Ipsen Announces Results from Phase III RESILIENT Trial Evaluating Onivyde® in Second-Line Monotherapy for Small Cell Lung Cancer
Ipsen announced that its Phase III RESILIENT trial for Onivyde (irinotecan liposomal injection) in small cell lung cancer did not meet the primary endpoint of overall survival compared to topotecan. Although the trial did show a doubling of the objective response rate in favor of Onivyde, it raises concerns for investors regarding efficacy. The safety profile remained consistent with previous studies, causing no new safety issues. Detailed results will be shared at a medical conference, and data will be communicated to regulatory agencies.
- Doubling of the secondary endpoint of objective response rate (ORR) in favor of Onivyde.
- Safety profile consistent with previously reported studies.
- Primary endpoint of overall survival (OS) was not met.
- Concerns raised about the efficacy of Onivyde compared to topotecan.
- At the primary analysis, the trial did not meet its primary endpoint of overall survival (OS)
- The safety profile was consistent with previously reported studies of Onivyde® (irinotecan liposomal injection)
- The clinical study results will be communicated with the regulatory agency
Ipsen (Euronext: IPN; ADR: IPSEY) announced today that the Phase III RESILIENT trial did not meet its primary endpoint of overall survival (OS) compared to topotecan. The trial is evaluating Onivyde® (irinotecan liposomal injection) versus topotecan in patients with small cell lung cancer (SCLC), who have progressed on or after platinum-based first-line therapy treatment. RESILIENT is a Phase III trial conducted in two parts; the first part read out in 2020 confirming the safety, dosing and efficacy of Onivyde; part two is evaluating the efficacy of Onivyde versus topotecan. Detailed results from the RESILIENT trial will be presented at an upcoming medical conference.
The analysis concluded that the primary endpoint OS was not met in patients treated with Onivyde versus topotecan. However, a doubling of the secondary endpoint of objective response rate (ORR) in favor of Onivyde was observed. The safety and tolerability of Onivyde was consistent with its already-known safety profile, and no new safety concerns emerged. The clinical study results will be communicated with the regulatory agency.
Onivyde is currently approved in most major markets including the
ENDS
About RESILIENT
RESILIENT is a randomized, open-label Phase III trial of Onivyde (irinotecan liposome injection) versus topotecan in patients with small cell lung cancer who have progressed on or after platinum-based first-line therapy. The trial is being conducted in two parts:
- Part 1: Open-label dose-finding trial of Onivyde. 30 patients were enrolled.
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Part 1 Primary endpoints:
- Describe the safety and tolerability of Onivyde monotherapy administered every 2 weeks
- Determine the optimal Onivyde monotherapy dose for Part 2 of this trial
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Part 2: A randomized, efficacy study of Onviyde versus intravenous (IV) topotecan. Approximately 450 patients were enrolled in part 2.
Part 2 objectives: To compare overall survival (OS) following treatment with Onivyde with OS following treatment with IV topotecan
The primary outcome measure is OS. Secondary outcome measures include progression-free survival, objective response rate, quality of life assessment using
About Onivyde (irinotecan liposome injection)
Ipsen has exclusive commercialization rights for the current and potential future indications for Onivyde in the
Indication -
Onivyde is approved by the
IMPORTANT SAFETY INFORMATION -
BOXED WARNINGS: SEVERE NEUTROPENIA and SEVERE DIARRHEA
Fatal neutropenic sepsis occurred in Withhold Onivyde for absolute neutrophil count below 1500/mm3 or neutropenic fever. Monitor blood cell counts periodically during treatment.
Severe diarrhea occurred in Grade 2–4 severity. Administer loperamide for late diarrhea of any severity. Administer atropine, if not contraindicated, for early diarrhea of any severity.
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CONTRAINDICATION
Onivyde is contraindicated in patients who have experienced a severe hypersensitivity reaction to Onivyde or irinotecan hydrochloride.
Warnings and precautions
Severe neutropenia: see boxed WARNING. In patients receiving Onivyde/5-FU/LV, the incidence of Grade 3/4 neutropenia was higher among Asian (18/33 [
Severe diarrhea: see boxed WARNING. Severe and life-threatening late-onset (onset >24 hours after chemotherapy [
Interstitial lung disease (ILD): Irinotecan HCl can cause severe and fatal ILD. Withhold Onivyde patients with new or progressive dyspnea, cough, and fever, pending diagnostic evaluation. Discontinue Onivyde in patients with a confirmed diagnosis of ILD
Severe hypersensitivity reactions: Irinotecan HCl can cause severe hypersensitivity reactions, including anaphylactic reactions. Permanently discontinue Onivyde in patients who experience a severe hypersensitivity reaction
Embryo-fetal toxicity: Onivyde can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during and for 1 month after Onivyde treatment
Adverse reactions
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The most common adverse reactions (≥
20% ) were diarrhea (59% ), fatigue/asthenia (56% ), vomiting (52% ), nausea (51% ), decreased appetite (44% ), stomatitis (32% ), and pyrexia (23% ) -
The most common Grade 3/4 adverse reactions (≥
10% ) were diarrhea (13% ), fatigue/asthenia (21% ), and vomiting (11% ) -
Adverse reactions led to permanent discontinuation of Onivyde in
11% of patients receiving Onivyde/5- FU/LV; The most frequent adverse reactions resulting in discontinuation of Onivyde were diarrhea, vomiting, and sepsis -
Dose reductions of Onivyde for adverse reactions occurred in
33% of patients receiving Onivyde/5 FU/LV; the most frequent adverse reactions requiring dose reductions were neutropenia, diarrhea, nausea, and anemia -
Onivyde was withheld or delayed for adverse reactions in
62% of patients receiving Onivyde/5-FU/LV; the most frequent adverse reactions requiring interruption or delays were neutropenia, diarrhea, fatigue, vomiting, and thrombocytopenia -
The most common laboratory abnormalities (≥
20% ) were anemia (97% ), lymphopenia (81% ), neutropenia (52% ), increased ALT (51% ), hypoalbuminemia (43% ), thrombocytopenia (41% ), hypomagnesemia (35% ), hypokalemia (32% ), hypocalcemia (32% ), hypophosphatemia (29% ), and hyponatremia (27% )
Drug Interactions
- Avoid the use of strong CYP3A4 inducers, if possible, and substitute non-enzyme inducing therapies ≥2 weeks prior to initiation of Onivyde
- Avoid the use of strong CYP3A4 or UGT1A1 inhibitors, if possible, and discontinue strong CYP3A4 inhibitors ≥1 week prior to starting therapy
Special Populations
- Pregnancy and Reproductive Potential: See WARNINGS & PRECAUTIONS. Advise males with female partners of reproductive potential to use condoms during and for 4 months after Onivyde treatment
- Lactation: Advise nursing women not to breastfeed during and for 1 month after Onivyde treatment
Please see full
About Ipsen
Ipsen is a global, mid-sized biopharmaceutical company focused on transformative medicines in Oncology, Rare Disease and Neuroscience. With Specialty Care sales of
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