Neoplasms

All Conditions

Digestive System Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma

Colorectal Neoplasms

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

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Digestive System Neoplasms

Gastrointestinal Diseases

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Antineoplastic Agents

All Drugs and Chemicals

Cetuximab

Trametinib

Antineoplastic Agents, Immunological

Protein Kinase Inhibitors

Enzyme Inhibitors

JDQ443

trametinib

Ribociclib

cetuximab

Novartis Pharmaceuticals

Aaron Paul Doss

Rebecca Heist

Brian Schwalm

Jia Luo

Sasha Richardson

Janice Mehnert

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.

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

KontRASt-03: A Phase Ib/II, Multicenter, Open-label Platform Study of JDQ443 With Select Combinations in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation

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.

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).

The number of patients with dose adjustments (reductions and interruptions) will be summarized by treatment group.

Dose intensity is defined as the ratio of actual cumulative dose received and actual duration of response.

ORR is the proportion of patients with a best overall response (BOR) of Complete Response (CR) or Partial Response (PR).

ORR is the proportion of patients with a BOR of CR or PR.

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.

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.

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.

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.

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.

The maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration (mass x volume-1)

Observed concentration at the end of a dosing interval (taken directly before next administration)

The time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration (time)

The Area under curve calculated to the end of a dosing interval (tau) at steady-state (amount x time x volume-1)

The AUC from time zero to infinity (mass x time x volume-1)

Symptoms and General Pathology

Neoplasm Metastasis

Antibodies

Tislelizumab

Immunoglobulins

JDQ443 in combination with TNO155 and tislelizumab

TNO155

tislelizumab

Obi Okafor

Conor E. Steuer

Teresa Song

Rachel Sanborn

Lorenzo Sellitto

Timothy Burns

Shari A Daniels

Marcelo Vailati Negrao

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.

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

A Phase Ib/II Open-label, Multi-center Dose Escalation Study of JDQ443 in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation

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

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

Tolerability of study drug will be assessed by summarizing the number of and reason for dose delays and dose reductions.

Dose intensity is defined as the ratio of actual cumulative dose received and actual duration of treatment.

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.

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.

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.

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.

Dose intensity is defined as the ratio of actual cumulative dose received and actual duration of treatment. Applies to JDQ443 dose randomization group only

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

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)

BOR is defined as the best overall confirmed response recorded from the start of the treatment until disease progression/recurrence.

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

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.

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

AUC is defined as area under the plasma or serum concentration versus time curve after a dose of JDQ443, TNO155 and tislelizumab

Cmax is defined as the maximum observed plasma or serum drug concentration after single dose administration.

Tmax is defined as the time to reach maximum plasma or serum drug concentration after single dose administration.

To evaluate the immunogenicity of tislelizumab when dosed in combination with JDQ443 and/or TNO155 - only applicable to Arms C and D

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.

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.

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.

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Platform Study of JDQ443 in Combinations in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation	NCT05358249	KRAS G12C Mutan... Carcinoma, Non-... Carcinoma, Non-... Non-Small Cell ... Non-Small Cell ... Nonsmall Cell L... Colorectal Canc... Colorectal Carc... Colorectal Neop... Colorectal Tumo... Neoplasms, Colo...	JDQ443 trametinib Ribociclib cetuximab	18 Years -	Novartis
Platform Study of JDQ443 in Combinations in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation	NCT05358249	KRAS G12C Mutan... Carcinoma, Non-... Carcinoma, Non-... Non-Small Cell ... Non-Small Cell ... Nonsmall Cell L... Colorectal Canc... Colorectal Carc... Colorectal Neop... Colorectal Tumo... Neoplasms, Colo...	JDQ443 trametinib Ribociclib cetuximab	18 Years -	Novartis
Study of JDQ443 in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation	NCT04699188	KRAS G12C Mutan... Carcinoma, Non-... Carcinoma, Colo... Cancer of Lung Cancer of the L... Lung Cancer Neoplasms, Lung Neoplasms, Pulm... Pulmonary Cance... Pulmonary Neopl...	JDQ443 TNO155 tislelizumab	18 Years -	Novartis

Spots Global Cancer Trial Database for kras g12c mutant solid tumors