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Oncology Highlights - July 2019

Stay informed on the latest news within oncology drug development! Subscribe to our newsletter to keep up to date with last month's science, industry and regulatory oncology highlights!

Enjoy reading! - The SMS-oncology team

 

Publications

Soft drinks and fruit juice are both associated with increased risk of cancer

In a large prospective study, a cohort of over 100,000 people, followings were for an average of 5 years. The most important conclusion is that the intake of sugary drinks is associated with an increased risk of cancer, about 18% higher risk if you drink 100 ml per day. It is remarkable that this counts both for soft drinks and for fruit juice. Another remarkable takeaway is that artificial sweeteners were not associated with higher cancer risk. It is important to note that this study only shows an association, a causal link between sugars in your drinks and the development of cancer. There might be more factors involved where sugary drinks are only a bystander. Still, this research paper in the BMJ may be enough reason to have a closer look at your dietary intake. (Image source: BMJ)

Enhanced CAR – T cell efficacy in solid tumors through vaccine boosting

Chimeric antigen receptor (CAR)-T cell immunotherapy is known for its wide success in treating various hematologic malignancies, however, showed limited efficacy in solid tumors in the past, due to the difficulty of targeting functional engineered T cells to the tumor site. Ma et al. designed a vaccine strategy to improve the efficacy of CAR-T cells by re-stimulating the CAR directly within the native lymph nodes. Injected amphiphilic CAR-T ligands (amph-ligands) trafficked to lymph nodes, decorated the surfaces of antigen-presenting cells, and primed CAR-Ts in the microenvironment. This triggered massive CAR-T cell activation, expansion, and donor cell polyfunctionality. As a result, enhanced antitumor efficacy was seen in several immunocompetent mouse tumor models. This simple non-human leukocyte antigen strategy shows promise in boosting any existing CAR-T cell design, highlighting its wider relevance for advancing solid tumor therapy. Results were presented in Science. (Image source: Ma et al., Science)

Prolonged PFS in solid tumors with NEO-PV-01

Personalized neoantigens such as NEO-PV-01 can improve the efficacy of checkpoint inhibitor therapy in patients with solid tumors. In an ongoing phase Ib trial, NEO-PV-01 in combination with nivolumab led to consistently prolonged PFS in patients with metastatic melanoma (median PFS not reached at 13.4 months). T-cell responses were antigen-specific for 12/14 (86%) of the peptides tested. These topline data highlight a new approach to broaden the benefits of checkpoint inhibitor therapy in improving patient outcomes (Hu-Lieskovan et al, Cancer Res).

Industry

Oncology biotech/pharma had no summer break this July:

  • Global pharma AbbVie acquired Seattle-based Mavupharma a private company developing novel treatments that target the STimulator of INterferon Genes (STING) pathway. The lead candidate MAVU-104, a small molecule STING inhibitor, allows for highly controlled enhancement of STING signalling in tumors without the need for injections. Financial terms of the transaction were not disclosed.
  • Boehringer Ingelheim acquired AMAL Therapeutics SA, a private Swiss biotechnology company focused on immuno-oncology advancing therapeutic petide/protein-based vaccines derived from their first-in-class proprietary KISIMA® platform. The total transaction could amount up to €325M, comprising an upfront payment and milestones, plus up to €100M if certain commercial milestones are hit.
  • Jazz Pharmaceuticals acquires pre-clinical pan-RAF inhibitor program from Redx Pharma intended to potentially treat RAF and RAS mutant tumors. Under the terms of the agreement, Jazz will make an upfront cash payment of $3.5M to Redx and up to $203M in milestones, as well as tiered royalties on future net sales.
  • BioNTech raises $325m to advance individualized immuno-oncology pipeline: The $325m Series B financing obtained constitutes one of the largest single private funding events in European history and will help boost BioNTech’s pipeline of individualized mRNA-based products, innovative CAR-T cells, novel checkpoint immunomodulators, targeted cancer antibodies, and small molecules.
  • Former Lilly executive Christi Shaw as CEO of Kite Pharma: The international biotechnology company Gilead, appointed Christi Shaw, the former executive in charge of Eli Lilly’s drug division, as the CEO of Kite Pharma, the unit focused on the development of CAR-T-cell therapies for cancer treatment. This has personal relevance for Christi Shaw, whose sister died of multiple myeloma in 2016.
  • Kronos Bio raises $105M for discovery of compounds modulating undruggable targets: The mega Series A round will help expand two preclinical programs of Kronos’ platform called Small Molecule Microarray (SMM) for development of first-in-class anti-cancer therapies that modulate historically undruggable targets (e.g. transcription factors).

