IKZF3

On February 11, 2025, the Food and Drug Administration approved brentuximab vedotin (Adcetris, Seagen Inc., a subsidiary of Pfizer) in combination with lenalidomide and a rituximab product for adult patients with relapsed or refractory large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), DLBCL arising from indolent lymphoma, or high-grade B-cell lymphoma (HGBL), after two or more lines of systemic therapy who are ineligible for autologous hematopoietic stem cell transplantation (auto-HSCT) or CAR T-cell therapy.Full prescribing information for Adcetris will be posted on Drugs@FDA. Efficacy and SafetyApproval was based on ECHELON-3 (NCT04404283), a randomized, double-blind, placebo-controlled trial enrolling 230 adult patients with relapsed or refractory LBCL who were ineligible to receive an auto-HSCT or CAR T-cell therapy. Patients were randomized 1:1 to receive brentuximab vedotin plus lenalidomide and rituximab (BV+R2) or placebo plus lenalidomide and rituximab (Pbo+R2) until disease progression or unacceptable toxicity.The major efficacy outcome measure was overall survival (OS). Additional efficacy outcome measures included progression-free survival (PFS) and objective response rate (ORR) per 2014 Lugano Criteria. The trial demonstrated a statistically significant OS improvement with a median OS of 13.8 months (95% CI: 10.3, 18.8) in the BV+R2 arm and 8.5 months (95% CI: 5.4, 11.7) in the Pbo+R2 arm (Hazard ratio [HR] 0.63, 95% CI: 0.45, 0.89; p-value 0.0085). The trial also demonstrated a statistically significant improvement in PFS and ORR. Median PFS was 4.2 months (95% CI: 2.9, 7.1) with BV+R2 and 2.6 months (95% CI: 1.4, 3.1) with Pbo+R2 (HR 0.53, 95% CI: 0.38, 0.73; p-value <0.0001). The ORR was 64.3% (95% CI: 54.7, 73.1) and 41.5% (95% CI: 32.5, 51.0), respectively.Adverse ReactionsThe most common adverse reactions (≥20%), excluding laboratory abnormalities in the BV+R2 arm were fatigue, diarrhea, peripheral neuropathy, rash, pneumonia, and COVID-19 infection. Grade 3 to 4 laboratory abnormalities occurring in more than 10% were decreased neutrophils, decreased lymphocytes, decreased platelets, and decreased hemoglobin. Peripheral neuropathy developed or worsened in 27% of patients, was predominantly sensory, and led to brentuximab vedotin dose reduction in 6% and discontinuation in 4.5%. The recommended brentuximab vedotin dose is 1.2 mg/kg up to a maximum of 120 mg in combination with lenalidomide and rituximab administered every three weeks until disease progression or unacceptable toxicity.This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.Follow the Oncology Center of Excellence on X: @FDAOncology.

