Gina Mauro

Teclistamab (formally JNJ-64007957) demonstrated encouraging clinical activity, along with a tolerable safety profile, in patients with relapsed/refractory multiple myeloma, according to results from an ongoing phase 1 study (NCT03145181).1 Results showed that at the recommended phase 2 dose (RP2D), the objective response rate (ORR) with teclistamab was 73% and the very good partial response rate (VGPR) or better was 55%; the complete response (CR) rate or better was 23%.

The agent was also found to be well tolerated at the RP2D, which was 1500 μg/kg given subcutaneously (SC); the maximum-tolerated dose (MTD) was not identified, and all reports of cytokine release syndrome (CRS) were of grades 1/2 and were generally confined to step-up doses and the first full doses of treatment.

“Teclistamab is an off-the-shelf therapy targeting BCMA, [and it] showed promising efficacy in heavily pretreated patients with relapsed/refractory multiple myeloma,” said lead study author Alfred L. Garfall, MD, an assistant professor of medicine at the Hospital of the University of Pennsylvania, in a virtual presentation of the data.

There continues to be an unmet need for patients with relapsed/refractory multiple myeloma, he explained; for those who progress on available therapies, the ORR is approximately 30%, the median progression-free survival is an estimated to be 3 months, and the median overall survival ranges from 6 to 11 months.

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Teclistamab showed promising clinical activity and a tolerable safety profile in patients with relapsed/refractory multiple myeloma.

Treatment for Relapsed/Refractory Multiple Myeloma Shows Promising Clinical Activity, Safety

The FDA has granted a breakthrough therapy designation to zanidatamab for the treatment of patients with HER2 gene—amplified biliary tract cancer (BTC) who have received prior therapy. The designation is based on an ongoing phase 1 study (NCT02892123) of zanidatamab in patients with locally advanced, unresectable and/or metastatic HER2-expressing cancers, including BTC. Findings from the trial will be presented at the 2021 Gastrointestinal Cancers Symposium in January.

"This breakthrough therapy designation from the FDA, based on data generated in BTC patients treated in the initial phase 1 trial, is recognition of the potential of zanidatamab to provide a new approach to cancer treatment," said Diana Hausman, MD, chief medical officer at Zymeworks, the developer of zanidatamab. "This milestone supports our strategy for accelerated approval and will help make zanidatamab available for patients as quickly as possible."

BTC comprises approximately 3% of all adult cancers and are linked with a poor prognosis. On an international scale, 210,000 people are diagnosed with BTC annually. Additionally, at least 65% of BTCs, when diagnosed, cannot be surgically resected and those that are typically have a high recurrence rate. Current systemic options are limited for those who progress on first-line chemotherapy. 

The FDA has granted a breakthrough therapy designation to zanidatamab for the treatment of patients with HER2 gene–amplified biliary tract cancer who have received prior therapy.

Zanidatamab Gets FDA Breakthrough Designation for HER2 Gene–Amplified Biliary Tract Cancer

The FDA has approved the FoundationOne CDx (F1CDx) comprehensive genomic test as a companion diagnostic for larotrectinib (Vitrakvi) to identify patients with NTRK1/2/3 gene fusions across all solid tumors.

FoundationOne CDx is currently the sole FDA-approved tissue-based comprehensive genomic profiling assay that is indicated to detect NTRK1/2/3 fusions across all solid malignancies and identify those who may be appropriate for treatment with the TRK inhibitor. Larotrectinib is approved for the treatment of adult and pediatric patients with solid tumors that have a NTRK gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have no satisfactory alternative treatments or that have progressed following therapy.

“Taking a comprehensive and validated approach to genomic testing is critical for all advanced cancer patients, but especially for those harboring rare mutations that can be missed with alternative testing methods,” said Brian Alexander, MD, MPH, chief medical officer at Foundation Medicine. “Not only will this approval improve access to genomic testing and reinforce the role it plays in rare cancers, but it also confirms the incredible progress made toward tumor-agnostic cancer care. We’re proud of the impact this will have on NTRK fusion—positive cancer patients.”

The FDA approved larotrectinib in November 2018 based on findings from patients with TRK-positive tumors enrolled across 3 clinical trials. In results published in the 

(NEJM) in February 2018, larotrectinib induced an objective response rate (ORR) of 75% (95% CI, 61-85) by independent review and 80% (95% CI, 67-90) by investigator assessment in 55 evaluable patients. Per the independent assessment, there were 7 (13%) complete responses (CRs), 34 (62%) partial responses (PRs), and 7 (13%) patients with stable disease (SD).

FDA Approves FoundationOne CDx Genomic Test as Companion Diagnostic for Larotrectinib

The FDA has granted a fast track designation to the investigational CD20-directed monoclonal antibody ublituximab in combination with the PI3K-delta inhibitor umbralisib (U2 regimen) for the treatment of adult patients with chronic lymphocytic leukemia (CLL).

Positive topline results of the combination were unveiled in May 2020 from the phase 3 UNITY-CLL trial, in which the doublet improved progression-free survival (PFS) compared with obinutuzumab (Gazyva) plus chlorambucil in patients with previously untreated and relapsed/refractory disease.

 The study is being conducted under a Special Protocol Assessment agreement with the FDA. An independent review panel determined that the chemotherapy-free U2 combination induced a statistically significant improvement in PFS (P < .0001), and the panel recommended that the trial be stopped early.

"We are extremely pleased to have received fast track designation for the ublituximab plus umbralisib regimen, or the U2 combination, to treat adult patients with CLL. The application for Fast Track was based on data from the UNITY-CLL phase 3 study that we announced earlier this year had met its primary endpoint of progression free survival,” said Michael S. Weiss, executive chairman and chief executive officer of TG Therapeutics, the developer of both agents.

In the phase 3 UNITY-CLL trial, patients with both treatment-naïve and relapsed/refractory CLL were initially randomized into 1 of 4 treatment arms: single-agent ublituximab; single-agent umbralisib; U2; or obinutuzumab plus chlorambucil. The trial design did allow for discontinuation of the 2 monotherapy arms following a positive assessment of the U2 combination. Randomization, at that point, continued with the U2 and obinutuzumab/chlorambucil arms only.

The FDA granted fast track designation to the investigational CD20-directed monoclonal antibody ublituximab in combination with the PI3K-delta inhibitor umbralisib for the treatment of chronic lymphocytic leukemia.