Home Health Care ASCO 2021 recap: Lynparza’s lift, Grail goes on, LAG validation & more

ASCO 2021 recap: Lynparza’s lift, Grail goes on, LAG validation & more

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The annual meeting of the America Society of Clinical Oncology came and went, and for the second year in a row, the pandemic meant that the cancer gathering was an all-digital affair.

Big pharmaceutical companies grabbed most of the headlines with data supporting further development of some clinical candidates and in at least one case, potential expanded use of a blockbuster cancer drug as an earlier treatment. Targeted therapies have been gaining steam and this year’s conference saw the unveiling of data validating some new targets. Here’s a look back at some of the highlights from ASCO 2021.

Targeted cancer drugs

The past year has seen several targeted cancer therapies win accelerated FDA approval, and ASCO provided a look at the latest data for some of them. Ahead of the conference, Amgen won accelerated FDA approval for sotorasib (Lumakras), the first drug approved to treat cancers driven by a KRAS gene mutation. The approval of the drug in non-small cell lung cancer was based on the 36% objective response rate to the drug in an open-label study that evaluated the therapy in 124 patients. Overall survival data presented at ASCO and published in the New England Journal of Medicine showed that the median overall survival was 12.5 months as of the March 15 cutoff date.

Johnson & Johnson also received an FDA approval ahead of ASCO, a decision for Rybrevant as a treatment for non-small cell lung cancer patients whose tumors have a certain genetic signature—an alteration at the exon 20 region of the EGFR gene. The FDA approval was based on data from an 81-patient open label study in which the overall response rate was 40%. Those results were presented at the cancer conference. The median overall survival in those treated with the J&J drug 22.8 months compared 13.1 months in those treated with real-world therapies.

Meanwhile, Novartis unveiled news for a different type of targeted therapy. The pharmaceutical giant reported Phase 3 data for 177LU-PSMA-617, a radiation therapy that binds to a protein overexpressed on prostate cancer cells. In the 831-patient study, overall survival in the treatment group was 15.3 months compared to 11.3 months for those who received the standard of care. Based on that four-month improvement, Novartis will look ahead to an FDA submission. The company also plans to explore use of 177LU-PSMA-617 in other types of cancer.

Not all of Novartis’s ASCO news was good. The company also reported that a different radioligand, Lutathera, failed the main goal of improving progression free survival in a pivotal study in midgut neuroendocrine tumors. However, the drug did improve overall survival.

Merck, AstraZeneca report PARP progress

Merck and AstraZeneca reported data supporting use of their drug, Lynparza, earlier in the treatment of breast cancer patients whose disease is associated with the BRCA 1 or BRCA 2 mutations. These mutations account for about 5% of all breast cancers. When treated early, surgery, radiotherapy, and chemotherapy can lead to good patient outcomes. But the cancer can recur. To keep it from coming back, physicians use an adjuvant, which is a therapy given after the initial treatment.

Lynparza, a PARP inhibitor, is already approved for metastatic breast cancer. According to the results of a Phase 3 study evaluating the drug as an adjuvant for breast cancer, the risk of cancer recurrence, a second cancer, or patient death, was reduced by 42% compared to a placebo, after one year. The results are preliminary, and patients will continue to be followed. But Andrew Tutt, chair of the steering committee for the clinical trial and a professor of oncology at The Institute of Cancer Research, London, and Kings College London, said that the results show the drug has potential to be used as a follow-on to earlier treatment in patients with BRCA 1 or 2 mutations.

Digging into diagnostics data

Eyes are on Grail because its proposed acquisition by Illumina faces opposition from antitrust authorities. At ASCO the company kept the focus on its cancer diagnostic. The company has said that its Galleri test can detect more than 50 types of cancer from just a small blood sample—early detection that can lead to earlier intervention.

Galleri is being evaluated in 6,629 people age 50 and older. This age group faces a higher risk of cancer, but clinical trial participants did not have active cancer at the start of the study. In preliminary results, Grail reported that an earlier version of its diagnostic accurately detected 29 cancers across 13 types of the disease. Of the new cancers detected, nine of 23 (40%) were localized and more than half of those cancers were detected before they had spread to a more advanced stage. Those participants will be followed for another 12 months. Final study results are expected in the first half of next year.

Stars are aligning for Constellation Pharma

Ahead of the conference, MorphoSys announced a $1.7 billion deal to acquire Constellation Pharmaceuticals. Attention focused on pelabresib, a small molecule that Cambridge, Massachusetts-based Constellation has advanced to late-stage testing in myelofibrosis. But MorphoSys executives say they’re also excited about CPI-0209, an earlier-stage Constellation compound that has potential applications in both solid and liquid tumors. ASCO offered an early look at Phase 1/2 results for the small molecule.

CPI-0209 blocks an enzyme called EZH2. The Phase 1 part of the study produced the safety and tolerability results needed to select the dose for Phase 2 testing. The Phase 1 test also corroborated the target engagement observed in preclinical research and showed early signs the drug is working. Constellation reported one mesothelioma patient showed a durable partial response after four cycles of treatment while in two other patients, the disease became stable—tumors were neither growing nor shrinking.

News for a new cancer target

The gene fusion NRG1 is rare, but when it is found, it’s overexpressed in cancer cells but not in healthy ones, making it a promising cancer drug target. Merus aims to drug cancers characterized by this genetic signature with its bispecific antibody, zenocutuzumab, or “zeno.”

At ASCO, Netherlands-based Merus presented the latest Phase 1/2 data, which showed a 29% overall response rate in 45 patients. Tumor reduction was observed in four types of cancer: pancreatic, breast, cholangiocarcinoma, and non-small cell lung cancer. The results are encouraging but the sample size is small. Responses in multiple types of tumors could lead to a tumor-agnostic indication for the drug, though executives acknowledged that discussions with regulators are needed before determining whether these data are enough to support a drug application.

LAG, but not least

The class of cancer immunotherapies called checkpoint inhibitors block the proteins PD-1 and PDL-1. Bristol Myers Squibb presented Phase 3 results in advanced melanoma for relatlimab, an antibody drug that targets a different checkpoint protein called LAG-3.

The combination of relatlimab and Bristol’s PD-1 inhibitor nivolumab worked better at stopping melanoma from progressing compared to nivolumab alone. Bristol’s Phase 3 results targeting LAG-3 provided validation for others pursuing this target. Merck’s favezelimab is in late-stage testing in colorectal cancer; Phase 1 data were presented at this year’s conference.

In other LAG-3 news, Immutep presented positive Phase 2 data for its drug, eftilagimod alpha. The Sydney, Australia-based drug developer is testing its LAG-3 inhibitor in combination with Merck’s Keytruda as a first-line treatment for patients with non-small cell lung cancer, and as a second-line treatment for head and neck squamous cell carcinoma. So far, nearly 50% of the patients that that could be evaluated have responded to the treatment, Immutep reported.

Public domain image by Stuart S. Martin via the National Cancer Institute

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