Onivyde (nanoliposomal irinotecan) / Servier, Ipsen, PharmaEngine - LARVOL DELTA

NALIRIFOX versus liposomal irinotecan plus fluorouracil/leucovorin as the second-line chemotherapy in gemcitabine refractory pancreatic adenocarcinoma: a real-world study. (PubMed, Ther Adv Med Oncol) - "Although nanoliposomal irinotecan plus oxaliplatin, fluorouracil, and leucovorin (NALIRIFOX) has shown superior efficacy as first-line therapy over gemcitabine and nab-paclitaxel, its roles as second-line therapy remains undefined. NALIRIFOX provides superior PFS compared to nal-IRI/FL as second-line therapy for advanced or metastatic pancreatic cancer after gemcitabine failure. Although NALIRIFOX was associated with higher rates of hematologic and neurologic toxicities, they were manageable with careful monitoring."

Journal • Real-world evidence • Febrile Neutropenia • Hematological Disorders • Neutropenia • Oncology • Pain • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • Thrombocytopenia

Poly(ethylene Glycol) Densities Determine the Mechanism of the Accelerated Blood Clearance of PEGylated Liposomes. (PubMed, Biomacromolecules) - "Polyethylene glycol (PEG) is used to graft liposomes with different densities to enhance their colloidal stability or blood circulation time, such as 0.3 mol % for commercial Onivyde and 5 mol % for DOXIL. Therefore, preinjecting a low dose of PEG completely inhibits the ABC of 0.3 mol % PEGylated liposomes while only partially decreasing the ABC of 5 mol % PEGylated liposomes in the PEG-immunized rats. These results suggest that the interfacial PEG density determines the mechanism of the ABC phenomenon of PEGylated liposomes, and the ABC of Onivyde can be readily inhibited by removing high-affinity anti-PEG antibodies in blood through preinjection of a low dose of PEG."

Journal

NALIRIFOX versus nab-paclitaxel and gemcitabine in older patients with treatment-naive metastatic pancreatic cancer: a subgroup analysis of the pivotal NAPOLI 3 trial. (PubMed, ESMO Open) - "NALIRIFOX improved mPDAC survival versus Gem + NabP irrespective of patient age, with no signals for reduced tolerability in the older (versus younger) patients. The results provide reassurance that triplet therapy with NALIRIFOX is an efficacious and tolerable regimen in older treatment-naive patients with mPDAC who were fit enough for inclusion in NAPOLI 3, supporting consideration of its use as 1L therapy in this population."

Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Second-line chemotherapy after gemcitabine plus nab-paclitaxel in metastatic pancreatic cancer: comparative outcomes and AI-guided treatment selection. (PubMed, Oncologist) - "FOLFIRINOX appears the most effective option for carefully selected, fit patients eligible for 2L chemotherapy after GnP failure. Interpretable artificial intelligence-derived treatment policies may provide superior net clinical benefit compared to uniform approaches and guide individualized therapy, warranting integration with upcoming targeted strategies such as RAS inhibitors."

Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CA 19-9

Optimized dose schedule of rucaparib and liposomal irinotecan/5-fluorouracil in metastatic gastrointestinal cancers: A phase 1 study. (PubMed, Cancer) - "This optimized dosing schedule successfully established the MTD for RUB with nal-IRI and 5-FU, overcoming prior challenges with PARP inhibitor and irinotecan combinations. The promising ORR and DCR support further evaluation of this regimen in advanced GI malignancies."

Journal • P1 data • Gastrointestinal Cancer • Hematological Disorders • Neutropenia • Oncology • Solid Tumor • ATM • BRCA • HRD

Liposomal irinotecan, carboplatin or oxaliplatin (LyRICX) with or without nivolumab in the first-line treatment of metastatic or irresectable esophagogastric adenocarcinoma: A randomized phase 2 study. (ASCO-GI 2026) - "Until August 2022, patients were randomized (2:2:1) to one of three arms: 1) nanoliposomal irinotecan, leucovorin and fluorouracil (F-Nal-Iri); 2) capecitabine and carboplatin (CapCar); 3) capecitabine and oxaliplatin (CapOx). Relative to CapOx, CapCar and F-Nal-Iri yielded markedly lower rates of grade 2-4 neurotoxicity with similar PFS and no excess of other toxicities. Given its ease of use—no central line required—and its relatively low cost (all drugs off-patent), CapCar can be considered the most favorable first-line chemotherapy backbone."

