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

Impact of Liposomal Irinotecan Availability on Real-World Survival Outcomes in Advanced Pancreatic Cancer (IASGO 2026) - "Background : Liposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin is a standard subsequenttreatment option for advanced pancreatic cancer...Among patients who received third-line nal-IRI, overallsurvival (OS) was compared according to prior chemotherapy sequence: gemcitabine/nab-paclitaxelfollowed by FOLFIRINOX versus the reverse sequence...Among patients who received third-line nal-IRI, overallsurvival (OS) was compared according to prior chemotherapy sequence: gemcitabine/nab-paclitaxelfollowed by FOLFIRINOX versus the reverse sequence...These findings suggest that access to nal-IRI as asubsequent treatment option improves survival outcomes in routine clinical practice. In addition, priorchemotherapy sequence may also influence long-term survival outcomes, warranting furtherinvestigation."

Clinical • Metastases • Real-world • Real-world evidence • Oncology • Pancreatic Cancer • Solid Tumor

NET-02: A multicenter, randomized, phase II trial of liposomal irinotecan (nal-IRI) and 5-fluorouracil (5-FU)/folinic acid or docetaxel as second-line therapy in patients (pts) with progressive poorly differentiated extra-pulmonary neuroendocrine carcinoma (PD-EP-NEC). (ASCO 2022) - "A recognised first-line (1L) treatment for advanced disease is etoposide/platinum-based chemotherapy; there is no standard second-line (2L) treatment (area of unmet need). nal-IRI/5-FU, but not docetaxel, met the primary endpoint (exceeding the threshold for efficacy), with manageable toxicity, and warrants evaluation in a phase III trial."

Clinical • P2 data • Endocrine Cancer • Gastrointestinal Disorder • Neuroendocrine Tumor • Oncology • Solid Tumor

A phase II multicenter study of NASOX regimen as adjuvant chemotherapy for patients with resected pancreatic ductal adenocarcinoma. (ASCO 2026) - P=N/A | "The PRODIGE 24/CCTG PA.6 trial demonstrated that the mFOLFIRINOX regimen significantly improved outcomes compared with gemcitabine alone. The NASOX regimen is a modified mFOLFIRINOX regimen, which uses irinotecan hydrochloride liposomes (nal-IRI) instead of irinotecan and oral fluoropyrimidine tegafur instead of fluorouracil, and has demonstrated a favorable safety profile... NASOX regimen demonstrated the anticipated efficacy and safety profile in the adjuvant treatment of PDAC following surgery, warranting further investigation."

Clinical • P2 data • Neutropenia • Oncology • Pancreatic Ductal Adenocarcinoma

NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (NAPOLI 3): a randomised, open-label, phase 3 trial. (PubMed, Lancet) - P3 | "Our findings support use of the NALIRIFOX regimen as a possible reference regimen for first-line treatment of mPDAC."

Journal • Metastases • P3 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

Neoadjuvant Radiotherapy Combined With NALIRIFOX and Adebrelimab in pMMR/MSS Locally Advanced Rectal Cancer: A Prospective, Randomized, Phase II Clinical Trial (clinicaltrials.gov) - P2 | N=84 | Recruiting | Sponsor: Sun Yat-sen University | Not yet recruiting ➔ Recruiting

Enrollment open • pMMR • Colorectal Cancer • Oncology • Rectal Adenocarcinoma • Rectal Cancer • Solid Tumor

Nanoliposomal irinotecan (nal-IRI) combined with fruquintinib as Second-line Treatment For Advanced Gastric Cancer : a Single-arm, Open-label, Dose-escalation and Expansion Phase I/II Trial (ESMO 2026) - No abstract available

Clinical • Metastases • P1/2 data • Gastric Cancer • Oncology • Solid Tumor

Nal-IRI and 5-FU/LV compared to 5-FU/LV in patients with cholangio- and gallbladder carcinoma previously treated with gemcitabine-based therapies (NALIRICC – AIO-HEP-0116) (ESMO 2022) - P2 | "The aim of this study was to evaluate the efficacy of pegylated liposomal irinotecan formulation (nal-IRI)/5-FU/leucovorin (LV) compared to 5-FU/LV in 2 nd line BTC...The addition of nal-IRI to 5-FU/LV did not improve PFS or OS compared to 5-FU/LV alone and was associated with higher toxicity. 5FU/LV may be considered as a reasonable alternative in 2 nd line advanced BTC."

Clinical • Gallbladder Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

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

RESILIENT Part 2: A Randomized, Open-Label Phase III Study of Liposomal Irinotecan Versus Topotecan in Adults With Relapsed Small Cell Lung Cancer. (PubMed, J Clin Oncol) - "Liposomal irinotecan and topotecan demonstrated similar median OS and PFS in patients with relapsed SCLC. Although the primary end point of OS was not met, liposomal irinotecan demonstrated a higher ORR than topotecan. The safety profile of liposomal irinotecan was consistent with its known safety profile; no new safety concerns emerged."

