臨床研究等提出・公開システム

Phase 1/2 study of Onivyde, nanoliposomal-irinotecan plus S-1
in metastatic or recurrent pancreatic cancer after first-line gemcitabine-based therapy
(Phoenix study)

Phoenix study (Phoenix study)

55

In the phase 1 part full analysis set, the patients had a median age of 72 years (range, 71-79) in dose level 1, 62 (range, 61-64) in dose level 2, and 68 (range, 45-79) in dose level 3; 66.7% had metastatic disease at diagnosis in the dose level 1, 66.7% in the dose level 2, and 50.0% in the dose level 3; 33.3% had an Eastern Cooperative Oncology Group performance status of 1 in dose level 1, 0% in dose level 2, 50.0% in dose level 2. In the phase 2 part full analysis set, the patients had a median age of 71 years; 75.7% had metastatic disease at diagnosis, 57.1% had an Eastern Cooperative Oncology Group performance status of 1, and 12.2% had UGT1A1 *6/*28 variants.

Of a total of 57 patients enrolled in the study, two were regarded as post facto ineligible (1, adenosquamous carcinoma: 1, non-compliance with eligibility criteria). In the phase 1 part, 12 patients were enrolled at three dose levels: three patients received dose level 1 (nal-IRI, 60 mg/m2; S-1, 60-100 mg/day), three received dose level 2 (nal-IRI, 60 mg/m2; S-1, 80-120 mg/day), and six received dose level 3 (nal-IRI, 70 mg/m2; S-1, 80-120 mg/day). The phase 2 part was initiated after the RP2D was determined, and 43 patients were enrolled. In total, 49 of the 55 patients enrolled in the study received the RP2D, six during the phase 1 part and 43 during the phase 2 part. In total, 49 of the 55 patients enrolled in the study received the RP2D, six during the phase 1 part and 43 during the phase 2 part. Patients were enrolled from May 14, 2021, to November 29, 2022; the data cut-off date was February 15, 2024.

Of the 12 patients enrolled in the phase 1 part, DLT was observed in one patient at dose level 3 (grade 3, anorexia). The frequency of DLT was 8.3% (95% CI, 0.2-38.5). In phase 1 part, 5 of 12 patients (41.7%) had grade 3-4 treatment-emergent AEs. Treatment-related AEs that led to dose reduction of nal-IRI were observed in 4 patients (1 in dose level 1 and 3 in dose level 3) and S-1 in 2 patients (1 in dose level 1 and 1 in dose level 3). There were no treatment-related AEs leading to study drug discontinuation or death during study treatment. In phase 2 part, 35 of 49 patients (71.4%) who received the RP2D experienced grade 3-4 treatment-emergent AEs. Serious AEs were reported for 22 patients (44.9%) and were considered treatment-related in 10 patients (20.4%). Among 49 patients who received the RP2D, the most common treatment-emergent AEs were hypoalbuminemia (98.0%), anemia (98.0%), and anorexia (81.6%). The most common grade 3-4 treatment-emergent AEs were hypokalemia (30.6%), neutrophil count decreased (22.4%), and anorexia (20.4%).

Primary endpoint: OS Of the 49 patients in the phase 2 FAS at the data cut-off (February 15, 2024), 42 patients had died. Kaplan-Meier curves showed that the median OS was 10.3 months (95% CI, 8.1-12.0 months), and the 6- and 12-month OS rates were 73.5% (95% CI, 58.7-83.6%) and 36.7% (95% CI, 58.7-83.6%), respectively. Secondary endpoint: PFS Of the 49 patients in the phase 2 FAS at the data cut-off (February 15, 2024), a total of 45 patients progressed or died, and four patients were still on treatment. The median PFS was 5.7 months (95% CI: 4.4-7.3 months), and the 6- and 12-month PFS rates were 42.9% and 20.4%, respectively. Secondary endpoint: ORR Ten of 49 patients who received the RP2D had achieved a confirmed PR, resulting in an ORR of 20.4% (95% CI, 10.2-34.3%).

The data demonstrate that nal-IRI plus S-1 is an effective and well-tolerated treatment regimen for metastatic PC in a second-line setting. Notably, patients treated with nal-IRI plus S-1 reached a median OS of 10.3 months and an ORR of 20.4%. Although preliminary evidence of an antitumor effect of this combination regimen was observed, the present study showed promising results compared with previous studies.

