News & Publications
The observed effectiveness of immune checkpoint inhibitors (ICIs) for the treatment of melanoma does not extend to all patients. Kim et al found that the epigenetic modifier protein arginine methyltransferase 5 (PMRT5) promotes immunosuppression in melanoma via two different mechanisms: interfering with the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway and inhibiting transcription of the gene encoding the nucleotide-binding oligomerization domain-like receptor family caspase recruitment domain containing 5 (NLRC5), a protein that promotes major histocompatibility complex (MHC) class I presentation. Consequently, PRMT5 inhibition enhanced ICI efficacy in multiple preclinical mouse models of melanoma. The results, published in Science Translational Medicine, highlight the combination its potential for clinical applications.
Early cancer diagnosis substantially benefits treatment efficiency and responsiveness, thus offering the patient a better chance of long-term survival. In a real-time exploratory trial, Lennon et al evaluated in a large population of 10,006 women with no history of cancer the feasibility and safety of incorporating a multicancer blood test into the routine clinical care. Over a 12-month period, the minimally invasive blood test detected 26 cancers of different types. Subsequent positron emission tomography-computed tomography (PET-CT) imaging led to surgical removal of nine of the detected cancers. Blood test use did not lead to a large number of futile follow-up procedures. The precise localization of several types of cancers in individuals with no cancer history and, in some cases, the enabling of treatment with curative intent, paves the way forward for new routine clinical care. The results were published in Science.
- Forbion announces first close of Forbion Growth Opportunities Fund at $208 million, focused on investing in late-stage European biotech companies developing novel therapies in oncology and other medical fields. Returning investors to the new Forbion fund include Pantheon, KfW Capital and the European Investment Fund. New investors include Eli Lilly, Horizon Therapeutics, Belgian Growth Fund and New Waves Investments.
- Amgen announces additional investment in BeiGene of approximately $421 million, which maintains Amgen’s current pro rata ownership of BeiGene at approximately 20.3%. This additional investment reflects Amgen’s confidence in the progress the companies are making in their ongoing oncology collaboration in China, the world’s second largest pharmaceutical market.
The Committee for Medical Products for Human Use (CHMP) adopted a positive opinion for:
- Avapritinib (Ayvakyt, Blueprint Medicines), a protein kinase inhibitor intended for the treatment of adult patients with unresectable or metastatic gastrointestinal stromal tumors (GIST) harboring the platelet-derived growth factor receptor alpha (PDGFRA) D842V mutation.
- Belantamab mafodotin (Blenrep, GlaxoSmithKline), a humanized IgG1 monoclonal antibody against the B-cell maturation antigen, the first antibody-drug conjugate recommended for the treatment of relapsed and refractory multiple myeloma.
- Acalabrutinib (Calquence, AstraZeneca), a protein kinase inhibitor of Bruton’s tyrosine kinase intended for the treatment of previously untreated chronic lymphocytic leukemia CLL) alone/combined with obinutuzumab and as monotherapy for treatment of CLL patients who received at least one prior therapy.
- Bevacizumab (Equidacent, Centus Biotherapeutics Europe Limited), a monoclonal antibody directed against vascular endothelial growth factor (VEGF) and a biosimilar of the reference product Avastin, 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.
- Arsenic trioxide medac (medac Gesellschaft für klinische Spezialpräparate mbH), for the treatment of acute promyelocytic leukemia.
Extensions of indications:
- Ibrutinib (Imbruvica, Janssen-Cilag International NV) s a single agent or in combination with rituximab or obinutuzumab is indicated for the treatment of adult patients with previously untreated CLL.
- Durvalumab (Imfinzi, AstraZeneca) in combination with etoposide and either carboplatin or cisplatin is indicated for the first-line treatment of adults with extensive-stage small cell lung cancer.
The FDA granted approval for:
- Decitabine and cedazuridine (Inqovi, Astex Pharmaceuticals), an oral hypomethylating agent for treatment of adult patients with myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). Approval was based on the Phase III ASCERTAIN trial, which demonstrated the exposure equivalence of total 5-day dosing of the oral formulation compared with intravenous (IV) decitabine in the study patient population.
- Brexucabtagene autoleucel (Tecartus, Kite, a Gilead Company) the first and only approved chimeric antigen receptor (CAR) T cell therapy for the treatment of adult patients with relapsed or refractory mantle cell lymphoma. Approval was based on the Phase II ZUMA-2 trial, in which 87% of patients responded to a single infusion, including 62% of patients achieving a complete response.
- VENTANA HER2 diagnostic test (Roche), a dual DNA probe cocktail assay for the detection of the HER2 biomarker in breast cancer and as a companion diagnostic for Herceptin (trastuzumab) therapy.
The FDA also granted breakthrough therapy designation to the following drug to advance its development:
- MK-6482 (Merck), a novel hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor, for the treatment of patients with von Hippel-Lindau disease-associated renal cell carcinoma (RCC), with nonmetastatic RCC tumors less than three centimeters in size, unless immediate surgery is required
On 10 July 2020, the FDA finalized four guidances on broader cancer trial eligibility criteria considerations for individuals with specific clinical conditions or for pediatric individuals.
- The guidance regarding patients with brain metastases provides detailed recommendations for inclusion of patients with treated/stable/active brain metastases and those with leptomeningeal metastases. Considerations for exclusion criteria area also reviewed.
- The updated guidance for including patients with human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) infections specifies consideration of CD4+ T cell counts and history of any AIDS-defining opportunistic infections for patients with HIV, whereas participation of patients with HBV and HCV should be guided by the same liver-related laboratory eligibility criteria as the general population, except where a known hepatic/biliary cancer affects these values.
- The guidance regarding patients with organ dysfunction or prior/concurrent malignancies addresses inclusion of patients with renal dysfunction, advising that eligibility criteria use glomerular filtration rate rather than absolute serum creatinine levels. Patients with cardiovascular dysfunction may be included, depending on risk for heart failure/prolongation of the corrected Q-T interval in the cardiac cycle.
- The guidance for inclusion of pediatric patients in cancer clinical trials specifies that pediatric oncology experts should be involved in designing, approving, and overseeing trials that plan to enroll pediatric patients. Where possible, in vitro evidence, including in silico studies may be adequate to support inclusion of pediatric patients, says the guidance.