The OncFive: Top Oncology Articles for the Week of 10/18

Welcome to OncLive®’s OncFive!

Every week, we bring you a quick roundup of the 5 top stories from the world of oncology—ranging from pivotal regulatory decisions to key pipeline updates to expert insights on breakthroughs that are moving the needle in cancer care. This resource is designed to keep you informed on the latest updates in the space, in just a matter of minutes.

Here’s what you may have missed this week:

FDA Grants Accelerated Approval to Dostarlimab (Jemperli) for dMMR/MSI-H Locally Advanced Rectal Cancer

The FDA granted accelerated approval to dostarlimab-gxly (Jemperli) for adult patients with stage II or III mismatch repair–deficient (dMMR) or microsatellite instability–high (MSI-H) locally advanced rectal cancer, as determined by an FDA-authorized test, making it the first immunotherapy approved in the US for this population. In the single-arm phase 2 AZUR-1 trial (NCT05723562), dostarlimab monotherapy given at 500 mg every 3 weeks for 9 cycles produced a 12-month sustained clinical complete response (cCR12) rate of 47% (95% CI, 27%-56%) and an overall response rate (ORR) of 79% (95% CI, 71%-85%) among patients evaluable by independent central review (ICR; n = 116), meeting the primary end point. Per investigator assessment in AZUR-1, the cCR12 rate was 68% (95% CI, 60%-76%) and the ORR was 82% (95% CI, 75%-88%); in a supporting single-arm phase 2 trial (NCT04165772; n = 50), the cCR12 rate was 93% (95% CI, 82%-99%) and the ORR was 100% (95% CI, 93%-100%). At data cutoff in AZUR-1, an additional 33% of patients had a clinical complete response per ICR with less than 12 months of follow-up and 38% had a near-complete response, while in the supporting trial, 1 of 27 patients evaluated for at least 3 years experienced a local recurrence that was managed with lymphadenectomy. The decision came ahead of a Prescription Drug User Fee Act (PDUFA) target date in February 2027, and AZUR-1 key secondary end points include clinical complete response rates at 24 and 36 months, 3-year event-free survival, and overall survival (OS).

FDA Grants Full Approval to Pembrolizumab (Keytruda) for Unresectable or Metastatic TMB-H Solid Tumors

The FDA granted traditional approval to pembrolizumab (Keytruda) and subcutaneous pembrolizumab and berahyaluronidase alfa-pmph (Keytruda Qlex) for adult and pediatric patients with unresectable or metastatic tumor mutational burden–high (TMB-H) solid tumors, as determined by an FDA-authorized test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. The approval converts the June 2020 accelerated approval and redefines TMB-H as at least 13 mutations per megabase, up from the prior threshold of 10 mutations per megabase, as the FDA determined that efficacy data did not support full approval for tumors with 10 to fewer than 13 mutations per megabase. In the phase 2 KEYNOTE-158 trial (NCT02628067), the ORR among 220 patients with TMB-H tumors (cohort M, n = 145; cohorts A-J, n = 75) was 36% (95% CI, 30%-43%), and 58% of responders had a duration of response lasting at least 12 months. Safety was consistent with the known profile of pembrolizumab monotherapy, with the most common adverse effects (≥20%) including fatigue, musculoskeletal pain, rash, diarrhea, pyrexia, cough, decreased appetite, pruritus, dyspnea, constipation, abdominal pain, nausea, and hypothyroidism. The recommended dosing is 200 mg every 3 weeks or 400 mg every 6 weeks in adults and 2 mg/kg (up to 200 mg) every 3 weeks in pediatric patients, for up to 24 months or until disease progression or unacceptable toxicity; KEYNOTE-158 did not enroll patients with melanoma or non–small cell lung cancer.

Teclistamab (Tecvayli) Monotherapy Wins EU Approval for Relapsed/Refractory Myeloma After At Least 1 Prior Therapy

