publication date: Jun. 26, 2020

Drugs & Targets

FDA approves Keytruda for cutaneous squamous cell carcinoma

Keytruda was approved by FDA for patients with recurrent or metastatic cutaneous squamous cell carcinoma that is not curable by surgery or radiation.

Keytruda is sponsored by Merck.

Efficacy was investigated in KEYNOTE-629 (NCT03284424), a multicenter, multi-cohort, non-randomized, open-label trial. The trial excluded patients who had previously received therapy with an anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody and those with autoimmune disease or a medical condition that required immunosuppression. Patients received pembrolizumab 200 mg intravenously every 3 weeks until disease progression, unacceptable toxicity, or a maximum of 24 months. Assessment of tumor status was performed every 6 weeks during the first year and every 9 weeks during the second year.

The major efficacy outcome measures were objective response rate and response duration as assessed by blinded independent central review according to RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The ORR was 34% (95% CI: 24, 44) and median response duration was not reached (range: 2.7, 13.1+ months)


Selinexor receives FDA approval for relapsed/refractory diffuse large B-cell lymphoma

Selinexor (Xpovio) was granted accelerated approval from FDA for adult patients with relapsed or refractory diffuse large B-cell lymphoma, not otherwise specified, including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy.

Xpovio is sponsored by Karyopharm Therapeutics.

Approval was based on SADAL (KCP-330-009; NCT02227251), a multicenter, single-arm, open-label trial in patients with DLBCL after two to five systemic regimens. Patients received selinexor 60 mg orally on days one and three of each week.

Efficacy was based on overall response rate and response duration, as assessed by an independent review committee using Lugano 2014 criteria. In 134 patients, the ORR was 29% (95% CI: 22, 38), with complete response in 13%. Of the 39 patients who achieved a partial or complete response, 38% had response durations of at least 6 months and 15% had response durations of at least 12 months.


Oral relugolix NDA accepted for Priority Review by FDA

Myovant Sciences’ New Drug Application for once-daily, oral relugolix (120 mg) for the treatment of men with advanced prostate cancer has been accepted for Priority Review by FDA.

“As recently published in the New England Journal of Medicine, relugolix demonstrated superior efficacy and a 54% lower risk of major adverse cardiovascular events compared to the current standard of care, leuprolide acetate injections, in the Phase 3 HERO study,” Lynn Seely, chief executive officer of Myovant Sciences, said in a statement.

FDA has set a target action date of December 20, 2020 under the Prescription Drug User Fee Act. In its acceptance letter, the FDA also stated that it is currently not planning to hold an advisory committee meeting for this application. If approved, relugolix would be the first and only oral gonadotropin-releasing hormone receptor antagonist treatment for men with advanced prostate cancer.


Keytruda approved in China for second-line treatment of locally advanced or metastatic ESCC indication

Keytruda was approved by the National Medical Products Administration in China as monotherapy for the treatment of patients with locally advanced or metastatic esophageal squamous cell carcinoma whose tumors express PD-L1 (Combined Positive Score [CPS] ≥10) as determined by a fully validated test, following failure of one prior line of systemic therapy.

This new indication was granted full approval based on the overall survival findings from the global phase 3 KEYNOTE-181 trial, including data from an extension of the global study in Chinese patients. With this new approval,

Keytruda is sponsored by Merck.

Keytruda is now approved for five indications across three cancer types in China, including as a first-line treatment for appropriate patients with advanced non-small cell lung cancer (monotherapy and in combination with chemotherapy) and as a second-line treatment for advanced melanoma. The FDA approval in July 2019 was based upon the global KEYNOTE-181 trial.

“In China, more than 90% of esophageal cancers are squamous cell carcinomas, and patients with advanced types of this disease face a poor prognosis and have few treatment options,” Shen Lin, vice president of Clinical Oncology at Beijing Cancer Hospital and Peking University and deputy director of Beijing Institute for Cancer Research, said in a statement.

In the KEYNOTE-181 trial, an improvement in OS was observed in patients who were treated with Keytruda monotherapy compared with chemotherapy in previously treated patients with recurrent or metastatic ESCC whose tumors expressed PD-L1 (CPS ≥10) (HR=0.64 [95% CI, 0.46-0.90]). The median OS was 10.3 months for Keytruda compared with 6.7 months for chemotherapy.

In the extension of the KEYNOTE-181 study in Chinese patients, consistent with the KEYNOTE-181 global study, there was an improvement in OS for patients who were treated with Keytruda monotherapy compared with chemotherapy in previously treated patients with recurrent or metastatic ESCC whose tumors expressed PD-L1 (CPS ≥10) (HR=0.38 [95% CI, 0.19-0.77]). The median OS was 12.0 months for KEYTRUDA compared with 5.4 months for chemotherapy.

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