China
Africa
Explore chapters and articles related to this topic
Small-Molecule Targeted Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
In 2017 copanlisib was granted priority review status by the FDA for the treatment of relapsed follicular lymphoma in adult patients who had received at least two prior therapies, and the agent was granted Accelerated Approval for this indication based on the results of the CHRONOS-1 Phase II trial. Copanlisib is still being evaluated in late-stage clinical trials for the treatment of marginal-zone-B-cell-lymphoma and non-Hodgkin’s lymphoma.
Non-Hodgkin Lymphoma
Published in Tariq I. Mughal, Precision Haematological Cancer Medicine, 2018
Chemoimmunotherapy have now been found to significant prolong overall survival, though resistance can be a challenge. Some concerns, however, were raised about potential flares of viral hepatitis in patients with associated hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. It is therefore important to monitor such patients carefully and consider pre-emptive therapy with appropriate antiviral drugs. Long-term R maintenance therapy has also been studied and found not to improve survival; rather, it was associated with unacceptable toxicity. Resistance to rituximab is not uncommon and several second- and third-generation anti-CD20 antibodies have entered the clinics. Some of these, for example ofatumumab, are simply modifications made to enable a better and tighter ‘fit’ to CD20 to help make them more efficient. Obinutuzumab (GA101), a type II anti-CD20 monoclonal antibody, was licensed in 2016 to be used in combination with bendamustine for patients with rituximab-refractory indolent NHLs, and is being tested for newly diagnosed patients with FL. In September 2017, a selective PI3-kinase inhibitor, copanlisib (Bayer), was approved for persons with relapsed FL, who had previously received at least two lines of treatment.
Advances in the pharmacotherapeutic options for primary nodal peripheral T-cell lymphoma
Published in Expert Opinion on Pharmacotherapy, 2021
Anna Wolska-Washer, Piotr Smolewski, Tadeusz Robak
Copanlisib (BAY 80–6946, Aliqopa®, Bayer) is an intravenous PI3K- α/δ-isoforms inhibitor that was approved by the FDA in 2017 for the treatment of relapsed/refractory follicular lymphoma [72]. A phase 2 study of copanlisib in relapsed/refractory hematological malignancies showed the ORR of 21.4% in patients with PTCL [73]. The most common treatment-emergent AEs overall were hyperglycemia (59.5%), hypertension (54.8%), fatigue (48.8%), and diarrhea (40.5%). Copanlisib is currently being studied in PTCL in phase 1/2 trials in combination therapies with gemcitabine (ClinicalTrials.gov Identifier: NCT03052933) and pembrolizumab (ClinicalTrials.gov Identifier: NCT02535247). The phase 1/2 COSMOS study was designed to investigate the safety and efficacy of copanlisib with gemcitabine (Cop/Gem), as well as the relationship between the mutational status of 100 genes related to PTCL pathogenesis [74]. The preliminary results in 28 patients showed the ORR of 71.4% and CR of 32.1%. This combination therapy was found to be more efficient in AITL patients, with an ORR of 77.8% and CR of 55.6%. The median DOR was 8.2 months. The most frequent severe treatment-emergent AEs were hyperglycemia (57%), neutropenia (45%), thrombocytopenia (37%), and hypertension (19%). Eleven patients discontinued the planned six cycles of Cop/Gem due to disease progression. Patients responsive to the treatment presented specifically with IDH2, RHOA, and TSC2 mutated genes. The authors concluded that further studies are needed to find biomarkers for better prediction of clinical response.
Copanlisib for the treatment of adults with relapsed follicular lymphoma
Published in Expert Review of Clinical Pharmacology, 2020
Massimo Magagnoli, Carmelo Carlo-Stella, Armando Santoro
Apart from targeting all four class I isoforms rather than only a single one, copanlisib differs from idelalisib and duvelisib also because it can be administered intravenously. The intravenous and almost weekly administration may make copanlisib less manageable than its oral competitors. On the other hand, this allows greater patient control, managing to better monitor the side effects of the drug. In this regard, we recall what happened with idelalisib in patients with chronic naive lymphatic leukemia, with the deaths due to toxicity that stopped these studies by the FDA for months. On the other hand, this contributes to fewer and less severe gastrointestinal toxicities with copanlisib compared with the other two drugs. Moreover, copanlisib appears to be a valuable agent in patients with progression of disease within 24 months of completing induction chemoimmunotherapy (POD24) with more of 20% of CR in these subjects. The combination of copanlisib with other small molecule inhibitors, immunotherapy and/or chemotherapy will hopefully improve upon clinical outcomes and provide durable response rates (Table 6). First of all, results from the CHRONOS 3 and CHRONOS-4 (R-CHOP or rituximab–bendamustine ± copanlisib) trials will provide evidence of these combinations in FL.
Targeting the B-cell receptor pathway: a review of current and future therapies for non-Hodgkin’s lymphoma
Published in Expert Opinion on Emerging Drugs, 2018
Thomas D. Rodgers, Patrick M. Reagan
Side effects remain a challenge, both acutely and after prolonged use. Among the current four approved agents, there are distinct side effects with both PI3K and BTK inhibition. Idelalisib treatment side effects range from nausea and diarrhea to significant pneumonitis, colitis, and transaminitis [27]. Copanlisib has observed similar side effects with perhaps decreased gastrointestinal side effects [28]. Finally, during ibrutinib clinical trials, adverse effects included nausea, fatigue, rare grade 3 and 4 hemorrhage as well as an increased incidence of atrial fibrillation [11]. Dose reduced regimens have been, and are being, investigated to improve drug tolerability both with short and long-term use. Resistance has already developed and is clinically recognized after treatment with idelalisib and ibrutinib [29]. Research aims to identify the specific mutations and establish new agent combinations to overcome, delay, or stop the formation of drug resistance.