Sept. 30, 2025

Sept. 30, 2025

No

not applicable

https://jrct.mhlw.go.jp/latest-detail/jRCTs031210040

Ikeda Masafumi

National Cancer Center Hospital East

6-5-1,Kashiwanoha,Kashiwa,Chiba 277-8577,Japan

masikeda@east.ncc.go.jp

Imaoka Hiroshi

National Cancer Center Hospital East

6-5-1,Kashiwanoha,Kashiwa,Chiba 277-8577,Japan

+81-4-7133-1111

hiimaoka@east.ncc.go.jp

Complete

April. 01, 2021

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

(1) Histologically or cytologically confirmed adenocarcinoma;
(2) Metastatic or recurrent* pancreatic cancer diagnosed by contrast-enhanced CT(chest,abdomen,and pelvis) and / or MRI(abdomen and pelvis) imaging;
*If the patient received adjuvant chemotherapy and the diasese recurred within 6 manths after the completion,the patient is excluded from this study.
(3) Age of 20-80 years at time of enrollment;
(4) Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
(5) Metastatic of recurrent pancreatic cancer refractory to first-line gemcitabin-based chemotherapy;
(6) Recovery of any toxicities by prior treatment except alopecia to grade 1 or less;
(7) Adequate oral intake;
(8) Adequate hematologic and organ function defined by the following laboratory test results,obtained within 7days prior to study enrollment;
1) Absolute neutrophil count (ANC) >- 1,500/mm3,
2) Hemoglobin >- 9.0g/dL,
3) Platelet count >- 100,000/mm3,
4) Serum total bilirubin <- 2.0mg/dL,
5) Aspartate transaminase (AST) <- 2.5 x upper limit of normal (ULN) without liver metastases (<-5 x ULN is acceptable if liver metastases are present),
6) Alanine transminase (ALT) <-2.5 x ULN without liver metastases (<-5 x ULN is acceptable if liver metastases are present).
7) Serum albmin >-3.0 g/ dL,
8) Creatinine clearance (CCr) >-50mL/min
(9) Signed written informed concsent form

(1) Prior exposure to irinotecan or fluropyrimidine*;
*Ajuvant chemotherapy with irinotecan and/or fluorouracil is permitted.
(2) History of malignancy (except for adequately treated carcinoma in situ, non-invasive cancer) within 2 years prior to study entry except if the patient has undergone potentially curative therapy with no evidence of that disease recurrence for 2 years;
(3) Evidence of uncontrolled,active infection,requiring anti-infectious treatment,except for viral hepatitis;
(4) Any chemotherapy for pancreatic cancer within 14days prior to the initiation of study treatment;
(5) Any major surgery*,radiotherapy, immunotherapy,or investigational drugs within 28 days prior to the initiation of study treatment;*In cases with exploratory laparotomy,intestinal bypass surgery,billiary bypass surgery ,or endoscopic resection, study entry is permitted if 14 days have passed.
(6) Suspected or known central nervous system (CNS) metastases (imaging required only if participants are symptomatic);
(7) Symptomatic ascites or pleural effusion;
(8) Significant lung disease,including interstitial lung disease,pulmonary fibrosis,or severe emphysema;
(9) Active watery diarrhea;
(10) Pregnant, lactating or females of childbearing age unless using highly effective contraception;
(11) Male with partner of child-bearing potential unless using highly effective contraception;
(12) Patients with significant psychiatric disorder;
(13) Significant comorbidities,such as uncontrolled diabetes mellitus, uncontrolled hypertension, New York Heart Association (NYHA) Class III or greater cardiac disease, chronic kidney disease, or liver dysfunction;
(14) Treatment with the following medications:
1) Systemic immunosuppressive medication, including corticosteroids, and immunosuppressant,
2) Flucytosine,
3) Phenytoin,
4) Warfarin,
5) Rifampicin,
6) Atazanavir sulfate,
(15) History of hypersensitivity to the following agents:
1) Irinotecan,
2) Fluoropyrimidines,
3) Any of the components/excipients of nanoliposomal-irinotecan (nal-IRI) and S1, or other liposomal products,
(16) Cannnot stop medications that are potent CYP3A4 inducers within 2 weeks and inhibitors within 1 week before start of study treatment.
(17) Patients whose entry in the study is considered by the investigator to be inappropriate;
(18) History of arterial thromboembolism (e.g., myocardial infarction, unstable angina,and cerebral
infarction) within 6 months prior to the initiation of study treatment,
(19) Presence of a UGT1A1 genetic polymorphism (UGT1A1*6/*6, UGT1A1*28/*28, or UGT1A1*6/*28 ;
phase 1 only)

Both

Metastatic or recurrent pancreatic cancer

Patients continue to receive treatment according to a 14-day cycle unless the dicsontinuation criteria
are met.
Nanoliposomal irinotecan : intravenous infusion of over 90 min.
S-1 : Oral administration twice aday for consecutive 7 days
Phase 1 part:
Nanoliposomal irinotecan, 50~70mg/m2
S-1, 60~120mg/m2
Phase 2 part :
Phase 2 part will be initiated after recommended dose has been determined in Phase 2 part.

Nanoliposomal irinotecan ,Combination chemotherapy

Phase 1 part : frequency of dose-limiting toxicities (DLTs)
Phase 2 part : overall survival

Phase 1 part : frequency of other adverse events
Phase 2 part : objective response rate, progression-free survival,
disease control rate, frequency of adverse events.

+81-4-7133-1111

Feb. 09, 2021

none