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Oncology Highlights - June 2018

Oncology Highlights - June 2018

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

Novel approach: Complete response in breast cancer with adoptive cell therapy based on cancer mutanome

Researchers at the National Cancer Institute (NCI) developed a new immunotherapeutic approach that resulted in a complete remission in a breast cancer patient who was unresponsive to all other treatments. The novel approach is modified form of adoptive cell transfer (ACT) where autologous tumor-infiltrating lymphocytes (TILs) selected via high-throughput methods specific to target tumor cell mutations. Comparing the DNA and RNA expression of patient’s tumor tissue versus normal tissue, researchers identified 62 tumor specific somatic mutations. Subsequently, investigators identified TILs that recognize four of the tumor-unique proteins. These cells were expanded and transferred back into the patient. The treatment was also combined with a checkpoint inhibitor (pembrolizumab) to strengthen the response of infused T cells against the immunsupression in the tumor microenvironment. After the novel combination therapy, the tumor disappeared and has not returned in more than 22 months follow-up period. Similar results have been observed with mutation-targeted TIL treatment for patients with other epithelial cancers, including liver cancer and colorectal cancer in the same trial. The study is published in Nature Medicine.

Stalking the dormant cancer cells

In the recent history of cancer therapy, focus has been on attacking the mechanisms used by rapidly dividing cells through chemotherapy, radiotherapy, surgery and hormone therapy. Aiming to completely eradicate the aggressive tumors and avoid metastasis, scientists are now studying the dormant tumor cells that might be responsible for the inevitable recurrences. Due to lack of animal models and their specific nature, it has been difficult to study quiescent cells so far. Cancer cell biologists at Icahn School of Medicine at Mt. Sinai and others have been teasing out the molecular mechanisms that underpin the dormancy to understand the expression patterns (e.g. PERK protein) and niches that permit dormancy (expression of proteins such as BMP-4, BMP-7, TGF-β2 and TSP-1, andp38a/b pathway). Following the increasing recognition for dormancy research, the first meeting on Cancer Dormancy and Residual Disease took place 19–22 June in Montreal. The field is likely to see treatments reversing the wake of the tumor cells or targeting directly the silence cells.

Get your vitamin D levels up to lower the risk of breast and colorectal cancers

Vitamin D is known to maintain bone health and optimal immune system function. Previous studies hypothesized the positive correlation between low levels of vitamin D levels with increased cancer risk, however clinical trials thus far have not shown an effect probably due to study size, differences in supplementation duration, and compliance. Two recent studies analyzing participant-level data collected before cancer diagnosis show that the higher level of circulating serum vitamin D concentrations is associated with reduced risk of colorectal and breast cancer. For the colorectal cancer study, 17 prospective cohorts including data from 5,700 colorectal cancer cases and 7,100 controls from the United States, Europe, and Asia were used through standardized criteria. Compared to participants with vitamin D concentrations sufficient for bone health, those with deficient concentrations of vitamin D had a 31% higher risk of colorectal cancer during averaged 5.5 years follow-up. For the breast cancer study, examination of the pooled data from two randomized clinical trials with 3,325 participants and a prospective study involving 1,713 participants revealed the same trend. Participants with higher Vitamin D serum levels possessed one-fifth the risk of breast cancer compared to those with lower. Studies were published in Journal of the National Cancer Institute and PLOS ONE respectively.

 

Industry

European commission announces the new program: Horizon Europe

European Commission announces the new program: Horizon Europe, while its predecessor H2020 is approaching its end. Funding over 18,000 projects with a total amount of nearly €31 billion, H2020 has been a major positive impact in Europe as the recent interim analysis indicated. The budget of the next program for 2021-2027 is proposed to be €100 billion and going to implement the following main changes: 1-) Forming a European Innovation Council to bring high potential and breakthrough technologies from bench to bedside and help innovative start-ups to scale up their ideas. 2-) Focusing on societal challenges and industrial competitiveness that will range from cancer therapies to clean transport and to be designed together with citizens, stakeholders, the European Parliament and Member States. 3-) Maximizing the innovation potential across the EU, the countries lagging behind will get support to go up the ladder of excellence. 4-) Openness will be encouraged with open access to publications and data. 5-) Promoting collaborations between other EU programs by streamlining the number of partnerships and creating inter-operational links. An agreement on the proposed next long-term budget is expected to be established in 2019 to provide a seamless transition between the H2020 and H-Europe.

iTeos secures $75million in Series B financing for IO pipeline

iTeos Therapeutics, a Belgian biotech designing immune therapies to treat cancer raised $75 million in their Series B financing round. Attracting four new life sciences investors including US based venture capital firm MPM Capital, HBM Partners, 6 Dimensions Capital and Curative Ventures, the company plans to start clinical trials of two candidate drugs and to launch offices in the US through this boost. iTeos’ first drug candidate is a best-in-class Adenosine A2A antagonist, planned to be tested in Phase I trial in H2 2018. The second candidate, an anti-TIGIT antibody, is planned to be studied in clinic in 2019. Both candidates promote "cold" tumors to turn to "hot” tumors through modulating the TME profile which makes them attractive for combination therapies as they have the potential to  increase susceptibility to existing immune therapies. The positive progress in preclinical data on safety and efficacy was presented in AACR 2018. The funding news is a great recovery from their earlier IDOi setback.

