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NEWS AND PUBLICATIONS

Pembrolizumab in microsatellite-instability-high advanced colorectal cancer

While programmed death 1 (PD-1) blockade in microsatellite-instability-high (MSI-H) or mismatch-repair-deficient (dMMR) tumors after previous therapy has clinical benefit, its efficacy as first-line therapy for MSI-H/dMMR advanced/metastatic colorectal cancer remains unknown. In the Phase 3 open-label KEYNOTE-177 trial, treatment-naïve patients with MSI-H/dMMR advanced/metastatic colorectal cancer received pembrolizumab or chemotherapy every 2 weeks. At the second interim analysis (median follow-up: 32.4 months), pembrolizumab was superior to chemotherapy regarding progression-free survival (PFS; median: 16.5 vs 8.2 months; p=0.0002). The estimated restricted 2-year mean survival was 13.7 vs 10.7 months. The overall response rates were 43.8% and 33.1% in the pembrolizumab vs chemotherapy groups. Noteworthy, among patients with an overall response, 83% in the pembrolizumab group, as compared with 35% of patients in the chemotherapy group, had ongoing responses at 24 months. These results, published in the New England Journal of Medicine, highlight the efficacy of pembrolizumab in treatment-naïve patients with MSI-H/dMMR advanced/metastatic colorectal cancer.

INDUSTRY

  • Bayer and Atara Biotherapies enter strategic collaboration for mesothelin-targeted chimeric antigen receptor (CAR) T-cell therapies for solid tumors. Atara will receive upfront payment of $60 million, and up to a total of $610 million for development, regulatory and commercialization milestones, plus tiered royalties up to low double-digit percentage of net sales.
  • Relay Therapeutics and Genentech enter worldwide collaboration and licensing agreement for RLY-1971, a potent Src homology-2 domain containing protein tyrosine phosphatase-2 inhibitor. Under the terms of the agreement, Relay will receive $75 million upfront and is eligible to receive an additional $25 million in near-term payments and $695 million in additional potential milestones, plus royal global net product sales. Genentech will assume development of RLY-1971 with the potential to expand into multiple combination studies.
  • Hummingbird Biosciences and Tempus enter collaboration to harness AI-driven precision medicine to accelerate clinical development of HMBD-001 in HER3-driven cancers, including those that harbor neuregulin 1 fusions.

EMA

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

New medicines:

  • Trastuzumab deruxtecan (Enhertu, Daiichi Sankyo Europe), for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received two or more prior anti HER2 based regimens.
  • Fedratinib (Inrebic, Celgene Europe), for the treatment of disease-related splenomegaly or symptoms in adult patients with primary myelofibrosis, post polycythemia vera myelofibrosis or post essential thrombocythemia myelofibrosis who are JAK inhibitor naïve or who have been treated with ruxolitinib.
  • Moxetumomab pasudotox (Lumoxiti, AstraZeneca), as monotherapy is indicated for the treatment of adult patients with relapsed or refractory hairy cell leukemia after receiving at least two prior systemic therapies, including treatment with a purine nucleoside analogue.
  • Selpercatinib (Retsevmo, Eli Lilly), for the treatment of advanced RET fusion-positive non-small cell lung cancer (NSCLC) who require systemic therapy following prior treatment with immunotherapy and/or platinum-based chemotherapy and advanced RET fusion-positive thyroid cancer who require systemic therapy following prior treatment with sorafenib and/or lenvatinib.
  • Tucatinib (Tukysa, Seagen), in combination with trastuzumab and capecitabine, for the treatment of adult patients with HER2-positive locally advanced or metastatic breast cancer who have received at least 2 prior anti-HER2 treatment regimens.

Generics/Biosimilars:

  • Lenalidomide (Lenalidomide Krka d.d. Novo mesto), for multiple myeloma, myelodysplastic syndromes, mantle cell lymphoma and follicular lymphoma.
  • Sunitinib Accord (Accord Healthcare), for the treatment of unresectable and/or metastatic malignant gastrointestinal stromal tumor in adults after failure of imatinib treatment due to resistance or intolerance; for the treatment of advanced/metastatic renal cell carcinoma in adults; for the treatment of unresectable or metastatic, well-differentiated pancreatic neuroendocrine tumors with disease progression in adults.

Extensions of Indications:

  • Avelumab (Bavencio, Merck Europe), as monotherapy for the first-line maintenance treatment of adult patients with locally advanced or metastatic urothelial carcinoma who are progression-free following platinum-based chemotherapy.
  • Pembrolizumab (Keytruda, Merck), as monotherapy is indicated for the first‑line treatment of metastatic MSI‑H or dMMR colorectal cancer in adults.

FDA

The FDA granted approval for:

  • Ponatinib (Inclusig, TakedaPharma) as a supplemental new drug to treat patients with chronic-phase chronic myeloid leukemia (CML) with resistance or intolerance to at least two prior kinase inhibitors. Approval was based on the Phase 2 PACE trial, which reported that 55% of patients achieved major cytogenetic response by 12 months. 
  • Selinexor (Xpovio, Jaryopharm Therapeutics) in combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. Median progression-free survival (PFS), assessed in the Phase 3 BOSTON trial, was 13.9 vs 9.5 months in the selinexor combination therapy vs bortezomib and dexamethasone arms.
  • Relugolix (Orgovyx, Myovant Sciences) adult patients with advanced prostate cancer, based on the results of the Phase 3 HERO trial, which reported a medical castration rate of 96.7% in the relugolix arm.
  • Osimertinib (Tagrisso, AstraZeneca) for adjuvant therapy after tumor resection in patients with non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test. Approval was based on the Phase 3 ADAURA trial, in which the disease-free survival (DFS) was not reached in osimertinib-treated patients; DFS was 19.6 months in the placebo arm.
  • Margetuzumab-cmkb (Margenza, MacroGenics) in combination with chemotherapy for the treatment of an advanced type of breast cancer in patients who failed two or more prior therapies. Approval was based on the Phase 3 SOPHIA trial, which reported a median PFS of 5.8 vs 4.9 months in the margetuximab vs control arms.
  • Pralsetinib (Gavreto, Blueprint Medicines Corporation) or adult and pediatric patients 12 years of age and older with advanced or metastatic RET-mutant medullary thyroid cancer who require systemic therapy or RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate). Approval was based on the Phase 1-2 ARROW trial, which reported an overall response rate (ORR) of 60%, with 79% of responders having responses lasting ≥6 months.
  • Gallium 68 PSMA-11 (Siemens Healthineers), the first drug for positron emission tomography (PET) imaging of prostate-specific membrane antigen (PSMA) positive lesions in men with prostate cancer. Ga 68 PSMA-11 is indicated for patients with suspected prostate cancer metastasis potentially curable by surgery/radiation therapy and for patients with suspected prostate cancer recurrence based on elevated serum prostate-specific antigen levels. Ga 68 PSMA-11 is a radioactive diagnostic agent administered in the form of an intravenous injection.

The FDA also granted breakthrough therapy designation to the following compound to help boost its development:

Pegloprastide (AVB-620, Avelas), for the intraoperative detection and visualization of positive margins during breast cancer surgery. Pegloprastide is designed to deliver a fluorescent marker to cancer cells to aid surgeons in identifying positive margins in real time during surgery.

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