The European Commission approved teclistamab (Tecvayli) monotherapy for adult patients with relapsed/refractory multiple myeloma who have received at least 1 prior therapy, moving the agent into the second-line setting after its August 2022 approval in patients with at least 3 prior therapies and an August 2026 EU approval of teclistamab plus daratumumab (Darzalex) in the same population. In the phase 3 MajesTEC-9 trial (NCT05572515), teclistamab (n = 296) reduced the risk of disease progression or death by 71% vs investigator’s choice of pomalidomide, bortezomib, and dexamethasone or carfilzomib and dexamethasone (n = 297) at a median follow-up of 17.3 months, with estimated 18-month progression-free survival (PFS) rates of 69.8% vs 26.9%, respectively (hazard ratio [HR], 0.29; 95% CI, 0.23-0.38; P < .001). Median PFS was not reached with teclistamab vs 8.2 months with the control regimens, 18-month OS rates were 79.2% vs 68.6% (HR, 0.60; 95% CI, 0.43-0.83; P = .002), and the ORR was 84.5% vs 54.2%, with complete response (CR) or better rates of 65.9% vs 16.8% and measurable residual disease (MRD)–negative CR or better rates (10⁻⁵) of 38.5% vs 6.7%. Grade 3/4 treatment-emergent adverse effects (TEAEs) occurred in 84.9% vs 76.3% of patients; in the teclistamab arm, cytokine release syndrome occurred in 66.0% of patients (nearly all grade 1/2, with no grade 4/5 events) and immune effector cell–associated neurotoxicity syndrome occurred in 4.1% (grade 3, 0.3%), and grade 5 infections occurred in 5.5% vs 2.8% of patients, respectively. Grade 3/4 neutropenia (54.3% vs 22.3%) and hypogammaglobulinemia (69.1% vs 50.2%) were more frequent with teclistamab, and investigators recommended antimicrobial prophylaxis and immunoglobulin replacement, while the PFS benefit was consistent across prespecified subgroups, including anti-CD38–refractory, lenalidomide-refractory, high-risk cytogenetic, and 1-prior-line disease.

FDA Accepts NDA for UGN-103 in Recurrent Low-Grade Intermediate-Risk NMIBC

The FDA accepted a new drug application (NDA) for UGN-103 (mitomycin) intravesical solution for the treatment of adult patients with recurrent low-grade, intermediate-risk non–muscle-invasive bladder cancer (NMIBC), and a PDUFA target action date of June 14, 2027, has been set. The NDA is supported by the single-arm, open-label phase 3 UTOPIA trial (NCT06331299; n = 99), in which UGN-103 produced a 3-month CR rate of 77.8% (95% CI, 68.3%-85.5%), and the Kaplan-Meier–estimated probability of remaining event-free at 6 months among patients with a CR was 94.5%. UGN-103 incorporates mitomycin into a thermally responsive hydrogel (RTGel) that is liquid when chilled and forms a semisolid gel depot after instillation, and it was administered at 75 mg once weekly for 6 weeks to patients with low-grade Ta NMIBC with at least 1 prior NMIBC episode and intermediate-risk features. Among 99 treated patients, TEAEs occurred in 59.6%, serious TEAEs occurred in 2 patients (2.02%), TEAEs of special interest occurred in 37.4%, and no adverse effects led to death. The sponsor’s related formulation UGN-102 (Zusduri) was approved by the FDA in June 2025 for the same population based on the phase 3 ENVISION trial (NCT05243550), and the UTOPIA safety findings were reported as consistent with ENVISION data.

Lisaftoclax Plus Acalabrutinib (Calquence) Receives Breakthrough Therapy Designation in China for Treatment-Naive CLL/SLL

The Center for Drug Evaluation of China’s National Medical Products Administration (NMPA) granted breakthrough therapy designation to lisaftoclax (APG-2575) plus acalabrutinib (Calquence) for the treatment of adult patients with treatment-naive chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). The combination is under evaluation in the global, registrational phase 3 GLORA-2 trial (NCT06319456), which is comparing fixed-duration lisaftoclax at 600 mg daily plus acalabrutinib at 100 mg twice daily for up to 18 cycles vs fludarabine, cyclophosphamide, and rituximab or chlorambucil plus rituximab for 6 cycles in patients with newly diagnosed CLL/SLL who meet at least 1 2018 International Workshop on Chronic Lymphocytic Leukemia treatment criterion and have an Eastern Cooperative Oncology Group performance status of 0 to 2. PFS is the primary end point of GLORA-2, and secondary end points include ORR, MRD negativity in bone marrow and/or peripheral blood, TEAEs, and treatment-related adverse effects. Ascentage Pharma noted that immunochemotherapy has limited efficacy in high-risk patients, including those with del(17p) or TP53 mutations, complex karyotype, or unmutated IGHV, and that continuous Bruton tyrosine kinase (BTK) inhibitor monotherapy may not achieve sufficient depth of response. Lisaftoclax, an oral, selective BCL-2 inhibitor, was approved by the NMPA in July 2025 for adults with CLL/SLL previously treated with at least 1 systemic therapy including a BTK inhibitor, and the global phase 3 GLORA trial (NCT06104566) is evaluating lisaftoclax plus a BTK inhibitor in patients with a suboptimal response after more than 12 months of BTK inhibitor therapy; the combination is not approved in any market, and lisaftoclax remains investigational in the US.