Reading our newsletter will keep you up to date with last month’s news items on oncology drug development!
NEWS AND PUBLICATIONS
Older patients with acute myeloid leukemia (AML) are known to have a dismal prognosis, even after treatment with hypomethylating agents. DiNardo et al recently evaluated the effect of combined azacytidine and venetoclax treatment in an ongoing Phase Ib trial that enrolled previously untreated AML patients ineligible for standard induction therapy due to, among others, old age (≥75 years). At a median follow-up of 20.5 months, the median overall survival was 14.7 months vs 9.6 months in the combined treatment vs the control groups, respectively. The incidence of complete remission was significantly higher following combined treatment than with the control regimen (36.7% vs. 17.9%), as was the composite complete remission (66.4% vs. 28.3%). These results, published in the New England Journal of Medicine, in association with its acceptable safety profile, indicate that combined azacytidine and venetoclax therapy can change the treatment paradigm for older AML patients.
Automated rapid point-of-care cellular cancer diagnosis remains a challenge, particularly in the developing world, due to lack of medical infrastructure and specialists. To address this need, Min et al developed the first automated image cytometry system (CytoPAN) that allows same-day breast cancer diagnosis of scant cellular specimens obtained by fine needle aspiration of palpable mass lesions (Figure 1).
Extensive optimization and validation demonstrated CytoPAN’s capacity not only for diagnosis, but also for receptor subtyping in 1 hr. A subsequent prospective cohort study reported 100% accuracy for cancer detection, 96% accuracy for human epidermal growth factor receptor 2 subtyping, and 93% for hormonal receptors (ER/PR) subtyping. These results, published in Science Translational Medicine, put forward a novel, non-invasive, relatively affordable system for cancer detection that can potentially be used in low-resource areas.
- Siemens Healthineers acquired Varian Medical Systems for a $16.4 billion in a deal that aims to create a global leader in cancer care solutions. Under the agreed transaction, Healthineers will acquire all shares in Varian for $177.50 each in cash.
- Elli Lilly and Innovent Biologics announce global expansion of licensing agreement for sintilimab injection, an anti-PD-1 monoclonal antibody currently approved in China for relapsed/refractory classic Hodgkin’s lymphoma. Under the terms of the agreement, Innovent will receive an upfront payment of $200 million and will be eligible for up to $825 million in development and commercial milestones, while Lilly will obtain an exclusive license for the compound for geographies outside of China.
The Committee for Medical Products for Human Use (CHMP) had no meeting in August.
The FDA granted approval for:
- Carfilzomib and daratumumab (Kyprolis, Onyx Pharmaceuticals and Darzalex, Janssen Biotech), in combination with dexamethasone for adult patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy. Approval was based on the Phase I EQUULEUS trial, which reported on overall response rate (ORR) of 81% and a duration of response of 27.5 months after triple therapy, and on the Phase III CANDOR trial, which reported a median progression-free survival (PFS) of 15.8 months after carfilzomib and dexamethasone, whereas the PFS was not reached in the triple therapy arm at the time of assessment.
- Belantamab mafodotin-blmf (Blenrep, GlaxoSmithKline) for adult patients with relapsed/refractory multiple myeloma who have received at least 4 prior therapies, including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent. Approval was based on the Phase II DREAM-2 trial, which reported an ORR of 31%, with 75% of responders having a response duration ≥6 months.
- Tafasitamab-cxix (Monjuvi, MorphoSys), a CD19-directed cytolytic antibody, indicated in combination with lenalidomide for adult patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant. Approval was based on the Phase II L-MIND trial, which demonstrated an ORR of 55% with complete responses in 37% of patients.
- Guardant360 CDx assay (Guardant Health), the first liquid biopsy next-generation sequencing companion diagnostic test to identify patients with specific types of mutations of the epidermal growth factor receptor (EGFR) gene in a deadly form of metastatic non-small cell lung cancer (NSCLC).
- Pemetrexed (Teva Pharmaceuticals, Actavis Generics unit), in the form of injectable formulation, as a single agent for use in patients with locally advanced/metastatic non-squamous non-small cell lung cancer that has not progressed after four cycles of first-line platinum-based chemotherapy or for patients who received prior chemotherapy.
On 12 Aug 2020, the FDA finalized the guidance regarding enrolment of male patients in breast cancer clinical trials and the guidance regarding consequences for parties who failed to register a clinical trial or submit its results.
The first final guidance comes one year after the agency issued the draft version for comments and expands on its recommendation for sponsors to discuss their drug development plans early with the relevant agency product center. These discussions should cover the number of male patients who should be enrolled in clinical trials and the type of data that should be gathered for specific development programs. Additionally, the final guidance now recommends that sponsors including males in clinical trials for breast cancer drugs should conduct preclinical toxicology studies in both male and female animals.
The second final guidance clarifies the circumstances under which the agency’s centers may seek civil monetary penalties for noncompliance: first, a Preliminary Notice of Noncompliance Letter will be sent to the responsible party, giving a notice of 30 days for correction of potential violations. After this 30-day period, and if the violation has not been remedied, FDA will proceed to issue a Notice of Noncompliance, levy civil monetary penalties, issue and injunction, or even pursue criminal prosecution.