2021-06-09| R&DTechnology

Day 3 ASCO 2021 Roundup: Lynparza, Keytruda and Novartis’ Radioligand Therapy Take Honors in Plenary Session

by Rajaneesh K. Gopinath
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The third day of the ASCO 2021 virtual annual meeting featured several exciting clinical studies. Here we briefly summarize the plenary session that showcased some pathbreaking trial results.


AZ, Merck’s Lynparza Registers Practice-Changing Results in Breast Cancer Patients

Lynparza (olaparib) is a PARP inhibitor (PARPi) that is FDA approved for BRCA1/2 associated breast, ovarian, prostate, and pancreatic cancers. In 2018, it bagged the approval for treating germline BRCA-mutated (gBRCAm) metastatic breast cancer based on encouraging Phase 3 results from OlympiAD and EMBRACA trials.

Although lynparza is approved as first-line and maintenance treatments, it is untested as adjuvant therapy in gBRCAm malignancies. In Phase 3, OlympiA trial researchers tested whether a 1-year treatment of Olaparib yielded any benefit in patients with gBRCAm containing HER2 negative early breast cancer after they have undergone surgery and chemotherapy.

Preliminary analysis showed that olaparib met the primary endpoint of 3y invasive disease free survival (IDFS) and the secondary endpoint of distant disease-free survival (DDFS). In other words, the drug significantly reduced the risk of relapse or death by 42% as compared to placebo, with a safety profile consistent with previous studies. The study results are published in The New England Journal of Medicine.


Combination of PD-1 Inhibitor with Treatment Standard Benefits Nasopharyngeal Carcinoma Patients

Nasopharyngeal carcinoma (NPC) is a rare tumor that is usually diagnosed at an advanced stage. The current standard of care (SOC) involves the combination of gemcitabine/cisplatin chemotherapy. However, in the case of PD-L1 positive tumors, a combination of checkpoint inhibitors like Merck’s Keytruda or BMS’ Opdivo is recommended together with the SOC. In a recent Phase 3 trial, researchers evaluated the combination of Junshi Biosciences’ IgG4K anti–PD-1 monoclonal antibody, toripalimab, with the treatment standard.

The JUPITER-02 trial randomized 289 patients to either receive toripalimab (n=146) or placebo (n=143). Results showed that the drug arm yielded a significant improvement in Progression free survival (PFS) with a median PFS of 11.7 months versus the placebo’s 8.0. Toripalimab also registered superior benefits in overall response rate (77.4% vs. 66.4%) and median duration of response (10.0 vs. 5.7 months).

Toripalimab is the first anti-PD-1 antibody from China to receive the FDA’s Breakthrough Therapy designation (BTD). The drug is currently approved in China for various indications, including metastatic NPC. Besides the BTD in this indication, the drug has bagged the FDA’s Fast Track and Orphan Drug status for other cancer types.

“This is one of the first studies in metastatic or recurrent nasopharyngeal carcinoma to show a benefit of a combination of a PD-1 inhibitor with chemotherapy,” said Dr. Julie R. Gralow, CMO and Executive VP of ASCO, in a media briefing. “With FDA approval, these findings should prove to be practice-changing,” Dr. Gralow added.


Impressive Phase 3 Results Puts Novartis’ Radioligand Therapy as a Promising Prostate Cancer Treatment

Prostate cancer is the second most common cancer in men worldwide. When diagnosed, patients typically undergo radical prostatectomy or radiological therapy, followed by androgen deprivation therapy (ADT). When cancer advances to a stage where it no longer completely responds to androgen deprivation, it is called castration-resistant prostate cancer (CRPC).

Patients with metastatic castration-resistant prostate cancer (mCRPC) are fortunate to have about ten FDA-approved therapy options besides ADT. However, the duration of response of those treatments is often short, partly due to the emergence of resistant and progressive cancer.

Patients with mCRPC lesions highly express the prostate-specific membrane antigen (PSMA). Novartis’ targeted radioligand therapy, 177Lu-PSMA-617, delivers ß-particle radiation to PSMA-expressing cells and surrounding microenvironment to cause DNA damage and block further duplication of cancer cells.

In the Phase 3 VISION trial, 831 patients with PSMA-positive mCRPC were randomized to receive either six infusions of 177Lu-PSMA-617 (7.4 GBq every 6 weeks x 6 cycles) in combination with the investigator-chosen best standard of care (SOC) or SOC alone.

Results showed that 177Lu-PSMA-617 in combination with SOC significantly improved radiographic progression-free survival (rPFS) as compared to SOC alone (8.7 vs. 3.4 months). The OS was also significantly improved (15.3 vs. 11.3 months). In conclusion, the radioligand therapy plus SOC treatment is a well-tolerated regimen that met its primary and secondary endpoints.

In the accompanying discussion session, Dr. Mary-Ellen Taplin of the Dana Farber Cancer Institute said that if 177Lu-PSMA-617 is FDA-approved, it will add to the palliative systemic treatment options for mCRPC. She is optimistic that future radiopharmaceuticals approaches will be even more impactful.


Keytruda Excels as Adjuvant Therapy in Renal Cell Carcinoma Trial

Renal cell carcinoma (RCC) is the most common type of kidney cancer, which is twice as common in men as in women. Cancer relapse post-surgery is a significant problem with high-risk clear cell RCC (ccRCC), necessitating an effective perioperative therapy for patients.

The treatment landscape for advanced or metastatic RCC has rapidly transformed over the past decades. It started with the cytokine era, followed by the targeted therapy era, and more recently, the checkpoint inhibitor era beginning with the approval of Opdivo in 2015 and later the introduction of IO combination therapy.

Given the success of checkpoint inhibitors in several metastatic cancers, several studies are underway testing them as adjuvant therapy. Currently, the only indication for which a checkpoint inhibitor is FDA-approved as adjuvant treatment is Merck’s Keytruda (pembrolizumab) for melanoma.

In Phase 3, KEYNOTE-564 trial, Keytruda was evaluated as adjuvant therapy for patients with RCC. Results showed that the drug met the primary endpoint of disease-free survival (DFS). Keytruda demonstrated a statistically significant and clinically meaningful improvement with a DFS rate of 77.3% in 24 months (compared to placebos’ 68.1%).

Although additional follow-up is necessary to evaluate whether the drug can achieve the secondary endpoint of overall survival (OS), the estimated preliminary OS rate was 96.6% for Keytruda versus 93.5% for placebo. KEYNOTE-564 is the first positive Phase 3 study with a checkpoint inhibitor in adjuvant RCC. These results support Keytruda as a potential new standard of care for patients with RCC in the adjuvant setting.

Related Article: Day 2 ASCO 2021 Roundup: Focus on Equity in Cancer Care, Highlights from Breast Cancer and Gastrointestinal Cancer Studies

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