Melflufen (melphalan flufenamide) / Oncopeptides, SCBIO - LARVOL DELTA

Impact of Prior Daratumumab or Isatuximab: An Analysis of Relapsed and Refractory Multiple Myeloma (RRMM) Patients Treated with Melflufen Plus Dexamethasone in the OP-106 HORIZON Study (IMS 2026) - "OP-106 HORIZON study was a multicenter, single-arm Phase II trial evaluating melphalan flufenamide (melflufen) plus dexamethasone (dex) in RRMM pts with ≥2 prior lines, refractory to pomalidomide and/or an anti-CD38 mAb, and where most pts had TCR disease (76%). Melflufen plus dex has shown clinically meaningful activity in heavily pretreated RRMM. This analysis suggests that type of prior anti-CD38 therapy may potentially impact the effect of later treatments and patterns of relapse. In the limited group of pts previously exposed to ISA, ORR, DOR, PFS and OS where numerically higher and may suggest better response to melflufen compared to pts with prior DARA exposure, despite having higher risk disease and older age."

Clinical • Hematological Malignancies • Multiple Myeloma

Efficacy and safety of melflufen plus daratumumab and dexamethasone in relapsed/refractory multiple myeloma: results from the randomized, open-label, phase III LIGHTHOUSE study. (PubMed, Haematologica) - P3 | "The most common grade ≥3 treatment-emergent adverse events in the melflufen group versus daratumumab group were neutropenia (50% versus 12%), thrombocytopenia (50% versus 8%), and anemia (32% versus 19%). Melflufen plus daratumumab and dexamethasone demonstrated superior PFS and ORR versus daratumumab in RRMM and a safety profile comparable to previously published melflufen studies."

Journal • P3 data • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Neutropenia • Oncology • Thrombocytopenia • Transplantation

Oncopeptides to highlight clinical progress and present new data at the IMS Annual Meeting (Oncopeptides Press Release) - "For the congress, a poster evaluation titled: 'Impact of prior Daratumumab or Isatuximab: an analysis of relapsed and refractory multiple myeloma (RRMM) patients treated with melflufen plus dexamethasone in the OP-106 HORIZON study' has been accepted. Led by prominent international investigators, the analysis explores clinical outcomes among heavily pretreated patients stratified by prior anti-CD38 monoclonal antibody exposure, offering further hypothesis-generating insights into treatment sequencing in modern clinical practice."

P2 data • Multiple Myeloma

Alkylating Peptide-Drug Conjugates in Glioblastoma - Towards Translational Assessment (EANO 2026) - "Standard care (surgery followed by temozolomide with radiotherapy) provides modest benefit and is less effective in tumors with high MGMT expression. These studies show that intravenous melflufen and OPD5 can penetrate the BBB and achieve intratumoral enrichment. The apparent MGMT‑independent activity suggests potential to address an important resistance mechanism. A window‑of‑opportunity study will test translational relevance by linking human exposure (PK) to early tissue responses (PD)."

Brain Cancer • Glioblastoma • Hematological Malignancies • Multiple Myeloma • Oncology • Solid Tumor • MGMT

Mitochondrial DNA Damage Contributes to the Cytotoxic Effect of Lipophilic Alkylating Peptide-Drug Conjugates (EANO 2026) - "Screening drug response in GB cell cultures, representing all subtypes, and in ex vivo patient tissue, alkylkating PDCs show superior response compared to other alkylators, including temozolomide...Material and PDCs, including melflufen and OPD5, and their metabolites were analyzed for cellular and mitochondrial localization in cancer cells and isolated mitochondria...PDCs induced similar damage to both nuclear and mitochondrial DNA, a feature not observed with other compounds utilizing the same cytotoxic payload (melphalan and cyclophosphamide)... Alkylating PDCs target mitochondria and induce mitochondrial DNA damage that contributes to its cytotoxic mechanism. Dual targeting of nuclear and mitochondrial DNA is a plausible explanation for the observation that alkylating PDCs overcome resistance mediated by cell cycle regulation and DNA repair pathways. This could be of special importance in GB since GB cells are more reliant on mitochondria for its energy production,..."

