News and Publications
COVID-19 and cancer – A Chinese nationwide analysis: In this study, Liang et al evaluated the effect of laboratory-confirmed 2019 coronavirus disease (COVID-19) on cancer patients from a national prospective cohort. Overall, 25% of patients with cancer and COVID-19 had received chemotherapy/surgery within the past month and 75% were cancer survivors in routine follow-up after primary resection. Cancer patients had a significantly higher risk of severe events (defined as intensive care unit admissions requiring invasive ventilation, or death) than patients without cancer (39% vs 8%), results confirmed by physician evaluation (50% vs 16%). Patients who underwent chemotherapy in the past month had a higher risk of clinically significant events than those who did not (75% vs 43%). Logistic regression revealed that cancer patients had a significantly lower median time to severe events (13 vs 43 days), with the only independent risk factor being old age. These crucial results, published in Lancet Oncology, highlight the impact of COVID-19 on cancer patients.
Tim-3 enhances HCC growth by blocking NK cell function: While conventional and liver-resident natural killer (cNK and LrNK) cell subsets are present in hepatocellular carcinoma (HCC), their role in HCC development is unclear. Tan et al reported that both cell subsets, whose levels were found significantly decreased in HCC, highly overexpressed the T-cell immunoglobulin and mucin domain-containing protein 3 (Tim-3), which in turn suppressed their cytokine secretion and activity. Mechanistically, phosphorylated Tim-3 inhibited downstream signaling, resulting in malfunctioning of both tumor-infiltrating NK cell subsets; conversely, Tim-3 blockade delayed HCC growth in an NK-cell-dependent manner. This study, published in Cancer Research, is the first to report the presence/dysfunction mechanism of tumor-infiltrating cNK and LrNK cells in HCC, thus providing new options for immune checkpoint targeting.
- LSP closes largest European life sciences fund at the $600 million hard cap, the largest fund ever raised for life sciences ventures. With a total of $1.1 billion to invest across public mandates, LSP has chosen to support European private companies developing new medications or medical technologies that turn cutting-edge scientific innovations into real-world healthcare solutions.
- Gilead Sciences acquires Forty Seven, for $4.9 billion or $95.50 per share in cash, and its investigational lead product candidate, the monoclonal antibody magrolimab, currently in clinical development for diseases including myelodysplastic syndrome, acute myeloid leukemia, and diffuse large B-cell lymphoma. The acquisition will strengthen Gilead’s strategic focus in oncology.
- Alopexx Oncology enters exclusive license agreement with Beijing Shenogen Pharma Group to develop and commercialize DI-Leu 16-IL2 in China and other parts of Asia. Alopexx will receive an upfront undisclosed payment, as well as development and commercial milestones/royalties on sales.
The Committee for Medical Products for Human Use (CHMP) adopted a positive opinion for:
- Isatuximab (Sarclisa, Sanofi-Aventis), for treatment of relapsed/refractory multiple myeloma in combination with pomalidomide and dexamethasone (Isa-PD), for adult patients with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor. Approval was based on the Phase III trial ICARIA-MM, whose results reported a median progression-free survival of 11.53 months after Isa-PD vs 6.47 months after PD alone.
Extensions of indications:
- Bretuximab vedotin (Adcetris, Takeda Pharma) in combination with cyclophosphamide, doxorubicin and prednisone, for treatment of adult patients with previously untreated systemic anaplastic large cell lymphoma.
The FDA granted approval for:
- Durvalumab (Infinzi, Astra Zeneca) combined with etoposide and either carboplatin or cisplatin as first-line treatment of patients with extensive-stage small cell lung cancer (ES-SCLC). Approval was based on the Phase III CASPIAN trial, whose results reported a median overall survival of 13.0 months vs 10.3 months in the durvalumab plus chemotherapy arm vs chemotherapy alone.
- Nivolumab plus ipilimumab (Opdivo and Yervoy, Bristol Myers Squibb), for HCC treatment in patients previously treated with sorafenib. This accelerated approval was granted based on the Phase I/II CheckMate-040 trial, whose results reported on overall response rate of 33% after a minimum follow-up of 28 months.
- Isatuximab-irfc (Sarclisa, Sanofi-Aventis), for the same indication as the EMA (see above).