Clinical • Late-breaking abstract • Metastases • P2 data • Esophageal Cancer • Gastric Adenocarcinoma • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2

Single protein encapsulated SN38: Extremely effective anticancer drug with low toxicity (AACR 2026) - "At present, only prodrug approach on SN38 has resulted in 2 types of therapeutics approved by the FDA, irinotecan/ONIVYDE and Trodelvy. SPESN38 complexes provide a novel water soluble SN38 formulation. SPESN38‑5 and SPESN38‑8 demonstrate better PK values, lower toxicity and superior antitumor efficacy in mouse models, compared with irinotecan, DOX and Doxil. FDA has green-lighted SPESN38-8 (IND #: 164346) for clinical development."

Colorectal Cancer • Ewing Sarcoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

SCRT-NALIRIXELOX+Sintilimab as TNT for High-Risk LARC (clinicaltrials.gov) - P=N/A | N=49 | Recruiting | Sponsor: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

New trial • Colorectal Cancer • Oncology • Rectal Adenocarcinoma • Rectal Cancer • Solid Tumor

A Study of Suizenji in Patients With Unresectable Pancreatic Cancer (clinicaltrials.gov) - P=N/A | N=90 | Active, not recruiting | Sponsor: SONIRE Therapeutics Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Sep 2026 ➔ May 2027 | Trial primary completion date: Sep 2026 ➔ May 2027

Enrollment closed • Trial completion date • Trial primary completion date • Oncology • Pancreatic Cancer • Solid Tumor

Development of an In Vitro Release Test to Characterize Onivyde® Using Bio-Beads SM-2 Resin. (PubMed, AAPS J) - "Compared to dialysis-based approaches, this method more effectively maintains sink conditions, eliminates membrane-related diffusion limitations, and simplifies sample handling by avoiding separation steps. Overall, the BioBeads-based IVRT offers a practical, robust, and sensitive platform for accelerated release testing and quality control of liposomal irinotecan, with strong potential for use in generic drug development and regulatory evaluation."

Journal • Preclinical

PANORAMIX G-116: Pancreatic cancer first-line NALIRIFOX optimization with 5-FU maintenance and role of antibiotics and microbiota exploration in second-line treatment A non-comparative, randomized phase II PANORAMIX GERCOR G-116 PRODIGE 105 study (clinicaltrialsregister.eu) - P1/2 | N=142 | Recruiting | Sponsor: Association Gercor | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Pancreatic Cancer • Solid Tumor

FOLFIRINOX vs. Gemcitabine/Nab-Paclitaxel for Pancreatic Cancer by BRCA2 and TMB Status: A Japanese C-CAT Database Study. (PubMed, Cancer Sci) - "Among patients with BRCA2 PVs treated with GnP, OS was numerically longer with second-line FFX than with nal-IRI/5-FU/leucovorin (HR 0.51; p = 0.119)...In BRCA2 PV tumors, greater tumor shrinkage with first-line FFX did not translate into longer OS, underscoring the importance of sequencing strategies that ensure timely exposure to platinum-based therapy. TMB-high tumors may benefit from timely access to immunotherapy."

IO biomarker • Journal • Tumor mutational burden • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • BRCA2 • TMB

A Study to Evaluate the Effectiveness and Safety of Setidegrasib, Given With Either mFOLFIRINOX or NALIRIFOX Chemotherapies, in People With Pancreatic Cancer (clinicaltrials.gov) - P3 | N=614 | Recruiting | Sponsor: Astellas Pharma Global Development, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • KRAS

NEO-Nal- IRI: A Study of the Safety and Activity of Liposomal Irinotecan in Combination With the 5-FU and Oxaliplatin in the Preoperative Treatment of Pancreatic Adenocarcinoma (clinicaltrials.gov) - P2 | N=45 | Active, not recruiting | Sponsor: University of Florida | Trial completion date: Feb 2026 ➔ Dec 2026

Trial completion date • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • CA 19-9 • UGT1A1

Markers of immune activation and immunotherapy responsiveness are increased in 3D Pancreatic cancer organoids when primed with photodynamic- and chemo-therapy. (PubMed, Transl Oncol) - "The organoids reproduced key features of pancreatic tumors and showed strong resistance to chemotherapy (nanoliposomal irinotecan, nal-IRI) and immune checkpoint inhibitor (anti-PD-1) when used alone...Together, these findings show that PDP remodels the pancreatic tumor microenvironment, enhances chemotherapy efficacy, and sensitizes tumors to immune checkpoint inhibitors. This strategy uses clinically approved agents and offers a promising, translatable approach to overcoming treatment resistance in pancreatic cancer."

