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

NEWS AND PUBLICATIONS

Immunovirotherapy for pediatric high-grade gliomas
Recurrent/progressive high-grade gliomas in children and adolescents have historically poor survival (median overall survival [OS] of 5.6 months), partially due to their immunologically silent or “cold” profile, with low numbers of tumor-infiltrating lymphocytes. In a Phase 1 trial, Friedman et al evaluated safety and preliminary efficacy of G207, an oncolytic virotherapy with genetically engineered herpes simplex virus-1 (HSV-1) G207, lacking normal brain tissue replication genes. No dose-limiting toxic effects or serious adverse events were attributed to G207 and the median OS of treated patients was 12.2 months, with G207 markedly increasing the number of tumor-infiltrating lymphocytes. The results, published in The New England Journal of Medicine, possibly herald a new treatment modality for recurrent/progressive pediatric high-grade gliomas. 

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New combination therapies for renal cell carcinoma
With the advent of new-generation targeted therapies, their efficacy in combination regimens with chemotherapy or monoclonal antibodies may change the treatment paradigm of various solid tumors. In the CLEAR Phase 3 trial, Motzer et al evaluated efficacy and safety of lenvatinib plus pembrolizumab (LP), lenvatinib plus everolimus (LE) or sunitinib alone in advanced RCC patients. Results showed a significantly longer median progression-free survival (PFS) in patients treated with LP or LE vs sunitinib (23.9 vs 9.2 months and, respectively, 14.7 vs 9.2 months, p<0.001). The same was observed for overall survival (OS) after LP vs sunitinib treatment (hazard ratio for death 0.66, p<0.005), with LP having an acceptable safety profile. These results, published in The New England Journal of Medicine, highlight the efficacy of combined targeted therapy and monoclonal antibodies in solid tumors such as RCC.

INDUSTRY

  • Artios Pharma and Novartis enter global collaboration to discover and validate next generation DNA damage response (DDR) targets to enhance Novartis’ radioligand therapies (RLT). Under the 3-year deal, Artios and Novartis will perform target discovery and validation, and Novartis will select up to three exclusive DDR targets, receiving worldwide rights to use them with its RLTs. Financially, Novartis will make an upfront payment of $20 million and provide research funding, while Artios will receive up to $1.3 billion in discovery, development, regulatory and sales-based milestones, in addition to royalty payments on net sales of products making it to market.

EMA

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

New medicines:

  • Selumetinib (Koselugo, AstraZeneca) for the treatment of pediatric patients with neurofibromatosis type 1 (NF1) plexiform neurofibromas (PN).
  • Azacitidine (Onureg, BMS Pharma) for the maintenance treatment of patients with acute myeloid leukemia.

New generic medicines:

  • Abiraterone acetate (Abiraterone Krka, Krka Novo mesto) for the treatment of metastatic prostate cancer.

Extensions of indications:

  • Nivolumab (Opdivo, BMS Pharma) in combination with ipilimumab is indicated for the first line treatment of adult patients with unresectable malignant pleural mesothelioma.
  • Osimertinib (Tagrisso, AstraZeneca) as monotherapy for the adjuvant treatment after complete tumor resection in adult patients with stage IB-IIIA non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations.
  • Venetoclax (Venclyxto, AbbVie Deutschland) in combination with a hypomethylating agent is indicated for the treatment of adult patients with newly diagnosed acute myeloid leukemia who are ineligible for intensive chemotherapy.
  • Ipilimumab (Yervoy, BMS Pharma) in combination with nivolumab is indicated for the first‑line treatment of adult patients with unresectable malignant pleural mesothelioma.

FDA

The FDA granted approval for:

  • Loncastuximab tesirine-lpyl (Zynlonta, ADC Therapeutics) a CD19-directed antibody and alkylating agent conjugate, for adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from low grade lymphoma, and high-grade B-cell lymphoma. The accelerated approval was given based on the LOTIS-2 Phase 2 trial, which reported an overall response rate (ORR) of 48.3% with a complete response (CR) rate of 24.1% in patients treated with this compound. 
  • Dostarlimab-gxly (Jemperli, GSK) for adult patients with mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer, as determined by an FDA-approved test, that has progressed on or following a prior platinum-containing regimen. The accelerated approval was given based on the GARNET Phase 1 trial, which reported a confirmed ORR of 42.3% and a CR rate of 12.7% in patients treated with this compound.
  • Nivolumab (Opdivo, BMS) in combination with fluoropyrimidine- and platinum-containing chemotherapy, as the first immune-oncology treatment for advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma. The approval was based on the CHECKMATE-649 Phase 3 trial, which reported a statistically significant improvement in both PFS and OS for patients with a programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥5 receiving nivolumab and chemotherapy vs chemotherapy alone (median PFS was 7.7 vs 6.0 months and median OS was 14.4 vs 11.1 months, respectively). 
  • Sacituzumab govitecan (Trodlevy, Immunomedics) for patients with locally advanced or metastatic urothelial cancer (mUC) who previously received a platinum-containing chemotherapy and either a programmed death receptor-1 (PD-1) or a PD-L1 inhibitor. This accelerated approval was granted based on the TROPHY Phase 2 trial, which reported a confirmed ORR of 27.7%, with 5.4% complete responses and 22.3% partial responses.
  • New dosing regimen for cetuximab (Erbitux, ImClone) of 500 mg/m2 as a 120-minute intravenous infusion every two weeks (Q2W) for patients with K-RAS wild-type, endothelial growth factor receptor (EGFR)-expressing colorectal cancer (mCRC) or squamous cell carcinoma of the head and neck (SCCHN). The approval was based on population pharmacokinetic (PK) modeling analyses comparing predicted 500 mg Q2W to observed cetuximab exposures in patients who received cetuximab 250 mg weekly.  
  • Sacituzumab govitecan (Trodelvy, Immunomedics) for patients with unresectable locally advanced/metastatic triple-negative breast cancer (mTNBC) who have received ≥2 prior systemic therapies, of which ≥1 for metastatic disease. This regular approval followed the accelerated approval granted in 2020 based on the results of the ASCENT Phase 3 trial, which reported a median PFS of 4.8 vs 1.7 months in patients treated with sacituzumab govitecan vs chemotherapy.

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

  • Bemarituzumab (Amgen), as first-line treatment for patients with fibroblast growth factor receptor 2b (FGFR2b) overexpressing and human epidermal growth factor receptor 2 (HER2)-negative metastatic and locally advanced gastric and gastroesophageal (GEJ) adenocarcinoma in combination with modified FOLFOX6 (fluoropyrimidine, leucovorin, and oxaliplatin), based on an FDA-approved companion diagnostic assay showing at least 10% of tumor cells overexpressing FGFR2b. 

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