Novartis Investigative Site 79106 Freiburg (Baden-Württemberg) GermanyRekrutierend» Google-MapsNovartis Investigative Site 89081 Ulm (Baden-Württemberg) GermanyRekrutierend» Google-MapsMassachusetts General Hospital . 02114 Boston United StatesRekrutierend» Google-Maps Ansprechpartner: Aaron Paul Doss E-Mail: APAULDOSS@mgh.harvard.edu» Ansprechpartner anzeigen
Dana Farber Cancer Institute Dept.of DFCI 02215 Boston United StatesRekrutierend» Google-Maps Ansprechpartner: Brian Schwalm E-Mail: brian_schwalm@dfci.harvard.edu» Ansprechpartner anzeigenNYU School of Medicine Langone Health 10015 New York United StatesRekrutierend» Google-Maps Ansprechpartner: Sasha Richardson Phone: 212-731-5662 E-Mail: sasha.richardson@nyulangone.org» Ansprechpartner anzeigenNovartis Investigative Site 3000 Leuven BelgiumRekrutierend» Google-MapsNovartis Investigative Site 33076 Bordeaux FranceRekrutierend» Google-MapsNovartis Investigative Site 69373 Lyon FranceRekrutierend» Google-MapsNovartis Investigative Site 20162 Milano ItalyRekrutierend» Google-MapsNovartis Investigative Site 03080 Seoul Korea, Republic ofRekrutierend» Google-MapsNovartis Investigative Site 168583 Singapore SingaporeRekrutierend» Google-MapsNovartis Investigative Site 08036 Barcelona SpainRekrutierend» Google-MapsNovartis Investigative Site 28034 Madrid SpainRekrutierend» Google-MapsNovartis Investigative Site 28050 Madrid SpainRekrutierend» Google-Maps
1. Dose escalation: Incidence and severity of dose limiting toxicities (DLTs) of each combination treatment. (Time Frame - 28 days): A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value that is not primarily related to disease, disease progression, intercurrent illness/injury, or concomitant medications that occurs within the first 28 days of study treatment and meets a defined criteria.
2. Dose escalation: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) by treatment (Time Frame - 24 months): All information obtained on AE will be displayed by treatment group. Summary tables will include only AEs that started/worsened during the cycles of treatment (treatment-emergent AEs).
3. Dose escalation: Frequency of dose interruptions and reductions, by treatment (Time Frame - 24 months): The number of patients with dose adjustments (reductions and interruptions) will be summarized by treatment group.
4. Dose Escalation: Dose intensity by treatment (Time Frame - 24 months): Dose intensity is defined as the ratio of actual cumulative dose received and actual duration of response.
5. PhaseII: Overall Response Rate by Blinded Independent Review Committee (BIRC) per RECIST 1.1 (Time Frame - 24 months): ORR is the proportion of patients with a best overall response (BOR) of Complete Response (CR) or Partial Response (PR).
Secondary outcome:
1. Dose escalation and Phase II: ORR by local review per RECIST 1.1 (Time Frame - 24 months): ORR is the proportion of patients with a BOR of CR or PR.
2. Dose escalation and Phase II: Disease Control Rate (DCR) by local review per RECIST 1.1 (Time Frame - 24 months): DCR is the proportion of patients with a BOR of CR or PR or Stable Disease (SD). The objective of this endpoint is to summarize patients with signs of "activity" defined as either shrinkage of tumor (regardless of duration) or slowing down of tumor growth.
3. Dose escalation and Phase II: Duration of Response (DoR) by local review per RECIST 1.1 (Time Frame - 24 months): Duration of response is defined as the time from the date of the first documented response (CR or PR), to the date of first documented progression, or death due any cause.
4. Dose escalation and Phase II: Progression-Free Survival (PFS) by local review per RECIST 1.1 (Time Frame - 24 months): PFS is defined as the time from the date of start of treatment to the date of the first documented progression, or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment.
5. Phase II: DCR by BIRC per RECIST 1.1 (Time Frame - 24 months): DCR is the proportion of patients with a BOR of CR or PR or SD. The objective of this endpoint is to summarize patients with signs of "activity" defined as either shrinkage of tumor (regardless of duration) or slowing down of tumor growth.
6. Phase II: DoR by BIRC per RECIST 1.1 (Time Frame - 24 months): Duration of response is defined as the time from the date of the first documented response (CR or PR), to the date of first documented progression, or death due any cause.
7. Phase II: PFS by BIRC per RECIST 1.1 (Time Frame - 24 months): PFS is defined as the time from the date of start of treatment to the date of the first documented progression, or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment.
8. Phase II: Overall survival (OS) (Time Frame - 24 months): OS is defined as the time from date of randomization/start of treatment to date of death due to any cause. If a patient is not known to have died, survival will be censored at the date of last known date patient alive.
9. Dose escalation and Phase II: PK parameters - Maximum Concentration (Cmax), as applicable per arm (Time Frame - 5 months): The maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration (mass x volume-1)
10. Dose escalation and Phase II: PK parameters - Minimum Concentration (Cmin), as applicable per arm (Time Frame - 5 months): Observed concentration at the end of a dosing interval (taken directly before next administration)
11. Dose escalation: Time to achieve Cmax - Tmax, as applicable per arm (Time Frame - 5 months): The time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration (time)
12. Dose escalation and Phase II: Plasma or serum concentration vs time profiles - AUCtau, as applicable per arm (Time Frame - 5 months): The Area under curve calculated to the end of a dosing interval (tau) at steady-state (amount x time x volume-1)
13. Dose escalation and Phase II: Plasma or serum concentration vs time profiles - AUCinf, as applicable per arm (Time Frame - 5 months): The AUC from time zero to infinity (mass x time x volume-1)
14. Phase II: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) by treatment (Time Frame - 24 months): All information obtained on AE will be displayed by treatment group. Summary tables will include only AEs that started/worsened during the cycles of treatment (treatment-emergent AEs).
15. Phase II: Frequency of dose interruptions and reductions, by treatment (Time Frame - 24 months): The number of patients with dose adjustments (reductions and interruptions) will be summarized by treatment group.
16. Phase II: Dose intensity by treatment (Time Frame - 24 months): Dose intensity is defined as the ratio of actual cumulative dose received and actual duration of response.
