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JOURNAL ONKOLOGIE – STUDIE
KontRASt-01

Study of JDQ443 in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation

Rekrutierend

NCT-Nummer:
NCT04699188

Studienbeginn:
Februar 2021

Letztes Update:
01.05.2024

Wirkstoff:
JDQ443, TNO155, Tislelizumab

Indikation (Clinical Trials):
Carcinoma, Lung Neoplasms, Neoplasms, Carcinoma, Non-Small-Cell Lung, Colorectal Neoplasms

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
Novartis Pharmaceuticals

Collaborator:
-

Kontakt

Studienlocations
(3 von 44)

Novartis Investigative Site
01307 Dresden
(Sachsen)
GermanyRekrutierend» Google-Maps
Novartis Investigative Site
45147 Essen
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Novartis Investigative Site
79106 Freiburg
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Novartis Investigative Site
50937 Koeln
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Washington Uni School of Med .
63110 Saint Louis
United StatesZurückgezogen» Google-Maps
Uni of TX MD Anderson Cancer Cntr Dept of MD Anderson CancerCent
77030 Houston
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Rebecca Okumah
Phone: +1 713 745 3039
E-Mail: rokumah@mdanderson.org» Ansprechpartner anzeigen
Novartis Investigative Site
3000 Melbourne
AustraliaRekrutierend» Google-Maps
Novartis Investigative Site
H2W 1T8 Montreal
CanadaRekrutierend» Google-Maps
Novartis Investigative Site
DK-2100 Copenhagen
DenmarkRekrutierend» Google-Maps
Novartis Investigative Site
13273 Marseille
FranceRekrutierend» Google-Maps
Novartis Investigative Site
94800 Villejuif
FranceRekrutierend» Google-Maps
Novartis Investigative Site
277 8577 Kashiwa
JapanRekrutierend» Google-Maps
Novartis Investigative Site
241-8515 Yokohama-city
JapanRekrutierend» Google-Maps
Novartis Investigative Site
541-8567 Osaka-city
JapanRekrutierend» Google-Maps
Novartis Investigative Site
104 0045 Chuo ku
JapanRekrutierend» Google-Maps
Novartis Investigative Site
135 8550 Koto ku
JapanRekrutierend» Google-Maps
Novartis Investigative Site
03722 Seoul
Korea, Republic ofRekrutierend» Google-Maps
Novartis Investigative Site
1066 CX Amsterdam
NetherlandsRekrutierend» Google-Maps
Novartis Investigative Site
119074 Singapore
SingaporeRekrutierend» Google-Maps
Novartis Investigative Site
168583 Singapore
SingaporeRekrutierend» Google-Maps
Novartis Investigative Site
08907 Hospitalet de LLobregat
SpainRekrutierend» Google-Maps
Novartis Investigative Site
15706 Santiago De Compostela
SpainRekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

Brief Summary:

This is a phase Ib/II open label study. The escalation part will characterize the safety and

tolerability of JDQ443 single agent and JDQ443 in combination with the other study treatments

(TNO155 and tislelizumab) in advanced solid tumor patients. After the determination of the

maximum tolerated dose / recommended dose for a particular treatment arm, dose expansion will

assess the anti-tumor activity and further assess the safety, tolerability, and PK/PD of each

regimen at the maximum tolerated dose / recommended dose or lower dose.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Adult patients with advanced (metastatic or unresectable) KRAS G12C mutant solid

tumors who have received standard of care or are intolerant or ineligible to approved

therapies

- ECOG Performance Status of 0 or 1

- At least one measurable lesion as defined by RECIST 1.1

- Prior treatment with a KRAS G12C inhibitor may be allowed for dose escalations of

combinations and a subset of groups in dose expansion

Exclusion Criteria:

- Tumors harboring driver mutations that have approved targeted therapies, with the

exception of KRAS G12C mutations

- Symptomatic brain metastases or known leptomeningeal disease. Patients with

asymptomatic treated or untreated brain metastases may be eligible

- Clinically significant cardiac disease or risk factors at screening

- A medical condition that results in increased photosensitivity Other protocol-defined

inclusion/exclusion criteria may apply.

Studien-Rationale

Primary outcome:

1. Dose Escalation: Incidence and severity of dose limiting toxicities (DLTs) during the first cycle of monotherapy or combination treatment (Time Frame - 21 days):
A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle of treatment

2. Dose Escalation: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) (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):
Tolerability of study drug will be assessed by summarizing the number of and reason for dose delays and dose reductions.

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 treatment.

5. Dose Expansion: Overall response rate (ORR) per RECIST v1.1, by treatment (Time Frame - 24 months):
Overall response rate is defined as the proportion of patients with a BOR of CR or PR according to RECIST 1.1, and will be summarized along with the corresponding 95% exact binomial confidence interval (CI). Applies to all groups except the brain metastasis group.

6. Dose expansion: Overall intracranial response rate (OIRR) per mRANO-BM (Time Frame - 24 months):
OIRR per mRANO-BM is defined as the proportion of participants with a best overall intracranial response (BOIR) of CR or PR according to mRANO-BM criteria, and will be summarized along with the corresponding 90% and 95% exact CI. Applies to brain metastasis group only.

7. Dose expansion: Incidence and severity of AEs and SAEs (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). Applies to JDQ443 dose randomization group only.

8. Dose expansion: frequency of dose interruptions and reductions, by treatment (Time Frame - 24 months):
Tolerability of study drug will be assessed by summarizing the number of and reason for dose delays and dose reductions. Applies to JDQ443 dose randomization group only.