Journal • P3 data • Hematological Disorders • Leukopenia • Lung Cancer • Neutropenia • Oncology • Small Cell Lung Cancer • Solid Tumor

NAPOLI-3: A randomized, open-label phase 3 study of liposomal irinotecan + 5-fluorouracil/leucovorin + oxaliplatin (NALIRIFOX) versus nab-paclitaxel + gemcitabine in treatment-naïve patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). (ASCO-GI 2023) - P2, P3 | "First-line NALIRIFOX demonstrated clinically meaningful and statistically significant improvement in OS and PFS compared with Gem+NabP in treatment-naïve patients with mPDAC. The safety profile of NALIRIFOX was manageable and consistent with the profiles of the treatment components. Funding: Funded by Ipsen."

Clinical • Late-breaking abstract • Metastases • P3 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

Integrated nal-IRI/5-FU/LV, benmelstobart, and anlotinib with or without SBRT for second-line metastatic pancreatic cancer: A phase II dual-cohort study (ESMO 2026) - No abstract available

Clinical • Metastases • P2 data • Oncology • Pancreatic Cancer • Solid Tumor

Trial in progress: RASolute 302—A phase 3, multicenter, global, open-label, randomized study of daraxonrasib (RMC-6236), a RAS(ON) multi-selective inhibitor, versus standard of care chemotherapy in patients with previously treated metastatic pancreatic ductal adenocarcinoma (PDAC). (ASCO 2025) - P1, P3 | "Eligibility includes patients ≥18 years old, ECOG performance status 0 or 1, disease progression on 1 prior line of either a 5-fluorouracil or gemcitabine-based regimen in the metastatic setting, and documented RAS mutation status (mutant or wild-type)...A 1:1 randomization of approximately 460 patients will receive daraxonrasib 300 mg daily or investigator's choice of chemotherapy (gemcitabine/nab-paclitaxel, mFOLFIRINOX, nal-IRI/5-FU/LV, or FOLFOX) until unacceptable toxicity or disease progression...Key secondary endpoints include PFS, OS, objective response and quality of life measures in the all-patient population with tumors carrying RAS mutations (G12X, G13X or Q61X) or RAS wild-type. Enrollment for the trial commenced in October 2024."

Clinical • Metastases • P3 data • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • HRAS • KRAS • NRAS

The GIANT trial (ECOG-ACRIN EA2186) methods paper: A randomized phase II study of gemcitabine and nab-paclitaxel compared with 5-fluorouracil, leucovorin, and liposomal irinotecan in older patients with treatment-naïve metastatic pancreatic cancer - defining a new treatment option for older vulnerable patients. (PubMed, J Geriatr Oncol) - P2 | "The GIANT study is the first randomized, prospective national trial evaluating vulnerable OA with mPCA aimed at developing a tailored treatment approach for this patient population. This trial has the potential to establish a new way of objectively selecting vulnerable OA with mPCA for modified treatment and to establish a new standard of care in this growing patient population."

Journal • Metastases • P2 data • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Sarcopenia • Solid Tumor • IL6

NALIRIFOX (iposomal irinotecan + 5-fluorouracil/feucovorin + oxaliplatin) versus FOLFOX [5-fluorouracil/leucovorin + oxaliplatin] as first-line treatment of metastatic pancreatic ductal adenocarcinoma (mPDAC): Real-world comparative overall survival (ESMO-GI 2023) - P3 | "Funding: Ipsen.Background: NAPOLI 3 (NCT04083235), a randomized, open-label, phase 3 study, has demonstrated statistically significant survival results of NALIRIFOX regimen compared with nab-paclitaxel + gemcitabine as first-line (1L) therapy in patients with mPDAC... NALIRIFOX regimen in NAPOLI 3 resulted in significantly improved OS compared to FOLFOX in a RW clinical practice setting, suggesting a clinically meaningful survival benefit associated with liposomal irinotecan in the NALIRIFOX regimen. Limitations of this study include small sample size in the RW FOLFOX cohort and unmeasured confounding."

Clinical • Metastases • Real-world • Real-world evidence • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

A Study of NALIRIFOX in Combination With Radiation Therapy in People With Pancreatic Ductal Adenocarcinoma (PDAC) (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: May 2027 ➔ Sep 2026 | Trial primary completion date: May 2027 ➔ Sep 2026

Trial completion date • Trial primary completion date • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

Clinical Study of Radiotherapy Combined With Adebrelimab and NALIRIFOX for Conversion Therapy in Locally Advanced Pancreatic Cancer (clinicaltrials.gov) - P2 | N=36 | Not yet recruiting | Sponsor: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

New P2 trial • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Phenomenal: Efficacy and safety of liposomal irinotecan in patients with HER2-negative breast cancer and brain metastases (SABCS 2024) - P2 | "Although the primary endpoint was achieved, nal-IRI showed limited antitumor activity in HER2[-] breast cancer pts with progressive BMs. These results do not support further evaluation of this treatment in this patient population."

