1. For Phase 1: DLT (Time Frame - For Cohort 1 and Cohort 2 from Day 1 to Day 28 of the maintenance cycle; for Cohort 3, 4 and 5 from Day 1 to Day 42 of the chemoradiotherapy.): Occurrence of dose limiting toxicity (DLT) assessed by frequency and grade of adverse events (AE) according to CTCAE v.5.0.
2. For Phase 2: Overall Survival (Time Frame - From beginning of treatment to 52 weeks): Overall survival (OS) rate
Secondary outcome:
1. PFS (Time Frame - From the date of enrollment to the date of progression or death for any cause, whichever came first, assessed up to 58 weeks): Progression Free Survival (PFS) will be assessed for all enrolled subjects.
2. ORR in CR (Time Frame - At week 10, at week 22, at week 34, at week 46 and at week 58): Objective Response Rate (ORR): ORR is defined as the rate of patients with complete response (CR) (defined according to iRANO criteria)
3. ORR in PR (Time Frame - At week 10, at week 22, at week 34, at week 46 and at week 58): Objective Response Rate (ORR): ORR is defined as the rate of patients with partial response (PR) (defined according to iRANO criteria)
4. DCR in CR (Time Frame - At week 10, at week 22, at week 34, at week 46 and at week 58): Disease Control Rate (DCR) is defined as the rate of patients with complete response (CR) (defined according to iRANO criteria)
5. DCR in PR (Time Frame - At week 10, at week 22, at week 34, at week 46 and at week 58): Disease Control Rate (DCR) is defined as the rate of patients with partial response (PR) (defined according to iRANO criteria)
6. DCR in SD (Time Frame - At week 10, at week 22, at week 34, at week 46 and at week 58): Disease Control Rate (DCR) is defined as the rate of patients with stable disease (SD) (defined according to iRANO criteria)
7. BORR in CR (Time Frame - From date of enrollment to week 58): Considering the best observed response for any subject, Best Overall Response Rate (BORR) is defined as the rate of complete response (CR) (defined according to iRANO criteria)
8. BORR in PR (Time Frame - From date of enrollment to week 58): Considering the best observed response for any subject, Best Overall Response Rate (BORR) is defined as the rate of partial response (PR) (defined according to iRANO criteria)
9. BORR in SD (Time Frame - From date of enrollment to week 58): BConsidering the best observed response for any subject, Best Overall Response Rate (BORR) is defined as the rate of stable disease (SD) (defined according to iRANO criteria)
10. Safety (AE) (Time Frame - Throughout study completion for each patient, a maximum of 58 weeks for each patient): Safety of administration of L19TNF, through an assessed by Common Toxicity Criteria (version 5.0, CTCAE)
11. Safety (SAE) (Time Frame - Throughout study completion for each patient, a maximum of 58 weeks for each patient): Safety of administration of L19TNF, assessed by Common Toxicity Criteria (version 5.0, CTCAE)
12. Safety (DILI) (Time Frame - Throughout study completion for each patient, a maximum of 58 weeks for each patient): Evaluation of possible Drug Induce Liver Injury, caused by L19TNF, assessed by Common Toxicity Criteria (version 5.0, CTCAE)
Experimental: Phase 1 part: Dose Finding Patients will be treated in cohorts according to a 3+3 study design with standard treatment (consisting of radiotherapy of 60 Gy/30 fractions for 6 weeks plus 75 mg/m2 TMZ (temozolomide) daily (chemoradiotherapy), followed by 4 weeks of treatment break, followed by maintenance treatment with 6 maintenance cycles of TMZ 150-200 mg/m2 on Days 1 to 5 q28) combined with L19TNF at different dose levels on Day 1, 3, 5, 22, 24 and 26 of chemoradiotherapy and on Day 1, 3 and 5 of each 28-day chemotherapy maintenance cycle.
Experimental: Phase 2 part: Signal Seeking 32 patients will receive standard chemoradiotherapy and L19TNF at RD and with the administration scheme established in phase I part of the study.
Active Comparator: Phase 2b part: Activity Evaluation_control arm Patients will be randomized 1:1 and treated with either standard chemoradiotherapy and L19TNF as established in phase I part and the phase II part of this study or only chemoradiotherapy (control).
- Arm 2: Patients will receive radiotherapy and TMZ (temozolomide).
Experimental: Phase IIb part: Activity Evaluation_treatment arm Patients will be randomized 1:1 and treated with either standard chemoradiotherapy and L19TNF as established in phase I part and the phase II part of this study or only chemoradiotherapy (control).
- Arm 1: Patients will receive radiotherapy, TMZ (temozolomide) and L19TNF.
Onfekafusp alfa (L19TNF): This is an open label phase 1/2/2b study in subjects with newly diagnosed glioblastoma.
The study will be conducted in three consecutive parts: First the dose finding part to determine the RD of L19TNF in combination with chemoradiotherapy, followed by a signal seeking part that investigates first signs of activity and then an activity evaluation part that studies the efficacy of L19TNF in combination with chemoradiotherapy against chemoradiotherapy alone.
Temozolomide (TMZ): Patients will receive radiotherapy and TMZ. Treatment start with chemoradiotherapy is foreseen after surgical resection or biopsy of glioblastoma
Quelle: ClinicalTrials.gov
Sie können folgenden Inhalt einem Kollegen empfehlen:
"Safety and Efficacy of L19TNF Plus Temozolomide Chemoradiotherapy in Patients With Newly Diagnosed Glioblastoma"
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