Brain Cancer • Glioblastoma • Oncology • Solid Tumor

Tumor-homing peptides in precision oncology: Mechanisms, design and recent advances. (PubMed, J Control Release) - "We analyze the structural and functional biology of the predominant internalization pathways like the Neuropilin-1 (NRP-1) dependent C-end Rule (CendR) and the Sortilin (SORT1) scavenger receptor, and their use to promote deep tissue penetration. Finally, we assess the translational landscape of early 2026, including the recent FDA withdrawal of the lipophilic peptide-conjugated melphalan flufenamide (Pepaxto®) and the recent clinical success of the cyclic peptide certepetide for pancreatic adenocarcinoma and the ongoing promising studies with chemically constrained bicyclic peptides."

Journal • Review • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • Targeted Protein Degradation • NRP1 • SORT1

Oncopeptides AB…announces that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending an extension of the therapeutic indication for Pepaxti (melflufen) to earlier lines of therapy (Oncopeptides Press Release) - "The positive opinion will now be referred to the European Commission (EC) for a final decision. Under the adopted opinion, the CHMP recommends expanding the therapeutic indication of Pepaxti, in combination with dexamethasone, to adult patients with multiple myeloma who have received at least two prior lines of therapies (third line and later), and whose disease is refractory to lenalidomide and the last line of therapy....The recommendation is based on clinical evidence from the Phase 3 OCEAN trial, which demonstrated efficacy and safety in patients with relapsed and refractory multiple myeloma (RRMM)."

CHMP • Multiple Myeloma

Comment on "Exceptional long-term responses from OCEAN and HORIZON trials: melflufen-dexamethasone as an expansion of treatment options for relapsed/refractory multiple myeloma in the era of new immunotherapies?". (PubMed, J Cancer Res Clin Oncol) - No abstract available

Journal • Hematological Malignancies • Multiple Myeloma • Oncology

Benefit Versus Risk Assessment of Melflufen and Dexamethasone in Relapsed/Refractory Multiple Myeloma: Analyses From Longer Follow-up of the OCEAN and HORIZON Studies. (PubMed, Clin Lymphoma Myeloma Leuk) - P2, P3 | "These analyses demonstrate a consistent benefit for melflufen and dexamethasone in patients with relapsed/refractory multiple myeloma who have not received an ASCT or progressed >36 months after receiving an ASCT (ClinicalTrials.gov identifier: NCT03151811)."

Journal • Bone Marrow Transplantation • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

Peptide-Drug Conjugates for Targeted Delivery in Hematological Malignancies: From Design Principles to Clinical Application. (PubMed, Pharmaceutics) - "We further discussed emerging strategies such as cathepsin B-responsive PROTAC-PDC hybrids, nanotechnology-assisted delivery, and artificial intelligence-guided molecular design. Finally, we addressed key translational challenges, including tumor heterogeneity, payload resistance, and pharmacokinetic constraints, and proposed future directions toward biomarker-driven precision PDC therapy for hematological malignancies."

IO biomarker • Journal • Review • Acute Myelogenous Leukemia • B Cell Non-Hodgkin Lymphoma • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Myelodysplastic Syndrome • Non-Hodgkin’s Lymphoma • Oncology • Targeted Protein Degradation • CTSB

NET-MS: No Evidence Of Disease Activity After Autologous Haematopoietic Stem Cell Transplantation In Aggressive Multiple Sclerosis (clinicaltrialsregister.eu) - P1/2 | N=90 | Completed | Sponsor: Fondazione Italiana Sclerosi Multipla Ente Del Terzo Settore/et S | Recruiting ➔ Completed