IO biomarker • Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Studying Chemotherapy With or Without Panitumumab for Unresectable, Locally Advanced, or Metastatic Pancreatic Cancer Without KRAS Mutations (clinicaltrials.gov) - P3 | N=94 | Recruiting | Sponsor: SWOG Cancer Research Network | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • ALK • BRAF • BRCA1 • BRCA2 • EGFR • KRAS • MSI • NRAS • NRG1 • NTRK1 • TMB

Nal-IRI/5-FU/LV Chemotherapy Combined With PD-L1 Inhibitor and Multi-target Anti-angiogenic Small Molecule±SBRT as Second-line Therapy in Metastatic Pancreatic Cancer Patients (clinicaltrials.gov) - P2 | N=56 | Recruiting | Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Pancreatic Cancer • Solid Tumor

Unveiling the hidden risks of nanomedicine-based drug delivery: a comparative evaluation of drug safety profiles of liposomal irinotecan and conventional irinotecan. (PubMed, Nanotoxicology) - "Nal-IRI demonstrates distinct safety challenges, including delayed toxicity, hepatobiliary risks, and population-specific vulnerabilities. These findings have revealed the unique risks associated with nanomedicine, underscoring the necessity extending pharmacovigilance."

Journal • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hepatology • Neutropenia • Oncology • Pain

A Study to Confirm the Safety of ASP3082, and if it Delays Tumor Growth in People With Pancreatic Cancer, When Given With Either mFOLFIRINOX or NALIRIFOX Chemotherapies (clinicaltrials.gov) - P3 | N=614 | Not yet recruiting | Sponsor: Astellas Pharma Global Development, Inc.

New P3 trial • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • KRAS

Mechanistic PBPK/PD modeling of free and nano-liposomal irinotecan reveals formulation-specific determinants of disposition and efficacy. (PubMed, Int J Pharm) - "Nal-IRI achieved sustained and higher SN-38 tumor exposure, producing more rapid and durable tumor suppression than free-IRI. This integrated PBPK/PD framework provides mechanistic insights into the enhanced efficacy of nal-IRI and supports its optimized use in irinotecan-based cancer therapy."

Journal • Lung Cancer • Oncology • Pediatrics

CLARITY-PanTumor01: AZD0901 in Participants With Advanced Solid Tumours Expressing Claudin18.2 (clinicaltrials.gov) - P2 | N=224 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Dec 2026 ➔ Sep 2027 | Trial primary completion date: Dec 2025 ➔ Aug 2026

Monotherapy • Pan tumor • Trial completion date • Trial primary completion date • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Esophageal Cancer • Gallbladder Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CLDN18

ONITT: Study of Onivyde With Talazoparib or Temozolomide in Children With Recurrent Solid Tumors and Ewing Sarcoma (clinicaltrials.gov) - P1/2 | N=90 | Recruiting | Sponsor: St. Jude Children's Research Hospital | Trial completion date: Dec 2025 ➔ Dec 2026

Trial completion date • Embryonal Tumor • Ewing Sarcoma • Germ Cell Tumors • Hepatoblastoma • Nephrology • Neuroblastoma • Oncology • Osteosarcoma • Rhabdoid Tumor • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Wilms Tumor • EWSR1 • FLI1

NIOFA-02: A Randomized, Open-Label Cohort Study of Adebrelimab Combined with NALIRIFOX or Gemcitabine-Cisplatin (GC) as First-Line Treatment for Locally Advanced or Metastatic Biliary Tract Cancer (ChiCTR) - P4 | N=102 | Not yet recruiting | Sponsor: West China Hospital, Sichuan University; West China Hospital, Sichuan University

New P4 trial • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Gallbladder Cancer • Oncology • Solid Tumor

Safety and Efficacy of Concomitant Administration of Nanoliposomal Irinotecan + 5-Fluorouracil/Levo-Leucovorin for Pancreatic Cancer. (PubMed, Cancer Rep (Hoboken)) - "Concomitant administration of Levo-LV with nal-IRI may not increase adverse events or impact efficacy compared to sequential administration."

Journal • Oncology • Pancreatic Cancer • Solid Tumor

Long-term survival in patients with pancreatic cancer treated with second-line liposomal irinotecan plus 5-fluorouracil/leucovorin: observations from Korea, Italy, and Germany. (PubMed, ESMO Gastrointest Oncol) - "Liposomal irinotecan in combination with 5-fluorouracil and leucovorin (nal-IRI+5-FU/LV) is the only approved therapy for metastatic PAC following gemcitabine-based therapy, based on the survival benefit demonstrated in the phase III NAPOLI-1 trial. Factors such as patient age and number of previous lines of treatment that were not identified in the NAPOLI-1 nomogram may be associated with long-term survival with nal-IRI+5-FU/LV in the real-world. In conclusion, this review has shown that while prognostic factors are useful for patient stratification, their predictive value on the efficacy of nal-IRI+5-FU/LV is low, thus this treatment may also result in long-term survival in patients with apparently unfavorable characteristics."

Journal • Review • Oncology • Pancreatic Cancer • Solid Tumor • CA 19-9