 

EMA/FDA

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

  • Two CAR-T cell therapies; Tisagenlecleucel (Kymriah, Novartis) and axicabtagene ciloleucel (Yescarta, Gilead) for the treatment of acute lymphoblastic leukaemia (ALL) and diffuse large B-cell lymphoma (DLBCL) respectively. Both ATMPs are chimeric antigen receptor (CAR-T) therapies and also the first medicines supported through EMA’s PRIority MEdicines (PRIME) scheme to receive a positive opinion. Accompanied with these approvals,  committee also extended the therapeutic indication for RoActemra (tocilizumab) to include the treatment of CAR-T-cell-induced cytokine release syndrome (CRS).
  • Daunorubicin / cytarabine (Vyxeos, Jazz Pharmaceuticals) for the treatment of acute myeloid leukaemia. This orphan medicine is a single product containing two medications: daunorubicin (an anthracycline) and cytarabine (an antimetabolic agent).

The CHMP adopted a positive recommendation on re-examination of:

  • Neratinib (Nerlynx, Puma Biotechnologies) for the adjuvant treatment of adult patients with breast cancer, after re-examining its negative opinion on the risk-benefit ratio -the side effects on the digestive system (diarrhea)- for this medicine. Committee confines the benefits to patients that are HER2+ and hormone positive. Neratinib is already approved by FDA in 2017.

The CHMP recommended extensions of indications for:

  • Lenvatinib (Lenvima, Eisai) as monotherapy for the treatment of adult patients with advanced or unresectable hepatocellular carcinoma (HCC) who have received no prior systemic therapy.
  • Nivolumab (Opdivo, Bristol-Myers Squibb) as monotherapy is indicated for the adjuvant treatment of adults with melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection.
  • Tocilizumab (RoActemra, Roche) for the treatment of chimeric antigen receptor (CAR) T cell-induced severe or life-threatening cytokine release syndrome (CRS) in adults and paediatric patients 2 years of age and older. This immunosuppressive drug, mainly for the treatment of rheumatoid arthritis and systemic juvenile idiopathic arthritis, a severe form of arthritis in children.

FDA:

The FDA granted regular approval for:

  • Venetoclax (Venclexta, AbbVie and Genentech) for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), with or without 17p deletion, who have received at least one prior therapy. Due to rapid reduction in tumor volume, tumor lysis syndrome (TLS) is an important identified risk for the treatment with this BCL-2 inhibitor.  
  • Bevacizumab Avastin, Genentech) for patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer in combination with carboplatin and paclitaxel for stage III or IV disease after initial surgical resection. The anti-angiogenesis antibody is currently already in use for the treatment of metastatic colon cancer, lung cancer, glioblastoma, and renal-cell carcinoma.
  • Encorafenib and binimetinib (Braftovi and Mektovi, Array BioPharma) in combination for patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation. Combination therapy with these kinase inhibitors has been approved based on the COLUMBUS trials results.

The FDA extended the approval for Pembrolizumab (Keytruda, Merck) for two additional indications:

  • For patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1). Approval was based on the KEYNOTE-158 conducted in 98 patients. PD-L1 IHC 22C3 pharmDx (Dako North America Inc.) is concurrently approved as a companion diagnostic.
  • For the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL) who have relapsed after two or more prior lines of therapy. Approval was based on KEYNOTE-170.

Guidelines

Guidance from EMA to prepare pharma for Brexit

The European Medicines Agency and the European Commission have updated their guidance to prepare pharmaceutical companies for the UK’s withdrawal from the European Union known as Brexit. UK will become a third country as of 30 March 2019 based on that the Brexit is scheduled for the end of May 2019. Guidance aims to support companies for undisrupted supply of their medicines in the EU. The updates are marked as “new” in the European Commission/EMA questions and answers and include information on how the status of inspection outcomes by MHRA and batch release processes for medicines will be affected. The document also explains the effects of Brexit on the scientific opinions of the Committee for Medicinal Products for Human Use (CHMP) for ancillary medicinal substances in medical devices requested by UK notified bodies. EMA practical guidance is also updated for procedures on the changes in marketing authorization to allow the companies for continued marketing of their medicines in the EU after Brexit. Companies are encouraged to check EMA page regularly for Brexit related guidance as more guidance documents are under preparation.

Draft guidance from FDA on oncology therapeutic radiopharmaceuticals

Oncology therapeutic radiopharmaceuticals: nonclinical studies and labeling recommendations guidance for industry is specific and provides additional information for therapeutic radiopharmaceuticals in oncology indications covering the topics on nonclinical studies in support of first-in-human (FIH) trials and approval for oncology therapeutic radiopharmaceuticals. This complementary guidance supplements the information for industry Nonclinical Evaluation of Late  Radiation Toxicity of Therapeutic Radiopharmaceuticals for the design of late radiation toxicitystudies. The following concepts are discussed: 1-) Evaluation of toxicities from the ligand, 2-) Evaluation of radiation toxicities 3-) Information for product labeling as related to reproductive toxicity, genotoxicity, 48 carcinogenicity, contraception, and use in lactating women. It is important to note that updated information is not applicable to oncology therapeutic radiopharmaceuticals with a local route of administration, (such as intratumoral, intrathecal, or inhalation route of administration) as the nonclinical study designs and the approach to FIH dose selection may not apply.