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| ID | Type | Description | Link |
|---|---|---|---|
| 2021-006196-42 | EudraCT Number |
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This is Phase Ib/II, multicenter, open-label adaptive platform study of JDQ443 with select therapies in patients with advanced solid tumors harboring the KRAS G12C mutation.
JDQ443 will be considered "backbone" treatment in this trial and combined with selected therapies, or "partner(s)". The combination of a backbone and a partner will constitute a treatment arm. After dose escalation, treatment arms that reach a maximum tolerated dose /recommended dose and are determined to be safe may, but are not required to, proceed to Phase II to further explore safety, tolerability, and anti-tumor activity.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| JDQ443+trametinib | Experimental | JDQ443 in combination with trametinib |
|
| JDQ443+ribociclib | Experimental | JDQ443 in combination with ribociclib |
|
| JDQ443+cetuximab | Experimental | JDQ443 in combination with cetuximab |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| JDQ443 | Drug | KRAS G12C inhibitor, oral |
|
| Measure | Description | Time Frame |
|---|---|---|
| Dose escalation: Incidence and severity of dose limiting toxicities (DLTs) of each combination treatment. | 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. | 28 days |
| Dose escalation: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) by treatment | 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). | 24 months |
| Dose escalation: Frequency of dose interruptions and reductions, by treatment | The number of patients with dose adjustments (reductions and interruptions) will be summarized by treatment group. | 24 months |
| Dose Escalation: Dose intensity by treatment | Dose intensity is defined as the ratio of actual cumulative dose received and actual duration of response. | 24 months |
| PhaseII: Overall Response Rate by Blinded Independent Review Committee (BIRC) per RECIST 1.1 | ORR is the proportion of patients with a best overall response (BOR) of Complete Response (CR) or Partial Response (PR). | 24 months |
| Measure | Description | Time Frame |
|---|---|---|
| Dose escalation and Phase II: ORR by local review per RECIST 1.1 | ORR is the proportion of patients with a BOR of CR or PR. | 24 months |
| Dose escalation and Phase II: Disease Control Rate (DCR) by local review per RECIST 1.1 |
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Inclusion Criteria:
Dose Escalation:
- Patients with advanced (metastatic or unresectable) KRAS G12C mutant solid tumors who have received standard of care therapy or are ineligible to receive such therapy.
Phase II:
All patients:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States | ||
| Dana Farber Cancer Institute |
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.
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| trametinib | Drug | MEK inhibitor, oral |
|
|
| Ribociclib | Drug | CDK4/6 inhibitor, oral |
|
|
| cetuximab | Biological | EGFR inhibitor, intravenous |
|
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.
| 24 months |
| Dose escalation and Phase II: Duration of Response (DoR) by local review per RECIST 1.1 | 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. | 24 months |
| Dose escalation and Phase II: Progression-Free Survival (PFS) by local review 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 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. | 24 months |
| Phase II: DCR by BIRC per RECIST 1.1 | 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. | 24 months |
| Phase II: DoR by BIRC per RECIST 1.1 | 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. | 24 months |
| Phase II: PFS by BIRC 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 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. | 24 months |
| Phase II: Overall survival (OS) | 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. | 24 months |
| Dose escalation and Phase II: PK parameters - Maximum Concentration (Cmax), as applicable per arm | The maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration (mass x volume-1) | 5 months |
| Dose escalation and Phase II: PK parameters - Minimum Concentration (Cmin), as applicable per arm | Observed concentration at the end of a dosing interval (taken directly before next administration) | 5 months |
| Dose escalation: Time to achieve Cmax - Tmax, as applicable per arm | The time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration (time) | 5 months |
| Dose escalation and Phase II: Plasma or serum concentration vs time profiles - AUCtau, as applicable per arm | The Area under curve calculated to the end of a dosing interval (tau) at steady-state (amount x time x volume-1) | 5 months |
| Dose escalation and Phase II: Plasma or serum concentration vs time profiles - AUCinf, as applicable per arm | The AUC from time zero to infinity (mass x time x volume-1) | 5 months |
| Phase II: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) by treatment | 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). | 24 months |
| Phase II: Frequency of dose interruptions and reductions, by treatment | The number of patients with dose adjustments (reductions and interruptions) will be summarized by treatment group. | 24 months |
| Phase II: Dose intensity by treatment | Dose intensity is defined as the ratio of actual cumulative dose received and actual duration of response. | 24 months |
| Boston |
| Massachusetts |
| 02215 |
| United States |
| NYU School of Medicine | New York | New York | 10015 | United States |
| Novartis Investigative Site | Leuven | 3000 | Belgium |
| Novartis Investigative Site | Bordeaux | 33076 | France |
| Novartis Investigative Site | Lyon | 69373 | France |
| Novartis Investigative Site | Freiburg im Breisgau | Baden-Wurttemberg | 79106 | Germany |
| Novartis Investigative Site | Milan | MI | 20162 | Italy |
| Novartis Investigative Site | Singapore | 168583 | Singapore |
| Novartis Investigative Site | Seoul | 03080 | South Korea |
| Novartis Investigative Site | Barcelona | 08036 | Spain |
| Novartis Investigative Site | Madrid | 28034 | Spain |
| Novartis Investigative Site | Madrid | 28050 | Spain |
| ID | Term |
|---|---|
| D002289 | Carcinoma, Non-Small-Cell Lung |
| D015179 | Colorectal Neoplasms |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
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| ID | Term |
|---|---|
| C000726658 | JDQ443 |
| C560077 | trametinib |
| C000589651 | ribociclib |
| D000068818 | Cetuximab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
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