Clinical • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

NET-02: a randomised, non-comparative, phase II trial of nal-IRI/5-FU or docetaxel as second-line therapy in patients with progressive poorly differentiated extra-pulmonary neuroendocrine carcinoma. (PubMed, EClinicalMedicine) - P2 | "A recognised first-line (1L) treatment for advanced disease is etoposide/platinum-based chemotherapy with no standard second-line (2L) treatment. Patients with histologically-confirmed PD-EP-NEC (Ki-67 > 20%; Grade 3) received IV liposomal irinotecan (nal-IRI) (70 mg/m free base)/5-FU (2400 mg/m)/folinic acid, Q14 days (ARM A), or IV docetaxel (75 mg/m), Q21 days (ARM B), as 2L therapy...This study provides prospective efficacy, toxicity and QoL data in the 2L setting in a disease group of unmet need, and represents some of the strongest evidence available to recommend systemic treatment to these patients. Servier."

Biomarker • Journal • P2 data • Review • Endocrine Cancer • Gastrointestinal Disorder • Neuroendocrine Tumor • Oncology • Solid Tumor

A Prospective Study of Liposomal Irinotecan and Cisplatin Chemotherapy Plus Sequential Radiotherapy for Extensive-Stage Small Cell Lung Cancer (IASLC-WCLC 2026) - P=N/A | "Conclusions : This study suggested that nal-IRI plus cisplatin chemotherapy with sequential consolidative radiotherapy is a promising strategy for ES-SCLC, especially in first-line treatment. A favorable response, prolonged survival, and manageable toxicity warrant further investigation in larger randomized trials."

Clinical • Lung Cancer • Neutropenia • Oncology • Small Cell Lung Cancer • Solid Tumor • Thrombocytopenia

NAPOLI 3, a phase 3 study of NALIRIFOX in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC): Final overall survival (OS) analysis and characteristics of the long-term survivors. (ASCO 2025) - P3 | "The aim of this analysis was to describe long-term survivors among the North American population treated with liposomal irinotecan plus 5-fluorouracil/leucovorin and oxaliplatin (NALIRIFOX) in the NAPOLI 3 trial and to explore clinical and pathological factors that might be associated with prolonged survival... This post hoc analysis investigated characteristics and dosing patterns of long-term survivors from NAPOLI 3 treated with NALIRIFOX in North America. Patients with prolonged OS were generally younger (vs typical mPDAC diagnosis), few had tumors in the head or tail of the pancreas and, overall, CA19-9 levels and ECOG PS were low. A large proportion of long-term survivors experienced liposomal irinotecan and/or oxaliplatin dose reductions or treatment delays, but had prolonged exposure and high cumulative doses of both drugs."

Clinical • Late-breaking abstract • Metastases • P3 data • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • 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

Nanoliposomal Irinotecan With Fluorouracil and Leucovorin or Gemcitabine Plus Cisplatin in Advanced Cholangiocarcinoma: A Phase II Study of the AIO Hepatobiliary-YMO Cancer Groups (NIFE-AIO-YMO HEP-0315). (PubMed, J Clin Oncol) - "Treatment of advanced CCA with nal-IRI/FU/LV demonstrated efficacy in first-line therapy without new safety findings and merits further validation."

Journal • Metastases • P2 data • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Hematological Disorders • Oncology • Solid Tumor

A Study of NALIRIFOX in Combination With Radiation Therapy in People With Pancreatic Ductal Adenocarcinoma (PDAC) (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: Sep 2026 ➔ Sep 2027 | Trial primary completion date: Sep 2026 ➔ Sep 2027

Trial completion date • Trial primary completion date • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

Sequential alternation of nal-IRI/5-FU and gemcitabine/nab-paclitaxel versus nal-IRI/5-FU versus gemcitabine/nab-paclitaxel in first-line metastatic pancreatic cancer: results of the randomized phase II PRODIGE 61-FUNGEMAX trial (France). (PubMed, EClinicalMedicine) - P2 | "Between November 2018 and January 2024, chemotherapy-naive patients aged 18-75 years with histologically confirmed metastatic pancreatic ductal adenocarcinoma (mPDAC) and Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1 were randomly assigned (1:1:1) to receive either nal-IRI (nanoliposomal irinotecan; 70 mg/m2 intravenously [IV] over 90 min) plus leucovorin (400 mg/m2 IV over 30 min) and 5-fluorouracil (5-FU; 2400 mg/m2 IV over 46 h) every 2 weeks (NAPOLI regimen), gemcitabine (1000 mg/m2 IV over 30 min) plus nab-paclitaxel (125 mg/m2 IV over 30 min) on days 1, 8, and 15 of a 28-day cycle (MPACT regimen), or both regimens alternating every 2 months (sequential arm). Future trials should be adequately powered, integrate predictive biomarkers, and include contemporary first-line standards as comparators. This trial was sponsored by the Fédération Francophone de Cancérologie Digestive (FFCD) and supported by a grant from Servier, France."

Journal • P2 data • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Sintilimab Plus NALIRIFOX or Gemcitabine-Cisplatin as First-Line Treatment for Metastatic Biliary Tract Cancer (clinicaltrials.gov) - P2 | N=54 | Recruiting | Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

New P2 trial • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Gallbladder Cancer • Oncology • Solid Tumor