News & Publications

Novel approach for identifying personalized therapy for relapsed/refractory AML

Ex vivo drug sensitivity/resistance profiling (DSRP) and targeted next-generation sequencing (tNGS) helped define the functional genomic landscape of acute myeloid leukemia (AML) and premises for personalized medicine. Collington et al evaluated the feasibility of a chemogenomic tailored treatment strategy (TTS) guided by parallel DSRP and tNGS for patients with relapsed/refractory AML. On average, 3-4 potentially active drugs were selected per patient, and only five patient samples were resistant to the entire drug panel. Seventeen patients received a TTS-guided treatment, four (23.5%) of which had complete remission, one (5.9%) had partial remission, and five (29.4%) had decreased peripheral blast counts. These data, published in Nature, highlight the utility of novel chemogenomic approaches to determine TTS.

Immune landscapes predict treatment resistance or response in AML

Predicting treatment resistance/response in AML patients is currently a difficult endeavor. To shed light on this, Vadakekolathu et al studied gene expression profiles in bone marrow biopsies and clinical outcomes in three independent cohorts of children and adults with AML. Variable T cell infiltration and interferon (IFN)-driven signatures that could be associated with chemotherapy resistance were observed. Matched samples from patients before/after treatment with the bispecific antibody flotetuzumab indicated that an IFN-γ signature identifies patients likely to respond. These data, published in Science, not only lead to an enhanced understanding of the immune environment of AML, but also help inform future treatment decisions.

Industry

  • Ideaya and GSK announce broad partnership to explore new synthetic lethality programs (MAT2A, Pol Theta, and Werner Helicase) in precision medicine oncology. Under the terms of the agreement, Ideaya will receive: $100 million upfront cash payment, a $20 million equity purchase of common stock in a direct private placement, and a potential $50 million cash option fee for the MAT2A program; 50% United States profit share for te MAT2A and Werner Helicase programs. Ideaya will be responsible for 20% of global development costs for products developed with GSK.
  • AbbVie and Genmab enter broad oncology collaboration to develop and commercialize three of Genamb’s next-generation bispecific antibodies, including epcoritamab. AbbVie will pay Genmab $750 million upfront, with total potential milestone payments of up to $3.15 billion.
  • Pfizer will invest in small and medium-sized biotech companies focused, amongst others, on oncology drug developments to support the sector’s most promising clinical development programs. The investment is planned to be up to $500 million.
  • Innovent Biologics and Roche enter strategic collaboration focused on the discovery, development and commercialization of cellular therapies and bispecific antibodies for the treatment of hematological and solid cancers. Innovent will pay upfront, development and commercial milestones payments, while Roche will retain the option to license developed products upon initial option exercise payments of $140 million plus additional milestone payments up to $1.96 billion.
  • Alphamab Oncology and Sanofi establish strategic collaboration to advance clinical trials that investigate KN026 in combination with docetaxel in HER2+ breast cancer. Patient enrollement has already started in an initial multicenter, open-label trial. Financial aspects of the agreement remained undisclosed.

DRUG APPROVALS

EMA

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

New medicines:

  • Methylthioninium chloride Cosmo (Cosmo Technologies), as a diagnostic agent to enhance visualization of colorectal lesions in adult patients undergoing screening or surveillance colonoscopy. The main benefit of this hybrid medicine is its ability to improve the detection rate of adenomas.

Biosimilars:

  • Bevacizumab (Aybintio, Samsung Bioepis), a monoclonal antibody directed against vascular endothelial growth factor (VEGF) and a biosimilar of the reference product Avastin, authorized in the European Union in 2005. Approval was given for its use in combination with various chemotherapy regimens/immunotherapy (e.g. erlotinib) for treatment of carcinoma of the colon/rectum, breast cancer, non-small cell lung cancer, renal cell cancer, epithelial ovarian, fallopian tube or primary peritoneal cancer, and carcinoma of the cervix.

FDA

The FDA granted approval for:

  • Selinexor (Xpovio, Karyopharm Therapeutics) for adult patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. Approval was based on the Phase IIb SADAL trial, which reported an overall response rate (ORR) of 29% and a complete response (CR) rate of 13% in this hard-to-treat patient population.
  • Tazemetostat (Tazverik, Epizyme) for adult patients with R/R follicular lymphoma (FL) whose tumors are positive for an EZH2 mutation as detected by the FDA-approved EZH2 Mutation Test and who have received at least 2 prior systemic therapies, and for adult patients with R/R FL who have no satisfactory alternative treatment options. Approval was based on the Phase I/II E7438-G000-101 trial, which reported an ORR of 69% in the analyzed patient population, with 12% CR and 57% partial response rates.
  • Pembrolizumab (Keytruda, Merck) for treatment of recurrent/metastatic cutaneous squamous cell carcinoma (cSCC) that is not curable by surgery or radiation and for treatment of adult and pediatric patients with unresectable/metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase] solid tumors, as determined by the FDA-approved test FoundationOneCDx (Foundation Medicine), who have progressed following prior treatment and have no satisfactory alternative treatment options.
  • Gemtuzumab ozogamicin (Mylotargtm, Wyeth Pharmaceuticals) for newly-diagnosed CD33-positive acute myeloid leukemia (AML) to include pediatric patients 1 month and older. Approval was based on the Phase III AAML0531 trial, which reported an event-free survival (EVS; no induction failure, relapse, or death) of 48% vs 40% at 5 years in the ozogamicin combined with chemotherapy arm vs chemotherapy alone. 
  • Lurbinectedin (Zepzelca, Jazz Pharmaceuticals and PharmaMar) for treatment of adult patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy. Accelerated approval was based on the Phase II PM1183 trial, which reported an overall response rate (ORR) of 35.2% in a mixed population of platinum-sensitive and platinum-resistant patients.
  • Nivolumab (Opdivo, Bristol Myers Squibb) for treatment of patients with advanced esophageal squamous cell carcinoma after prior fluoropyrimidine and platinum-based chemotherapy. Approval was based on the Phase III ATTRACTION-3 trial, which reported a median overall survival (OS) of 10.9 vs 8.4 months in patients receiving nivolumab vs investigator’s choice of taxane chemotherapy.

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