EMA / FDA

EMA

The Committee for Medical Products for Human Use (CHMP) adopted a positive opinion for:

  • Empliciti (elotuzumab), in combination with pomalidomide and low-dose dexamethasone, for treatment of patients with relapsed/refractory multiple myeloma (MM) who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor, and have demonstrated disease progression on the last therapy. In the US, the drug is approved for this indication, in combination with pomalidomide and low-dose dexamethasone, and for MM patients who received 1-3 prior therapies, in combination with lenalidomide and dexamethasone.
  • Lonsurf (trifluridine/tipiracil), as monotherapy for the treatment of metastatic gastric cancers (including adenocarcinoma of the gastroesophageal junction) in adult patients who previously received ≥2 systemic treatment regimens. In the pivotal phase III trial TAGS, Lonsurf demonstrated significant improvement in overall survival (OS,5.7 vs 3.6 months) compared with placebo plus best supportive care. Remarkably, a 31% risk reduction of death was observed with Lonsurf.
  • Keytruda (pembrolizumab), in combination with the tyrosine kinase inhibitor Inlyta (axitinib), as first-line treatment for advanced renal cell carcinoma. This recommendation is based on findings from the pivotal phase III KEYNOTE-426 trial, which demonstrated significant improvements in median OS (89.9% vs 78.3%), progression-free survival (PFS, 15.1 vs 11.1 months) and objective response rate (ORR, 59.3% vs 35.7%) for Keytruda in combination with axitinib compared with sunitinib.

FDA

The FDA granted approval for:

  • Xpovio (selinexor, KaryoPharm Therapeutics), a nuclear export inhibitor, in combination with dexamethasone for the treatment of relapsed or refractory MM in adult patients who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody. An accelerated approval was given based on response rate and represents the first and only approval of a nuclear export inhibitor given thus far by the FDA for any indication.
  • Ruxience (rituximab-PVVR, Pfizer), a biosimilar of Rituxan (rituximab), for the treatment of adult patients with non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, and granulomatosis with polyangiitis and microscopic polyangiitis. The approval was granted based on the review of a comprehensive data package, which demonstrated biosimilarity of Ruxience to the reference product.

In addition to approvals, FDA granted orphan drug designation (ODD) or breakthrough to several products to progress their development. These include:

  • Imfinzi (durvalumab, AstraZeneca), in combination with standard-of-care etoposide and platinum-based chemotherapy, for treatment of small cell lung cancer (SCLC). The ODD was based on the clinically meaningful improvement in OS of patients from the phase III CASPIAN trial.  
  • Menin-MLL (Kura Oncology), a selective menin-mixed lineage leukemia inhibitor KO-539, for treatment of acute myeloid leukemia (AML). The ODD was based on preclinical data with menin-MLL, which reported successful inhibition of MLL fusion proteins that play a crucial role in leukemic transformation.
  • MB-102 (CD123 CAR T cell, Mustang Bio), for the treatment of AML. A first-in-human phase I dose-escalation clinical trial is currently ongoing.
  • Keytruda (pembrolizumab) plus Lenvima (lenvatinib) : Merck's (MSD outside the US / Canada) PD1 inhibitor, in combination with Lenvima, the orally available kinase inhibitor discovered by Eisai, were granted Breakthrough Therapy designation for the potential first-line treatment of patients with advanced unresectable hepatocellular carcinoma not amenable to locoregional treatment.