The Targeted Pulse: New Standards in Myeloma, Melanoma, and More

Welcome to this week’s edition of The Targeted Pulse, our top 5 stories of the week delivered right to you. This week, we saw FDA decisions in myeloma and melanoma and compelling trial data in pancreatic cancer and leukemia. From regulatory designations for promising new drugs to crucial clinical trials, here are the top stories that shaped the week.

FDA Approves Daratumumab Quadruplet for Transplant-Ineligible Myeloma

The FDA approved subcutaneous daratumumab and hyaluronidase-fihj (Darzalex Faspro) in combination with bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (D-VRd) for patients with newly diagnosed multiple myeloma (MM) who are transplant-ineligible.

This approval, based on the phase 3 CEPHEUS trial, establishes D-VRd as a new frontline standard. The quadruplet significantly improved the primary end point of minimal residual disease (MRD) negativity (60.9% vs 39.4%; P <.0001) and reduced the risk of progression or death (HR, 0.57). Clinically, the regimen showed manageable safety, though with increased rates of grade 3/4 neutropenia (44.2%) and thrombocytopenia (28.4%) compared to VRd. Treatment discontinuations were lower in the D-VRd arm.

Atebimetinib Combo Shows Compelling 1-Year OS in First-Line Pancreatic Cancer

Updated results from the phase 2a trial of atebimetinib (IMM-1-104), a novel oral "deep cyclic" MEK inhibitor, demonstrate a 12-month overall survival (OS) rate of 64% in first-line pancreatic ductal adenocarcinoma. Combined with modified gemcitabine/nab-paclitaxel, the 320 mg daily regimen significantly exceeded the historical 35% 12-month OS benchmark.

The regimen showed a 9-month OS of 86% and progression-free survival (PFS) of 53%. Its pulsatile inhibition mechanism targets the MAPK pathway while sparing healthy cells, resulting in a manageable safety profile; only neutropenia (18%) and anemia (24%) exceeded 10% for grade 3 adverse events. A pivotal phase 3 trial (MAPKeeper 301) is scheduled for mid-2026.

Blinatumomab Plus Chemo Show Improved Survival in Infants with KMT2A-r ALL

Long-term follow-up data from a phase 2 trial demonstrate that adding a single 28-day course of blinatumomab (Blincyto) to standard Interfant-06 chemotherapy significantly improves outcomes in infants with KMT2A-rearranged (KMT2A-r) acute lymphoblastic leukemia. At a median follow-up of 4.2 years, the 4-year disease-free survival was 83.3% and OS was 93.3%, compared with historical rates of 44.0% and 60.2%, respectively.

The regimen showed high efficacy, with 93% of patients achieving MRD negativity or low levels postinfusion. Toxicity was manageable; while grade ≥3 infections occurred in 70% of patients, no infection-related deaths were reported post-induction. These findings support blinatumomab as a frontline standard for this high-risk population.

FDA Grants Fast Track Designation to IBI3003 for R/R Multiple Myeloma

The FDA granted fast track designation to IBI3003, a first-in-class trispecific T-cell engager targeting GPRC5D, BCMA, and CD3, for relapsed/refractory MM following at least 4 prior lines of therapy.

Phase 1/2 data presented at ASH 2025 demonstrated an 83.3% overall response rate (ORR) at doses at least 120 μg/kg, with 100% MRD negativity in patients achieving complete response. Notably, efficacy was maintained in patients with extramedullary disease (80% ORR) and those previously exposed to BCMA/GPRC5D therapies (77.8% ORR). The safety profile was manageable; all cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome events were grade 1/2, with no grade ≥ 3 oral toxicities reported.

FDA Clears IND for Phase 3 Trial of iSCIB1+ in Advanced Melanoma

The FDA cleared an investigational new drug application for a global, registrational phase 3 trial of iSCIB1+, a novel DNA vaccine, for the treatment of advanced melanoma.

The clearance is based on the phase 2 SCOPE trial, where adding iSCIB1+ to doublet checkpoint inhibitors (nivolumab [Opdivo]/ipilimumab [Yervoy]) yielded a 74% PFS rate at 16 months in the target HLA-positive population—significantly exceeding the historical 50% benchmark. Favorable PFS was consistent across high-risk subgroups, including BRAF wild-type and PD-L1–low disease. iSCIB1+ utilizes a needle-free delivery system to induce tumor-specific T-cell responses and is expected to move into phase 3 in 2026.