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

NEWS AND PUBLICATIONS

Breast cancer risk genes association analysis – clinical utility for prediction panels
Despite the wide use of genetic testing for breast cancer susceptibility, evidence of genetic association with breast cancer is weak for many genes and reliable subtype-specific risk estimates are lacking. The Breast Cancer Association Consortium (BCAC) aimed to shed light on this by sequencing samples from >113,000 women (60,466 with breast cancer and 53,461 controls). Subsequently, in large analyses for protein-truncating and rare missense variants, BCAC estimated odds ratios for breast cancer overall and specific subtypes. Protein-truncating variants in the following genes were associated with a risk of breast cancer overall: ATM, BRCA1, BRCA2, CHEK2, and PALB2 (p<0.0001) and BARD1, RAD51C, RAD51D, and TP53 (p<0.05). For protein-truncating variants in 19 of the remaining 25 evaluated genes, the upper limit of the 95% confidence interval of the odds ratio for breast cancer overall was less than 2.0.

Odds ratios were higher for estrogen receptor (ER)–positive than for ER-negative disease for protein-truncating variants in ATM and CHEK2, and lower for protein-truncating variants in BARD1, BRCA1, BRCA2, PALB2, RAD51C, and RAD51D. Rare missense variants in ATM, CHEK2, and TP53 and missense variants in BRCA1, BRCA2, and TP53 were associated with a risk of breast cancer overall (p<0.001).

cato sms graph

These results, published in the New England Journal of Medicine, define the most clinically useful genes for inclusion on breast cancer risk prediction panels, thus providing invaluable genetic counseling.

INDUSTRY

  • Parexel and NeoGenomics enter strategic collaboration in precision medicine to improve trial designs and accelerate patient matching in oncology clinical trials by applying real-world genomics data to accelerate patient matching and optimize trial design, site selection, clinical development and translational research. Financial agreements have not been disclosed.

EMA

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

New medicines:

  • Dostarlimab (Jemperli, GSK) as monotherapy for the treatment of adult patients with recurrent or advanced mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) endometrial cancer (EC) that has progressed on or following prior treatment with a platinum containing regimen.

Generics/Biosimilars:

Extensions of indications:

  • Cabozantinib (Cabometyx, Ipsen Pharma), which is now recommended in combination with nivolumab, for the first-line treatment of advanced renal cell carcinoma in adults.
  • Nivolumab (Opdivo, BMS), which is now recommended in combination with cabozantinib for the first-line treatment of adult patients with advanced renal cell carcinoma.
  • Isatuximab (Sarclisa, Sanofi Aventis Europe) in combination with carfilzomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy.

FDA

The FDA granted approval for:

  • Trilaciclib (Cosela, G1 Therapeutics), the only FDA-approved therapy that helps proactively deliver multilineage myeloprotection to patients with extensive-stage small cell lung cancer being treated with chemotherapy. G1 Therapeutics received Breakthrough Therapy Designation from the FDA in 2019 based on positive data in SCLC patients from three randomized Phase II clinical trials. The company will continue by conducting post-marketing activities, including in vitro drug-drug interaction and metabolism studies.
  • Melphalan flufenamide (Pepaxto, Oncopeptides AB) in combination with dexamethasone for adult patients with relapsed/refractory multiple myeloma who have received at least four prior lines of therapy and whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent, and one CD-38 directed monoclonal antibody. Approval was based on the HORIZON Phase 2 trial, which reported an overall response rate (ORR) of 23.7% and a median duration of response of 4.2 months following melphalan treatment.
  • Cemiplimab-rwlc (Libtayo, Regeneron Pharmaceuticals) for the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression (Tumor Proportion Score [TPS] > 50%) as determined by an FDA-approved test, with no EGFR, ALK or ROS1 aberrations. Approval was based on the Phase III Study 1624, which reported statistically significant improvements in overall survival (OS) and progression-free survival (PFS) for patients receiving cemiplimab-rwlc compared to those treated with platinum-based chemotherapy.
  • Cemiplimab-rwlc (Libtayo, Regeneron Pharmaceuticals) for locally advanced and metastatic basal cell carcinoma. Approval was based on the Phase II Study 1620, which reported an ORR of 29% in patients receiving cemiplimab, with a median duration of response not reached and 79% of responders maintaining their response for at least 6 months.
  • Lisocabtagene maraleucel (Breynazi, Juno Therapeutics) for the treatment of adult patients with relapsed or refractory (R/R) large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B. Approval was based on the single-arm open label TRANSCEND Phase I trial, which reported an ORR of 73% and a complete response (CR) rate of 54%.
  • Umbralisib (Ukoniq,TG Therapeutics) a kinase inhibitor including PI3K-delta and casein kinase CK1-epsilon receiving accelerated approval for the following indications: adult patients with relapsed/refractory marginal zone lymphoma (MZL) who have received at least one prior anti-CD20-based regimen; adult patients with relapsed/refractory follicular lymphoma (FL) who have received at least three prior lines of systemic therapy. Approval was based on two single-arm cohorts of the UTX-TGR-205 Phase II/III trial, which reported ORRs of 49% in patients with MZL and of 43% in patients with FL.
  • Tepotinib (Tepmetko, EMD Serono), which received accelerated approval for adult patients with metastatic NSCLC harboring mesenchymal-epithelial transition (MET) exon 14 skipping alterations. Approval was based on the VISION Phase II trial, which reported an ORR of 43% among treatment-naïve as well as previously treated patients.

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

  • Asciminib (ABL001, Novartis), an investigational treatment specifically targeting the ABL myristoyl pocket (STAMP), for the treatment of adult patients with Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP), previously treated with two or more tyrosine kinase inhibitors (TKIs).

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