Trial completion • CNS Disorders • Multiple Sclerosis • Transplantation

MARINA: A Non-interventional Study of Melphalan Flufenamide (Melflufen) (Pepaxti®) and Dexamethasone in Patients With Relapsed and/or Refractory Multiple Myeloma (R/RMM) (clinicaltrials.gov) - P=N/A | N=50 | Recruiting | Sponsor: iOMEDICO AG | Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Malignancies • Multiple Myeloma • Oncology

LAGOON (OP-115): A NON-INTERVENTIONAL STUDY OF MELPHALAN FLUFENAMIDE (MELFLUFEN) PLUS DEXAMETHASONE IN PATIENTS WITH RELAPSED AND/OR REFRACTORY MULTIPLE MYELOMA IN SPAIN ACCORDING TO APPROVED LABEL (EHA 2026) - "As patients in clinical trials are often younger and have fewer comorbidities than the general MM population, real ‑ world evidence is essential to understand treatment outcomes in routine practice. The study is funded by Oncopeptides AB."

Clinical • IO biomarker • Observational data • Hematological Malignancies • Multiple Myeloma

MAINTAINED RENAL FUNCTION WITH MELFLUFEN THERAPY IN RRMM: RESULTS FROM ANALYSIS OF POOLED CLINICAL DATA (EHA 2026) - "eGFR values from baseline to Day 1 in Cycle 7 in patients treated with melflufen + dexamethasone or pomalidomide + dexamethasone. Mean and 95% confidence intervals."

Clinical data • Acute Kidney Injury • Hematological Malignancies • Multiple Myeloma • Nephrology • Neutropenia • Renal Disease • Thrombocytopenia

MITOCHONDRIAL DNA DAMAGE CONTRIBUTES TO THE CYTOTOXIC EFFECT OF THE PEPTIDE–DRUG CONJUGATE MELFLUFEN (EHA 2026) - "Melflufen induced damage to both nuclear and mitochondrial DNA, a feature not observed with other alkylators, such as melphalan and cyclophosphamide. Dual targeting of nuclear and mitochondrial DNA may allow melflufen to overcome resistance mediated by cell cycle regulation and DNA repair pathways. These findings highlight mitochondrial involvement as an important component of the activity against myeloma by melflufen and support further exploration of PDC compounds as modulators of mitochondrial vulnerability in cancer."

Hematological Malignancies • Metabolic Disorders • Multiple Myeloma

MELFLUFEN TREATMENT MAY BE PARTICULARLY EFFECTIVE IN IMMUNOCOMPROMISED PATIENTS WITH MULTIPLE MYELOMA (EHA 2026) - "Figure 1. Melflufen HS samples demonstrates lower abundance of CD8+ effector cells in flow (A) and scRNAseq (B) cohorts and higher exhaustion for HS group (C)."

Clinical • IO biomarker • Hematological Malignancies • Multiple Myeloma • CD8 • HAVCR2 • TIGIT

Real-World Outcomes of Melflufen Plus Dexamethasone in Heavily Pretreated Relapsed/Refractory Multiple Myeloma After Exposure to Immunotherapies. (PubMed, Clin Lymphoma Myeloma Leuk) - "One patient discontinued due to severe thrombocytopenia and bleeding, and one died of sepsis This is the first real-world report of melf-dex after novel immunotherapies, showing efficacy consistent with clinical trials. Melf-dex may be a valuable treatment option in very late relapse, although larger cohorts of patients and longer follow-up are needed."

Journal • Real-world evidence • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Oncology • Plasmacytoma • Septic Shock • Thrombocytopenia

BRIDGE (OP-107): A Phase 2 Pharmacokinetic Study of Melflufen Plus Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma and Impaired Renal Function. (PubMed, Clin Lymphoma Myeloma Leuk) - "PK results from the BRIDGE study support the recommended dose of melflufen 30 mg for moderate RI patients. No new safety signals were reported in RRMM patients with moderate-to-severe RI."

