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

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

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

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

Study on the efficacy and safety of NALIRIFOX in combination with Iparomlimab and Tuvonralimab Injection and SBRT as neoadjuvant therapy for resectable intrahepatic cholangiocarcinoma with high-risk recurrence factors (ChiCTR) - P4 | N=35 | Not yet recruiting | Sponsor: West China Hospital, Sichuan Universit; West China Hospital, Sichuan Universit

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

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

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

ONIVYDE: standard of care in second-line mPDAC (PragueONCO 2026) - No abstract available

Clinical • Oncology

Interim results of a phase II study of fluorouracil (FU), leucovorin (LV), and nanoliposomal irinotecan (nal-IRI) in previously treated advanced biliary tract cancer (NAPOLI-2) (ESMO-GI 2023) - P2 | "The current standard of care for advanced BTC is gemcitabine (GEM), cisplatin, and durvalumab. Although there is no firmly established second-line treatment, regimens such as FOLFOX, XELOX, FOLFIRI, XELIRI, GEM, GEM/nab-paclitaxel, and capecitabine have activity... FU/LV/nal-IRI appears to be an effective and tolerable treatment regimen for patients with previously-treated advanced BTC in a Western population, including 4 pts with PFS of 7 months or longer. Correlative studies evaluating longitudinal circulating tumor DNA analyses using banked blood specimens are planned. Enrollment in stage 2 is ongoing (NCT04005339)."

Metastases • P2 data • Biliary Cancer • Biliary Tract Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

NAPOLI-2: Fluorouracil, Leucovorin, and Nanoliposomal Irinotecan in Biliary Cancer (clinicaltrials.gov) - P2 | N=48 | Active, not recruiting | Sponsor: Georgetown University | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2025 ➔ Dec 2026 | Trial primary completion date: Dec 2025 ➔ Sep 2025

Enrollment closed • Trial completion date • Trial primary completion date • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Gallbladder Cancer • Oncology • Solid Tumor • CA 19-9 • CD4

Nanoliposomal irinotecan with fluorouracil and folinic acid in patients with unresectable or recurrent pancreatic cancer: a multicenter observational study (NAPOLEON-2). (PubMed, ESMO Gastrointest Oncol) - "Nanoliposomal irinotecan with fluorouracil and folinic acid (NFF) is a standard second- or later-line regimen after gemcitabine-based therapy for patients with unresectable or recurrent pancreatic cancer (urPC). Integrated analysis of the prospective and retrospective phases of the study showed that median OS was 8.0 months. NFF has an appropriate efficacy and safety profile and is a candidate for second- or later-line therapy for urPC."

Journal • Observational data • Anorexia • Neutropenia • Pancreatic Cancer • Solid Tumor

Third-line platinum-based chemotherapy for patients with metastatic pancreatic ductal adenocarcinoma. (PubMed, J Formos Med Assoc) - "This study showed that a platinum-based third-line chemotherapy regimen for patients with metastatic PDAC did not confer a significant survival advantage over non-platinum-based regimens. Platinum-based regimens are associated with modestly increased treatment-related toxicities, thus potentially limiting their tolerability in these heavily pretreated patients."

Journal • 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

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

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

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

Final results from the NIFTY trial, a phase IIb, randomized, open-label study of liposomal Irinotecan (nal-IRI) plus fluorouracil (5-FU)/leucovorin (LV) in patients (pts) with previously treated metastatic biliary tract cancer (BTC) (ESMO 2022) - P2 | "In multivariate analyses for prognostic factors, bone mets was associated with poor PFS; male, CA 19-9 > median, elevated CRP, and albumin > median were associated with poor OS; prior GemCis duration > median was associated with better OS. Conclusions The survival benefits of 2 nd line nal-IRI plus 5-FU/LV versus 5-FU/LV were maintained over an extended follow-up in BTC pts."

Clinical • P2b data • Biliary Cancer • Biliary Tract Cancer • Gastrointestinal Cancer • Oncology • 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

Treatment With Liposomal Irinotecan Plus Fluorouracil and Leucovorin for Patients With Previously Treated Metastatic Biliary Tract Cancer: The Phase 2b NIFTY Randomized Clinical Trial. (PubMed, JAMA Oncol) - P2 | "Patients with advanced BTC whose disease progressed while receiving first-line gemcitabine plus cisplatin with at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors, version 1.1, were eligible. The combination of nal-IRI plus FU/LV could be considered as a second-line treatment option for patients with previously treated advanced BTC. clinicaltrials.gov Identifier: NCT03524508."

Clinical • Journal • Metastases • P2b data • Biliary Cancer • Biliary Tract Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

RESILIENT Part 2: A Randomized, Open-label Phase 3 Study of Liposomal Irinotecan versus Topotecan in Adults with Relapsed Small Cell Lung Cancer (SCLC) (ELCC 2023) - P3 | "Table: 161O Conclusions The primary endpoint of OS for was not met for liposomal irinotecan versus topotecan; however, a doubling of ORR was observed. The safety profile of liposomal irinotecan was consistent with its known safety profile and no new safety concerns emerged."

Clinical • P3 data • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

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

Liposomal irinotecan + 5-fluorouracil/leucovorin + oxaliplatin (NALIRIFOX) versus nab-paclitaxel + gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (mPDAC): 12- and 18-month survival rates from the phase 3 NAPOLI 3 trial. (ASCO 2023) - P2, P3 | "First-line NALIRIFOX demonstrated clinically meaningful and statistically significant improvement in OS and PFS compared with Gem+NabP in patients with mPDAC. The NALIRIFOX safety profile was consistent with the profiles of the regimen components and generally manageable. Clinical trial information: NCT04083235."

Clinical • Metastases • P3 data • Anemia • Gastrointestinal Cancer • Hematological Disorders • Neutropenia • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

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

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

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