Reading our newsletter will keep you up to date with last month’s news items on oncology drug development!
NEWS AND PUBLICATIONS
Novel roles of macrophages in colon cancer
Macrophages typically represent a major component of the colorectal cancer (CRC) tumor mass, mainly promoting cell survival, proliferation, and dissemination. Interleukin-34 (IL-34) is a cytokine overproduced by CRC cells, whose functions are mediated by the macrophage colony-stimulating factor receptor (M-CSFR-1). Franze et al used flow cytometry techniques on several cell types isolated from normal adjacent mucosa of CRC patients to show that these cells express M-CSFR-1 and produce IL-34. Stimulation of these cell types with IL-34 enhanced expression of the markers of type II polarized macrophages CD163 and CD206, as well as production of IL-6, a cytokine known to promote CRC cell growth. Specific knockdown of IL-34 decreased IL-6 production and macrophage numbers, thus highlighting for the first time a positive role of IL-34 in CRC. Results were published in Nature Cell Death Discovery.
Potential of MALDI-TOF-based analysis for breast cancer diagnosis and surveillance
In recent years, techniques such as matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) based serum N-glycan analysis have gained renown for breast cancer diagnosis. In a study published in Nature Scientific Reports, Lee et al evaluated the possibility of expanding its application for breast cancer management and surveillance. Using a novel effective MALDI-TOF platform for breast cancer analysis termed IDsys RT, the authors identified and validated multiple N-glycan markers that are applicable for differentiating recurring breast cancer samples from non-recurring ones or healthy controls. These results highlight MALDI-TOF as a feasible technique for tracking molecular signatures of breast cancer and predicting recurrence.
- Sanofi will acquire Kiadis, a clinical-stage biopharmaceutical company developing innovative ‘off the shelf’ natural killer (NK) cell-based medicines for the treatment of life-threatening diseases. The two companies entered into a definitive agreement under which Sanofi will make a public offer to acquire Kiadis for EUR 5.45 per share, representing an aggregate adjusted equity value of €308 million.
- Merck will acquire VelosBio to help strengthen its cancer drug portfolio and reduce reliance on its blockbuster cancer therapy Keytruda. The acquisition is approximated at $2.75 billion in cash and planned to ne finalized by the end of 2020.
- Merck to acquire OncoImmune in an effort to add to it’s clinical programs in response to coronavirus-19 (COVID-19). Under the terms of the agreement, Merck, through a subsidiary, acquired all outstanding shares of OncoImmune for an upfront payment of $425 million in cash. In addition, OncoImmune shareholders will be eligible to receive sales-based payments and payments contingent on the successful achievement of certain regulatory milestones.
The Committee for Medical Products for Human Use (CHMP) adopted a positive opinion for:
- Pertuzumab and trastuzumab combination (Phesgo, Roche Registration), for the treatment of early and metastatic breast cancer. Phesgo will be available as a solution for injection (600 mg / 600 mg and 1200 mg / 600 mg).
- Tagraxofusp (Elzonris, Stemline Therapeutics), for the treatment of blastic plasmacytoid dendritic cell neoplasm. Elzonris will be available as a 1-mg/ml concentrate for solution for infusion. Biosimilars:
- Bevacizumab (Onbevzi, Samsung Bioepics), for the treatment of carcinoma of the colon or rectum, breast cancer, non-small cell lung cancer, renal cell cancer, epithelial ovarian, fallopian tube or primary peritoneal cancer, and carcinoma of the cervix
Extensions of indications:
- Carfilzomib (Kyprolis, Amgen Europe) in combination with daratumumab and dexamethasone, with lenalidomide and dexamethasone, or with dexamethasone alone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy.
The FDA granted approval for:
- The Sonalleve MR-HIFU system (Profound Medical) for the treatment of osteoid osteoma in the extremities. MR-guided High Intensity Focused Ultrasound (MR- HIFU) treatment is an image-guided technique whose clinical results support its probable benefit: efficacy was evaluated in a study of nine patients treated with MR- HIFU, without technical difficulties or serious adverse events. There was a statistically significant decrease in their pain scores within 4 weeks of treatment. No pain medication usage was achieved in 8 of 9 patients after 4 weeks.
- Naxitamab (Danyelza, Y-mAbs Therapeutics) in combination with granulocyte- macrophage colony-stimulating factor (GM-CSF) for pediatric patients one year of age and older and adult patients with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow demonstrating a partial response, minor response, or stable disease to prior therapy. Approval was based on two Phase 2 trials (Study 201 and Study 12-230), which reported an overall response rate (ORR) of 45% and 34%, respectively.
- Pembrolizumab (Keytruda, Merck) in combination with chemotherapy for the treatment of patients with locally recurrent unresectable/metastatic triple-negative breast cancer (TNBC) whose tumors express PD-L1 (CPS ≥10) as determined by the PD-L1 immunohistochemistry (IHC) 22C3 pharmDx (Dako North America, Inc.) as a companion diagnostic for selecting patients with TNBC for pembrolizumab. Approval was based on the Phase 3 KEYNOTE-355 trial, which reported a median progression-free survival (PFS) of 9.7 vs 5.6 months in the pembrolizumab plus chemotherapy vs the placebo arms.
- Durvalumab (Imfinzi, AstraZeneca) for an additional dosing option, 1,500 mg-fixed dose every four weeks, in the approved indications of unresectable Stage III non- small cell lung cancer (NSCLC) after chemoradiation therapy (CRT) and previously treated advanced bladder cancer. This new option is consistent with the initial dosing approved earlier this year in extensive-stage small cell lung cancer (ES-SCLC) and will be available to patients weighing >30 kg as an alternative to the approved weight-based dosing of 10 mg/kg every two weeks.
On 09Nov2020, the FDA issued the final guidance for enhancing diversity of clinical trial populations by promoting enrollment practices that would lead to clinical trials that better reflect the population most likely to use the drug if the drug is approved, primarily through broadening eligibility criteria. The agency’s recommendations are focused on designing and executing clinical trials of drugs and biologics that include people with different demographic characteristics (e.g., sex, race, ethnicity, age, location of residency) and non-demographic characteristics (e.g., patients with organ dysfunction, comorbid conditions, and disabilities; those at weight range extremes; and populations with diseases or conditions with low prevalence). The guidance aims to provide recommendations for how sponsors can increase enrollment of underrepresented populations in their clinical trials.