Journal • P2 data • PK/PD data • Hematological Malignancies • Multiple Myeloma • Oncology • Renal Disease

Melflufen in Multiple Myeloma: Clinical Limitations, Biological Rationale, and Future Perspectives. (PubMed, Cancers (Basel)) - "In this review, we examine the biological rationale, clinical development, and regulatory trajectory of melflufen, and critically reassess its role within the evolving therapeutic landscape of MM. While the negative survival findings observed in the phase III OCEAN trial substantially limited the clinical development of melflufen, the biological principles underlying enzyme-targeted intracellular drug delivery may still provide relevant insights for biomarker-driven therapeutic strategies and future peptide-drug conjugate development in MM."

Journal • Review • Hematological Malignancies • Multiple Myeloma • Oncology

Oncopeptides AB: Oncopeptides presents new clinical and preclinical melflufen data at the upcoming European Hematology Association meeting (Oncopeptides Press Release) - "The clinical data presentation contains interim results from the phase 2 BRIDGE study supporting the use of melflufen in relapsed refractory multiple myeloma patients with moderately impaired renal function. Two preclinical data presentations show the future potential of melflufen in treatments of other hematological diseases outside multiple myeloma."

P2 data • Preclinical • Acute Myelogenous Leukemia • Diffuse Large B Cell Lymphoma • Multiple Myeloma

Observing melflufen in clinical practice: the LAGOON study (TradingView) - "Furthermore, a poster regarding LAGOON (OP-115), a prospective, non-interventional study (NIS) currently being conducted in Spain, is presented. The study aims to observe the effectiveness and safety of Pepaxti in combination with dexamethasone when used in accordance with the approved label in standard clinical practice...LAGOON is enrolling 50 adult patients with RRMM who have received at least three prior lines of therapy. The study will track outcomes such as overall response rate (ORR), progression-free survival (PFS), safety and tolerability and overall survival (OS), providing vital data on how melflufen performs within the current European treatment landscape."

Real-world • Multiple Myeloma

Real-World evidence: The Spanish Registry (TradingView) - "Response rates: The ORR was 40% for the full cohort and increased to 45.4% for patients previously exposed to novel immunotherapies; Bridge to CAR-T: Notably, melflufen served as an effective bridge to CAR-T therapy for two patients, both of whom achieved a partial response; Survival outcomes: Despite the heavily pretreated nature of this cohort—where 57% of patients were penta-refractory and had received a median of 4–5 prior lines of therapy – the study reported a median progression-free survival (mPFS) of 4.2 months and a median overall survival (mOS) of 12.3 months. This is in line with the HORIZON study where ORR was 29% mPFS was 4.2 months, and mOS was 11.6 months."

Real-world evidence • Multiple Myeloma

Maintained renal function in RRMM (TradingView) - "Another highlight at COMy focuses on pooled data from three clinical studies (the Phase 1/2 O-12-M1, Phase 2 HORIZON, and Phase 3 OCEAN trials), assessing the impact of melflufen on renal function in 430 patients....The analysis demonstrates that renal function remained stable throughout melflufen treatment, and that renal adverse events were uncommon, reinforcing that melflufen can be safely administered to RRMM patients with mild to moderate renal impairment."

Retrospective data • Multiple Myeloma

OP-701: A study to investigate how a single dose of the drug melflufen reaches brain tumor tissue, and how it affects the tumour, in patients who are already scheduled for surgery for a returning glioblastoma (clinicaltrialsregister.eu) - P1 | N=10 | Not yet recruiting | Sponsor: Oncopeptides AB

New P1 trial • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

MARINA: A Non-interventional Study of Melphalan Flufenamide (Melflufen) (Pepaxti®) and Dexamethasone in Patients With Relapsed and/or Refractory Multiple Myeloma (R/RMM) (clinicaltrials.gov) - P=N/A | N=50 | Not yet recruiting | Sponsor: iOMEDICO AG

New trial • Hematological Malignancies • Multiple Myeloma • Oncology