9. Dose expansion: Dose intensity by treatment (Time Frame - 24 months):
Dose intensity is defined as the ratio of actual cumulative dose received and actual duration of treatment. Applies to JDQ443 dose randomization group only

10. Dose expansion: ORR per RECIST 1.1 of JDQ443 single agent in patients with non-small cell lung cancer (JDQ443 dose randomization group only) (Time Frame - 24 months):
Overall response rate is defined as the proportion of patients with BOR of CR or PR according to RECIST 1.1, and will be summarized along with the corresponding 95% exact binomial confidence interval (CI). Applies to JDQ443 dose randomization group only

Secondary outcome:

1. Dose Escalation and Expansion: ORR per RECIST v1.1 (Time Frame - 24 months):
Overall response rate is defined as the proportion of patients with a BOR of CR or PR according to RECIST 1.1, and will be summarized along with the corresponding 95% exact binomial confidence interval (CI)

2. Dose Escalation and Expansion: Best Overall Response (BOR) per RECIST v1.1 (Time Frame - 24 months):
BOR is defined as the best overall confirmed response recorded from the start of the treatment until disease progression/recurrence.

3. Dose Escalation and Expansion: Progression-free survival (PFS) per RECIST v1.1, Overall Survival (OS) (Time Frame - 24 months):
Per RECIST 1.1, PFS is defined as the time from the date of start of treatment to the date of the first documented progression, or death. If patient has not had an event, PFS will be censored at the date of last adequate tumor assessment. PFS will be summarized using the Kaplan-Meier method, along with 95% CI

4. Dose Escalation and Expansion: Duration of Response (DOR) per RECIST v1.1 (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. Estimates will use Kaplan-Meier method, and median DOR and corresponding 95% CI will be presented.

5. Dose Escalation and Expansion: Disease Control Rate (DCR) per RECIST v1.1 (Time Frame - 24 months):
The disease control rate is calculated as the percentage of patients with advanced or metastatic cancer who have achieved complete response, partial response and stable disease. It will be summarized along with the corresponding 95% exact CI

6. Dose Escalation and Expansion: Plasma or serum concentration vs time profiles (AUC) by treatment (Time Frame - Up to 24 months):
AUC is defined as area under the plasma or serum concentration versus time curve after a dose of JDQ443, TNO155 and tislelizumab

7. Dose Escalation and Expansion: Plasma concentration (Cmax) by treatment (Time Frame - Up to 24 months):
Cmax is defined as the maximum observed plasma or serum drug concentration after single dose administration.

8. Dose Escalation and Expansion: Time to achieve Cmax (Tmax) by treatment (Time Frame - Up to 24 months):
Tmax is defined as the time to reach maximum plasma or serum drug concentration after single dose administration.

9. Dose Escalation and Expansion: Antidrug antibody (ADA) incidence by treatment (Time Frame - Up to 24 months):
To evaluate the immunogenicity of tislelizumab when dosed in combination with JDQ443 and/or TNO155 - only applicable to Arms C and D

10. Dose Expansion: Dose intensity by treatment (Time Frame - 24 months)

11. Dose Expansion: Frequency of dose interruptions and reductions, by treatment (Time Frame - 24 months):
Tolerability of study drug will be assessed by summarizing the number of and reason for dose delays and dose reductions.

12. Dose Expansion: Incidence and severity of dose limiting toxicities (DLTs) during the first cycle of monotherapy or combination treatment (Time Frame - 21 days):
A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle of treatment

13. Dose Expansion: Incidence and severity of AEs and SAEs by treatment (Time Frame - 24 months)

14. Dose expansion: Intracranial disease control rate (IDCR) per mRANO-BM (Time Frame - 24 months):
IDCR is the proportion of participants with a confirmed BOIR of CR or PR or SD (or non-CR/non-PD) per mRANO-BM criteria. It will be summarized along with the corresponding 90% and 95% CI. Applies to the brain metastasis group only.

15. Dose expansion: Best overall intracranial response (BOIR) per mRANO-BM (Time Frame - 24 months):
BOIR is defined as the best overall confirmed response recorded from the start of the treatment until disease progression/recurrence per mRANO-BM, or until patient comes off study, whichever comes first. BOIR will be summarized along with the corresponding 95% exact CI. Applies to the brain metastasis group only.

16. Dose expansion: Intracranial progression free survival (IPFS) per mRANO-BM (Time Frame - 24 months):
IPFS is defined as the time from the date of start of treatment to the date of the first documented progression per mRANO-BM, or death due to any cause. If a patient has not had an event, IPFS will be censored at the date of last adequate tumor assessment. IPFS will be summarized using the Kaplan-Meier method. Median IPFS and IPFS probability at pre specified time-points will be presented along with 95% CI. Applies to the brain metastasis group only.

17. Dose expansion: Duration of intracranial response (DOIR) per mRANO-BM (Time Frame - 24 months):
DOIR is defined as the time from the date of first documented intracranial response of either CR or PR to the date of the first documented intracranial progression as per mRANO-BM criteria as assessed by central review or date of death due to underlying cause of cancer. DOIR will be summarized using the KM method if data permit. Median DOIR, with corresponding 95% CI. KM estimates for DOIR proportions at specific time points, along with 95% CI will also be provided. Applies to the brain metastasis group only.

Studien-Arme

  • Experimental: Arm A
    JDQ443
  • Experimental: Arm B
    JDQ443 in combination with TNO155
  • Experimental: Arm C
    JDQ443 in combination with tislelizumab
  • Experimental: Arm D
    JDQ443 in combination with TNO155 and tislelizumab

Geprüfte Regime

  • JDQ443:
    KRAS G12C inhibitor
  • TNO155:
    SHP2 inhibitor
  • tislelizumab:
    Anti PD1 antibody

Quelle: ClinicalTrials.gov


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