation by thymidylate kinase (TK) to TF-TMP; TF-TMP then covalently binds to tyrosine 146 of the active site of thymidylate synthase (TS) inhibiting the enzyme's activity. TS is vital to the synthesis of DNA because it is an enzyme involved in the synthesis of the deoxynucleotide, thymidine triphosphate (dTTP). Inhibition of TS depletes the cell of dTTP and causes accumulation of deoxyuridine monophosphate (dUMP), which increases the likelihood that uracil gets misincorporated into the DNA. |
| FOLFOX chemotherapy with oxaliplatin | DRUG | FOLFOX chemotherapy with oxaliplatin (85 mg/m2 IV), leucovorin (400 mg/m2 IV), 5-FU (400 mg/m2 IV bolus), and 5-FU (2400 mg/m2/day continuous IV infusion over 48 h). |
| Regorafenib, (Stivarga, BAY73-4506) | DRUG | Intake orally, starting with 3x 30 mg tablets every day (once daily.) for 21 days of every 28-day cycle (21 days on, 7 days off). If the starting dose is well tolerated dose can be escalated to 120 mg (4x30 mg tablets). |
| Nivolumab (Opdivo) | DRUG | 480 mg administered on Day 1 of each treatment cycle. |
Inclusion Criteria: 1. Adults (18 years or over) with metastatic or locally recurrent gastro-oesophageal cancer which: 1. has arisen in any primary gastro-oesophageal site (oesophago-gastric junction (GOJ) or stomach); and 2. is of adenocarcinoma or undifferentiated carcinoma histology; and ...
Regorafenib is an investigational small molecule being studied for the treatment of solid tumors, esophagogastric cancer, and gastro-oesophageal cancer. It is being evaluated in combination with other therapies, including nivolumab and chemotherapy regimens, in clinical trials for these oncology indications.
Regorafenib is a kinase inhibitor, belonging to the -nib class of drugs. It works by inhibiting multiple kinases involved in tumor growth and angiogenesis, though the specific molecular targets are not detailed here. Its kinase inhibition activity is the basis for its evaluation in solid tumor and gastrointestinal cancer trials.
Regorafenib is being developed by Bristol-Myers Squibb Company, which trades under the ticker BMY. The company is conducting clinical trials to evaluate the drug's safety and efficacy in various oncology indications, including solid tumors and gastro-oesophageal cancer.
Regorafenib is in Phase 3 clinical development. One Phase 3 trial, NCT04879368, has been completed, evaluating the drug in combination with nivolumab versus standard of care chemotherapy in gastro-oesophageal cancer. Additional Phase 2 trials have also been completed or are active.
Regorafenib has been studied in three clinical trials. NCT04704154, a completed Phase 2 trial in solid tumors with 175 participants. NCT04757363, an active Phase 2 trial in HER2-negative esophagogastric cancer with 39 participants. NCT04879368, a completed Phase 3 trial in gastro-oesophageal cancer with 462 participants.
Regorafenib is the drug name used in the clinical trials described. No alternative names for this drug have been mentioned in the available information. It is being studied under this name in combination with other agents such as nivolumab and FOLFOX chemotherapy.