Reading our newsletter will keep you up to date with last month’s news items on oncology drug development!

NEWS AND PUBLICATIONS

New advances in the treatment of B-cell malignancies
While Bruton’s tyrosine kinase (BTK) inhibitors are effective in multiple B-cell malignancies, patients continue to discontinue treatment due to resistance and/or intolerance. In this study, published in The Lancet, Mato et al evaluated the safety and efficacy of pirtobritinib, a highly selective reversible BTK inhibitor in the Phase 1/2 BRUIN trial. The compound presented with a positive safety profile in patients with previously treated B-cell malignancies, with adverse events (AEs) occurring in ≥10% of 323 patients being fatigue (20%), diarrhea (17%) and contusion (13%) and the most common ≥Grade 3 AE being neutropenia (10%).

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Grade 3 atrial fibrillation, an AE commonly encountered with this class of compounds, was not observed in patients from this trial. The overall response rate (ORR) was similar in chronic lymphocytic leukemia (CLL) patients with previous covalent BTK inhibitor resistance (67%), covalent BTK inhibitor intolerance (52%), BTK C481-mutant (71%) and BTK wild-type (66%) disease. In patients with mantle cell lymphoma previously treated with BTK inhibitors, the ORR was 52%. Overall, pirtobrutinib was safe and active in multiple B-cell malignancies, including those in patients already treated with BTK inhibitors in the past, thus highlighting that this compound is fit to address a growing unmet need for alternative therapies.

INDUSTRY

  • Amgen buys Five Prime Therapeutics for $1.9 billion in cash in a deal that will add new cancer therapies to Amgen’s pipeline. Amgen will pay $38 a share for Five Prime and the transaction will give Amgen access to Five Prime’s lead drug, bemarituzumab, an experimental treatment for a form of gastric cancer that is moving into final-stage studies.

EMA

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

New medicines:

  • Duvelisib (Copiktra, Verastem Europe GmbH), or the treatment of adult patients with relapsed or refractory chronic lymphocytic leukaemia  (CLL) and refractory follicular lymphoma (FL).

Extensions of indications:

  • Atezolizumab (Tecentriq, Roche) as monotherapy for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have a PD-L1 expression ≥ 50% tumor cells (TC) or ≥ 10% tumor-infiltrating immune cells (IC) and who do not have EGFR mutant or ALK-positive NSCLC.
  • Enzalutamide (Xtandi, Astellas Parma Europe) the treatment of adult men with metastatic hormone-sensitive prostate cancer (mHSPC) in combination with androgen deprivation therapy (ADT).

FDA

The FDA granted approval for:

  • Daunorubicin and cytarabine (Vyexos, Jazz Pharmaceuticals), for use in the additional indication of newly-diagnosed therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC) in pediatric patients aged one year and older. The approval for this new indication is supported by safety data from two single-arm trials: the Phase 1/2 AAML1421 trial and the Phase 1 CPX-MA-1201 trial. Both studies found no differences in the safety profile based on age. 
  • Idecabtagene vicleucel (Abecma, Bristol Myers Squibb) as the first B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cell immunotherapy for the treatment of adult patients with relapsed or refractory multiple myeloma after four or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. Approval was based on the Phase 2 KarNMa pivotal trial, which reported an ORR of 72% and a complete response rate of 28% in patients with relapsed or refractory multiple myeloma who had received at least three prior lines of therapy including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody.
  • Pembrolizumab (Keytruda, Merck Sharp & Dohme Corp.) in combination with platinum and fluoropyrimidine-based chemotherapy for patients with metastatic or locally advanced esophageal or gastroesophageal (GEJ) (tumors with epicenter 1 to 5 centimeters above the gastroesophageal junction) carcinoma who are not candidates for surgical resection or definitive chemoradiation. Approval was based on the Phase 3 KEYNOTE-590 trial, which reported median overall survival (OS) and progression-free survival (PFS) of 12.4 vs 9.8 months and, respectively, 6.3 vs 5.8 months in the combined therapy vs the chemotherapy arms.
  • Tivozanib (Fotivda, AVEO Pharmaceuticals) a kinase inhibitor, for adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies. Approval was based on the Phase 3 TIVO-3 trial, which reported a median progression-free survival (PFS) of 5.6 vs 3.9 months and an ORR of 18% vs 8% in the tivozanib vs sorafenib arms.
  • Lorlatinib (Lorbena, Pfizer) for patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive, detected by the FDA-approved Ventana ALK (D5F3) CDx test (Ventana Medical Systems). Approval was based on the Phase 3 B7461006 trial, which reported an improvement in progression-free survival (PFS) after lorlatinib vs crizotinib treatment.
  • Axicabtagene ciloleucel (Yescarta, Gilead), the first chimeric antigen receptor (CAR) T cell therapy approved for indolent follicular lymphoma. Approval was based on the Phase 2 ZUMA-5 trial, in which 91% of patients with relapsed/refractory follicular lymphoma responded to the drug, including an estimated 74% of patients with continued remission at 18 months.

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

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