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Lurbinectedin · 5 trials · 9 indications
To evaluate the antitumor activity of Lurbinectedin in terms of overall response rate (ORR), according to RECIST v.1.1, in patients with advanced pancreatic cancer with DNA repair mutations.
Progression Free Survival (PFS) rate is the proportion of participants who have not experienced disease progression (as determined by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1) or death from any cause
The number of incidences of grade 3 or dose-limiting toxicities of the combination of lurbinectedin with osimertinib assessed using NCI CTCAE v5.0 criteria.
Will be defined as having one or none of the following: * Grade 4 or 5 serious adverse events possibly, probably, or definitely related to protocol treatment from 30 days from the start of RT. * Any adverse events possibly, probably, or definitely related to protocol treatment that leads to prolonged dose delays (defined as with-holding of two consecutive doses of lurbinectedin). * Any adverse event possibly, probably, or definitely related to treatment resulting in the permanent discontinuation of lurbinectedin. Will be analyzed separately for safety cohorts 1 and 2 and will be summarized descriptively using frequencies and percentages. These will be compared to rates reported by Trigo et al. from lurbinectedin monotherapy.
| Arm | Type | Description |
|---|---|---|
| Lurbinectedin | EXPERIMENTAL | Lurbinectedin will be administered intravenously (IV) as a 1-hour (±10 min) infusion on Day 1 of each cycle (one cycle = 3 weeks ± 48 hours). |
| Durvalumab and lurbinectedin treatment arm | EXPERIMENTAL | Durvalumab taken in combination with lurbinectedin in participants with ES-SCLC after first line induction therapy with durvalumab and platinum plus etoposide containing regimen. |
| Phase I Does De-Escalation | EXPERIMENTAL | 3.2 mg/m2 or 2.6 mg/m2 dose of lurbinectedin with 80 mg or 40 mg daily dose of osimertinib. This will occur day 1 of each 21 day cycle. |
| Phase II Dose Expansion | EXPERIMENTAL | 3.2 mg/m2 or 2.6 mg/m2 dose of lurbinectedin with 80 mg or 40 mg daily dose of osimertinib. This will occur day 1 of each 21 day cycle. |
| Treatment (lurbinectedin and palliative radiation therapy) | EXPERIMENTAL | Patients undergo palliative RT over 5 or 10 treatment fractions at the discretion of the treating physician daily for 21 days. Patients also receive lurbinectedin IV over 1 hour on day 1 of each cycle. Cycles of lurbinectedin repeat every 21 days in the absence of disease progression or unacceptable toxicity. |
| Phase 1 Part 1: Dose Selection | EXPERIMENTAL | Pediatric participants ≥ 2 to \< 18 years of age with previously treated solid tumors of any histology at 5 dose levels to determine the RP2D, followed by a safety expansion cohort. Participants aged ≥ 6 to \< 18 years will be enrolled at the starting dose of 3.2 mg/m\^2 lurbinectedin. If, after review, the starting dose of 3.2 mg/m\^2 lurbinectedin Q3W is deemed safe in participants aged ≥ 6 to \< 18 years, participants aged ≥ 2 to \< 6 years may enroll and start at the dose as determined by the DMC. After this, the study opens to all participants (aged ≥ 2 to \< 18 years) for all dose levels. Upon completion of the cohort at all dose levels, participants may be eligible to enroll in a safety expansion cohort. |
| Phase 1 Part 2: RP2D | EXPERIMENTAL | Participants aged ≥ 2 to ≤ 30 years with recurrent/refractory Ewing sarcoma at the RP2D to assess safety and efficacy signals. |
| Phase 2 | EXPERIMENTAL | If a signal of efficacy is observed in Phase 1 Part 2, additional participants aged ≥ 2 to ≤ 30 years with recurrent/refractory Ewing sarcoma will be enrolled. Phase 2 will further assess the safety and efficacy of lurbinectedin monotherapy. |
| Name | Type | Description |
|---|---|---|
| Lurbinectedin 4 MG Injection [Zepzelca] | DRUG | Lurbinectedin will be administered with a minimum total volume of 100 mL of solution for infusion (either on 5% glucose or 0.9% sodium chloride). Lurbinectedin will be administered intravenously through peripheral or central lines at a dose of 3.2 mg/m2 at a fixed infusion rate. |
| Lurbinectedin | DRUG | Administered by intravenous (IV) infusion |
| Durvalumab | DRUG | Administered by intravenous (IV) infusion |
| Osimertinib | DRUG | Two osimertinib does of 80 mg or 40 mg orally once daily, as assigned by the dose de-escalation cohort for each 21 day cycle. |
| Palliative Radiation Therapy | RADIATION | Undergo RT |
Inclusion Criteria: * Voluntary written informed consent form (ICF) of the patient obtained before any study-specific procedure. * Age ≥ 18 years of age; male or female. * Eastern Cooperative Oncology Group (ECOG) performance status (PS) score ≤1 * Histologically or cytologically confirmed gastroin...