On July 31, 2020, the Food and Drug Administration granted accelerated approval to tafasitamab-cxix (MONJUVI, MorphoSys US Inc.), a CD19-directed cytolytic antibody, indicated in combination with lenalidomide for adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant. The efficacy of tafasitamab-cxix with lenalidomide was evaluated in L-MIND (NCT02399085), an open label, multicenter single-arm trial in 81 patients. Patients received tafasitamab-cxix 12 mg/kg intravenously with lenalidomide (25 mg orally on days 1 to 21 of each 28-day cycle) for maximum of 12 cycles, followed by tafasitamab-cxix as monotherapy. Efficacy was based on best overall response rate (ORR), defined as complete and partial responders and response duration, as assessed by an independent review committee. The best ORR in 71 patients with a diagnosis of DLBCL confirmed by central pathology was 55% (95% CI: 43%, 67%), with complete responses in 37% and partial responses in 18% of patients. Median response duration was 21.7 months (range: 0, 24). The most common adverse reactions (≥20%) were neutropenia, fatigue, anemia, diarrhea, thrombocytopenia, cough, pyrexia, peripheral edema, respiratory tract infection, and decreased appetite. The recommended tafasitamab-cxix dose is 12 mg/kg as an intravenous infusion. View full prescribing information for MONJUVI. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application one month ahead of the FDA goal date. This application was granted priority review, fast track, breakthrough, and orphan product designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics. Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088. For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov. For information on the COVID-19 pandemic, see the following resources: FDA: Coronavirus Disease 2019 (COVID-19) NCI: Coronavirus: What People With Cancer Should Know CDC: Coronavirus (COVID-19) Follow the Oncology Center of Excellence on Twitter @FDAOncologyExternal Link Disclaimer. Content current as of: 08/03/2020 Regulated Product(s) Drugs Prescription Drugs 08/03/2020 Drugs Prescription Drugs Resources for Information | Approved Drugs Oncology (Cancer)/Hematologic Malignancies Approval Notifications Ongoing | Cancer Accelerated Approvals Verified Clinical Benefit | Cancer Accelerated Approvals Withdrawn | Cancer Accelerated Approvals Other | Cancer Accelerated Approvals Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) Short Description Oncology (Cancer)/Hematologic Malignancies Approval Notifications Ongoing | Cancer Accelerated Approvals Verified Clinical Benefit | Cancer Accelerated Approvals Withdrawn | Cancer Accelerated Approvals Other | Cancer Accelerated Approvals Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) Short Description

Nurix now plans to restart enrollment, prioritizing patients with aggressive forms of non-Hodgkin lymphoma. Nurix is hoping to continue to surf the wave of interest in its BTK degraders now that the FDA has lifted a partial hold on a phase 1 trial of a B-cell malignancy drug. The agency placed the hold in November 2023 after Nurix alerted the FDA it was planning to improve the manufacturing process for NX-2127, a small molecule that drives targeted BTK and IKZF3 degradation. The change meant that screening and enrollment of new patients for the phase 1 study in relapsed or refractory B-cell malignancies was paused. “We are pleased with the timely resolution of the partial clinical hold, which allows us to reinitiate enrollment in the NX-2127 phase 1 study utilizing drug product from our new manufacturing process,” Nurix’s Head of Clinical Development Paula O’Connor, M.D., said in a statement this morning. “Following our clinical data disclosures at the American Society of Hematology Annual Meeting last year and the recent scientific publication in the journal Science, we are seeing an acceleration of interest in our BTK degrader programs.” Nurix now plans to restart enrollment, prioritizing patients with aggressive forms of non-Hodgkin lymphoma, including diffuse large B-cell lymphoma and mantle cell lymphoma where durable complete responses have been observed. “Patients currently enrolled in the clinical study who are deriving clinical benefit from NX-2127 manufactured with the prior process may continue to receive that treatment in accordance with the study protocol,” the biotech explained. Nurix has already seen some interest from Big Pharma. Gilead Sciences bought into the first licensing option stemming from a 2019 collaboration last year, snagging exclusive rights to Nurix’s IRAK4 degrader NX-0479 in exchange for $20 million in upfront cash and $425 million in biobucks. And in September 2023, Seagen paid $60 million to Nurix to collaborate on degrader-antibody conjugates—a new class of antibody therapies that are also being pursued by the likes of Merck & Co. Nurix’s shareholders seemed relatively unfazed by the FDA’s hold in the fall and responded to today’s news with an equally negligible 1% bump in the company’s share price to $15.01 in pre-market trading Monday. Since the hold was implemented, Nurix has read out phase 1a dose escalation and phase 1b dose expansion data for NX-2127 in chronic lymphocytic leukemia, mantle cell lymphoma and diffuse large B-cell lymphoma. The drug induced “robust and sustained degradation of BTK and biologically relevant degradation of IKZF1,” according to Nurix. The biotech’s other clinical-stage BTK degrader, called NX-5948, is being studied in a phase 1 trial of adults with relapsed or refractory B-cell malignancies. Nurix expects to expand the study into patients with chronic lymphocytic leukemia and non-Hodgkin lymphoma this year.