Clinical trial NCT04699188: Study of JDQ443 in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation
Official title: A Phase Ib/II Open-label, Multi-center Dose Escalation Study of JDQ443 in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: KRAS G12C Mutant Solid Tumors
Carcinoma, Non-Small-Cell Lung
Carcinoma, Colorectal
Cancer of Lung
Cancer of the Lung
Lung Cancer
Neoplasms, Lung
Neoplasms, Pulmonary
Pulmonary Cancer
Pulmonary Neoplasms
Keywords: KRAS
KRAS G12C
Metastatic cancer
Advanced cancer
Enzyme inhibitor
PD-1
SHP2
Targeted therapy
Non-small-cell lung cancer
colorectal cancer
Molecular mechanisms of pharmacological action
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2021-01-07
Enrollment: 344
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Dose Escalation: Incidence and severity of dose limiting toxicities (DLTs) during the first cycle of monotherapy or combination treatment
timeFrame: 21 days
measure: Dose Escalation: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
timeFrame: 24 months
measure: Dose Escalation: Frequency of dose interruptions and reductions, by treatment
timeFrame: 24 months
measure: Dose Escalation: Dose intensity by treatment
timeFrame: 24 months
measure: Dose Expansion: Overall response rate (ORR) per RECIST v1.1, by treatment
timeFrame: 24 months
measure: Dose expansion: Overall intracranial response rate (OIRR) per mRANO-BM
timeFrame: 24 months
measure: Dose expansion: Incidence and severity of AEs and SAEs
timeFrame: 24 months
measure: Dose expansion: frequency of dose interruptions and reductions, by treatment
timeFrame: 24 months
measure: Dose expansion: Dose intensity by treatment
timeFrame: 24 months
measure: Dose expansion: ORR per RECIST 1.1 of JDQ443 single agent in patients with non-small cell lung cancer (JDQ443 dose randomization group only)
timeFrame: 24 months
Secondary outcomes:
measure: Dose Escalation and Expansion: ORR per RECIST v1.1
timeFrame: 24 months
measure: Dose Escalation and Expansion: Best Overall Response (BOR) per RECIST v1.1
timeFrame: 24 months
measure: Dose Escalation and Expansion: Progression-free survival (PFS) per RECIST v1.1, Overall Survival (OS)
timeFrame: 24 months
measure: Dose Escalation and Expansion: Duration of Response (DOR) per RECIST v1.1
timeFrame: 24 months
measure: Dose Escalation and Expansion: Disease Control Rate (DCR) per RECIST v1.1
timeFrame: 24 months
measure: Dose Escalation and Expansion: Plasma or serum concentration vs time profiles (AUC) by treatment
timeFrame: Up to 24 months
measure: Dose Escalation and Expansion: Plasma concentration (Cmax) by treatment
timeFrame: Up to 24 months
measure: Dose Escalation and Expansion: Time to achieve Cmax (Tmax) by treatment
timeFrame: Up to 24 months
measure: Dose Escalation and Expansion: Antidrug antibody (ADA) incidence by treatment
timeFrame: Up to 24 months
measure: Dose Expansion: Dose intensity by treatment
timeFrame: 24 months
measure: Dose Expansion: Frequency of dose interruptions and reductions, by treatment
timeFrame: 24 months
measure: Dose Expansion: Incidence and severity of dose limiting toxicities (DLTs) during the first cycle of monotherapy or combination treatment
timeFrame: 21 days
measure: Dose Expansion: Incidence and severity of AEs and SAEs by treatment
timeFrame: 24 months
measure: Dose expansion: Intracranial disease control rate (IDCR) per mRANO-BM
timeFrame: 24 months
measure: Dose expansion: Best overall intracranial response (BOIR) per mRANO-BM
timeFrame: 24 months
measure: Dose expansion: Intracranial progression free survival (IPFS) per mRANO-BM
timeFrame: 24 months
measure: Dose expansion: Duration of intracranial response (DOIR) per mRANO-BM
timeFrame: 24 months
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University School of Medicine-Winship Cancer Institute
state: Georgia
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Pittsburgh
country: United States
facility: Hillman Cancer Center
state: Pennsylvania
city: Houston
country: United States
facility: Uni Of TX MD Anderson Cancer Cntr
state: Texas
city: Melbourne
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Guangzhou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Beijing
country: China
facility: Novartis Investigative Site
city: Copenhagen
country: Denmark
facility: Novartis Investigative Site
city: Lyon
country: France
facility: Novartis Investigative Site
city: Marseille
country: France
facility: Novartis Investigative Site
city: Villejuif
country: France
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Freiburg
country: Germany
facility: Novartis Investigative Site
city: Koeln
country: Germany
facility: Novartis Investigative Site
city: Hong Kong
country: Hong Kong
facility: Novartis Investigative Site
city: Brescia
country: Italy
facility: Novartis Investigative Site
state: BS
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Nagoya
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Kashiwa
country: Japan
facility: Novartis Investigative Site
state: Chiba
city: Osaka-city
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Chuo ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Koto ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Amsterdam
country: Netherlands
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Malaga
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Hospitalet de LLobregat
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Santiago De Compostela
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Tainan
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
Study officials:
References:
citation: Lorthiois E, Gerspacher M, Beyer KS, Vaupel A, Leblanc C, Stringer R, Weiss A, Wilcken R, Guthy DA, Lingel A, Bomio-Confaglia C, Machauer R, Rigollier P, Ottl J, Arz D, Bernet P, Desjonqueres G, Dussauge S, Kazic-Legueux M, Lozac'h MA, Mura C, Sorge M, Todorov M, Warin N, Zink F, Voshol H, Zecri FJ, Sedrani RC, Ostermann N, Brachmann SM, Cotesta S. JDQ443, a Structurally Novel, Pyrazole-Based, Covalent Inhibitor of KRASG12C for the Treatment of Solid Tumors. J Med Chem. 2022 Dec 22;65(24):16173-16203. doi: 10.1021/acs.jmedchem.2c01438. Epub 2022 Nov 18.