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

NCT04699188 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: CJDQ443A121012020-004129-22
• Study Type: interventional
• Target: 344
• Locations: 16 countries
• Sites: 38

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.

Conditions

KRAS G12C Mutant Solid Tumors; Carcinoma, Non-Small-Cell Lung; Carcinoma, Colorectal; Cancer of Lung; Cancer of the Lung; Neoplasms, Lung; Neoplasms, Pulmonary; Pulmonary Cancer; Pulmonary Neoplasms; Lung Cancer

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

Outcome Measures

Primary Outcomes (10)

• Dose Escalation: Incidence and severity of dose limiting toxicities (DLTs) during the first cycle of monotherapy or combination treatment

  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

  21 days

• Dose Escalation: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)

  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

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

  24 months

• Dose Escalation: Dose intensity by treatment

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

  24 months

• Dose Expansion: Overall response rate (ORR) per RECIST v1.1, by 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.

  24 months

• Dose expansion: Overall intracranial response rate (OIRR) per mRANO-BM

  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.

  24 months

• Dose expansion: Incidence and severity of AEs and SAEs

  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.

  24 months

• Dose expansion: frequency of dose interruptions and reductions, by treatment

  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.

  24 months

• Dose expansion: Dose intensity by treatment

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

  24 months

• Dose expansion: ORR per RECIST 1.1 of JDQ443 single agent in patients with non-small cell lung cancer (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

  24 months

Secondary Outcomes (17)

• Dose Escalation and Expansion: ORR per RECIST v1.1

  24 months

• Dose Escalation and Expansion: Best Overall Response (BOR) per RECIST v1.1

  24 months

• Dose Escalation and Expansion: Progression-free survival (PFS) per RECIST v1.1, Overall Survival (OS)

  24 months

• Dose Escalation and Expansion: Duration of Response (DOR) per RECIST v1.1

  24 months

• Dose Escalation and Expansion: Disease Control Rate (DCR) per RECIST v1.1

  24 months

Study Arms (4)

Arm A

EXPERIMENTAL

JDQ443

Drug: JDQ443

Arm B

EXPERIMENTAL

JDQ443 in combination with TNO155

Drug: JDQ443; Drug: TNO155

Arm C

EXPERIMENTAL

JDQ443 in combination with tislelizumab

Drug: JDQ443; Biological: tislelizumab

Arm D

EXPERIMENTAL

JDQ443 in combination with TNO155 and tislelizumab

Drug: JDQ443; Drug: TNO155; Biological: tislelizumab

Interventions

JDQ443 DRUG

KRAS G12C inhibitor

Arm A; Arm B; Arm C; Arm D

TNO155 DRUG

SHP2 inhibitor

Arm B; Arm D

tislelizumab BIOLOGICAL

Anti PD1 antibody

Arm C; Arm D

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (38)

Emory University School of Medicine-Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Uni Of TX MD Anderson Cancer Cntr

Houston, Texas, 77030, United States

Location

Novartis Investigative Site

Melbourne, Victoria, 3000, Australia

Location

Novartis Investigative Site

Leuven, 3000, Belgium

Location

Novartis Investigative Site

Montreal, Quebec, H2W 1T8, Canada

Location

Novartis Investigative Site

Guangzhou, Guangdong, 510080, China

Location

Novartis Investigative Site

Beijing, 100036, China

Location

Novartis Investigative Site

Copenhagen, DK-2100, Denmark

Location

Novartis Investigative Site

Lyon, 69373, France

Location

Novartis Investigative Site

Marseille, 13273, France

Location

Novartis Investigative Site

Villejuif, 94800, France

Location

Novartis Investigative Site

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

Location

Novartis Investigative Site

Cologne, North Rhine-Westphalia, 50937, Germany

Location

Novartis Investigative Site

Dresden, Saxony, 01307, Germany

Location

Novartis Investigative Site

Essen, 45147, Germany

Location

Novartis Investigative Site

Hong Kong, 999077, Hong Kong

Location

Novartis Investigative Site

Brescia, BS, 25123, Italy

Location

Novartis Investigative Site

Milan, MI, 20133, Italy

Location

Novartis Investigative Site

Milan, MI, 20162, Italy

Location

Novartis Investigative Site

Nagoya, Aichi-ken, 4668560, Japan

Location

Novartis Investigative Site

Kashiwa, Chiba, 2778577, Japan

Location

Novartis Investigative Site

Osaka, Osaka, 5418567, Japan

Location

Novartis Investigative Site

Chuo Ku, Tokyo, 1040045, Japan

Location

Novartis Investigative Site

Koto Ku, Tokyo, 1358550, Japan

Location

Novartis Investigative Site

Amsterdam, 1066 CX, Netherlands

Location

Novartis Investigative Site

Singapore, 119074, Singapore

Location

Novartis Investigative Site

Singapore, 168583, Singapore

Location

Novartis Investigative Site

Seoul, 03722, South Korea

Location

Novartis Investigative Site

Santiago Compostela, A Coruna, 15706, Spain

Location

Novartis Investigative Site

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Novartis Investigative Site

Barcelona, 08035, Spain

Location

Novartis Investigative Site

Madrid, 28050, Spain

Location

Novartis Investigative Site

Málaga, 29010, Spain

Location

Novartis Investigative Site

Valencia, 46010, Spain

Location

Novartis Investigative Site

Taipei, 10002, Taiwan

Location

Related Publications (1)

• 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.

  PMID: 36399068 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms; Lung Neoplasms; Neoplasm Metastasis

Interventions

JDQ443; tislelizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2021
• First Posted: January 7, 2021
• Study Start: February 24, 2021
• Primary Completion (Estimated): January 25, 2027
• Study Completion (Estimated): January 25, 2027
• Last Updated: March 18, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

BE (1); DK (1); NL (1); HK (1); DE (4); JP (5); CA (1); IT (3); US (5); FR (3); TW (1); KR (1); AU (1); SG (2); ES (6); CN (2)