- Trastuzumab-dttb (Ontruzant, Samsung Bioepis), a biosimilar referencing Herceptin (trastuzumab), as a 420-mg multi-dose vial, as adjuvant treatment of HER2-overexpressing breast cancer, metastatic breast and gastric cancers, and gastroesophageal junction adenocarcinoma in patients who have not received prior treatment for metastatic disease
- CINtec PLUS (Roche), as the first biomarker-based cytology test for women whose primary cervical cancer screening results are human papillomavirus-positive. This is the first test to help simplify clinical decision making by providing crucial information.
The FDA also granted breakthrough therapy designation to the following drugs/devices to advance their development:
- JNJ-6372 (Janssen), for patients with metastatic non-small cell lung cancer. JNJ-6373 is an endothelial growth factor receptor (EGFR)-mesenchymal epithelial transition factor (MET) bispecific antibody that targets activating and resistant EGFR and MET mutations and amplifications.
- Elecsys GALAD score (Roche), an algorithmic score aimed to support clinicians in diagnosing hepatocellular carcinoma (HCC) in an early stage by combining gender and age with biomarker results. The score is a relevant tool in early HCC diagnosis, which was reported to increase patient survival rates to over 70%.
The new guidelines, whose updated versions were published by the FDA and EMA on 27Mar2020, provide the following major recommendations on the conduct of clinical trials during the COVID-19 pandemic. The EMA guidance should be applied in conjunction with each specific national guidance/legislation, which may take priority in the respective country.
- Sponsors should assess the potential impact on the safety of the trial on a case-by-case basis, perform a dedicated risk assessment, modify trial conduct accordingly (e.g., continuation of trial recruitment, use of investigational medicinal product [IMP] for already recruited patients, updates in/additional safety monitoring) and inform all participants on the decisions taken.
- Sponsors, after consulting with investigators and, if required, with Institutional Review Boards (IRBs)/Independent Ethics Committees (IECs), may decide that a subject’s safety would be best served by continuing/discontinuing IMP use/trial participation.
- Sponsors should assess whether alternative methods for safety evaluations could be implemented when necessary and feasible. Additionally, in deciding to continue/discontinue IMP use, sponsors should consider whether the subject safety can be ensured by implementing the alternative approach.
- COVID-19 screening procedures mandated by the healthcare system in which a clinical trial is being conducted do not need to be reported as an amendment to the trial protocol (unless if applicable as part of a new research objective).
- If planned on-site monitoring visits are not possible, sponsors should optimize the use of central and remote monitoring programs to maintain oversight of clinical sites. However remote source data verification (e.g. providing sponsor with copies of medical records or remote access to electronic medical records) is currently not allowed in most EU Member States as it might infringe trial participants’ rights.
- Sponsors are encouraged to engage with regulatory authorities as soon as possible upon identifying emergent protocol changes/possible deviations as a result of COVID-19. Changes to the protocol necessary to minimize/eliminate immediate hazards or protect the well-being of subjects may be implemented without review board approval or before filing an amendment, but are required to be reported afterwards. Both agencies encourage sponsors to work with their review boards to prospectively define procedures to prioritize reporting of deviations that may impact subject safety.
- Due to possible changes in study visit schedules, missing visits, or patient discontinuations, it will be imperative to capture specific information in the case report that details the basis of missing data, including the relationship to COVID-19.
Both agencies highlight the relevance of clinical trials for discovery of novel anti-cancer treatments, especially considering the compounding effects of COVID-19 on patient safety, thus underlining the necessity for continuing ongoing trials evaluating therapies that address high unmet needs.
The guidelines also provide specific recommendations to be detailed in the clinical study report:
- Contingency measures implemented to manage trial conduct during trial disruption as a result of COVID-19 control measures.
- A listing of all participants affected by COVID-19 (by unique number identifier and investigational site), with a description of how the subject’s participation was altered.
- Analyses/discussions addressing the impact of implemented contingency measures on the safety and efficacy results reported.
The new draft guidance published on 09Mar2020 by the FDA provides recommendations for inclusion of older (>65 years) patients in oncology clinical trials. The guidance highlights the necessity of including in clinical trials patient populations representative of the intended real-world populations that may receive the therapy being tested, to achieve an unbiased estimate of treatment effect. This recommendation also extends to early-phase clinical trials, to obtain safety information that can subsequently be used to guide better study designs.