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 Identifier:
CJDQ443A12101
CT.gov Identifier:
EudraCT Identifier:
EU Trial (CTIS) Number:
Study Contact Information:
N/A
Recruitment Complete
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Study Summary
To 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.
To assess the anti-tumor activity and further assess the safety, tolerability, and PK/PD of each regimen at the maximum tolerated dose / recommended dose.
To investigate the safety, tolerability, PK, pharmacodynamics (PD) and anti-tumor activity of JDQ443 single agent in adult patients with solid tumors carrying KRAS G12C mutations.
The main purpose of dose escalation:
To evaluate the safety and tolerability of JDQ443 as a single drug, and to determine the MTD and/or RD and dosing schedule for future studies.
The main purpose of the measurement expansion: to evaluate the anti-tumor activity of JDQ443 single agent.
Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
I/II
Sex
Female & Male
Age
18+ years
Study Drug
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Study Status
Indicates the current recruitment status or the expanded access status
Recruitment Complete
Requirements information
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
- Dose Escalation:
- Patients with advanced (metastatic or unresectable) KRAS G12C mutant solid tumors who have received and failed standard of care therapy or are intolerant or ineligible to approved therapies.
- Dose Expansion:
- Advanced (metastatic or unresectable) KRAS G12C mutant non-small cell lung cancer patients who are in the second or third line treatment setting who have received and failed a platinum-based chemotherapy regimen and immune checkpoint inhibitor therapy, unless patient refused or was ineligible to receive such therapy
- Advanced (metastatic or unresectable) KRAS G12C mutant colorectal cancer patients who have received and failed standard-of-care therapy, including a fluropyrimidine-, oxaliplatin-, and / or irinotecan-based chemotherapy, unless patient refused or was ineligible to such therapy.
- All Patients:
- ECOG performance status of 0 or 1.
- Patients must have a site of disease amenable to biopsy and be a candidate for tumor biopsy according to the institution’s own guidelines and requirements for such procedures.
- Inclusion criteria: advanced, KRAS G12C-mutated solid tumors; previous standard-of-care treatment; age ≥18 years; and ECOG PS 0–1.
- Key inclusion criteria include: adults with advanced, KRAS G12C-mutated solid tumors; previous standard-of-care treatment; ECOG PS 0-1.
Exclusion criteria
- Tumors harboring driver mutations that have approved targeted therapies, with the exception of KRAS G12C mutations.
- For the single-agent dose-escalation group and all dose-expansion patients, prior KRAS G12C inhibitor treatment must be excluded.
- For NSCLC patients who entered the dose expansion part of treatment group A (JDQ443 monotherapy), previous SHP2 inhibitor therapy is not allowed.
- symptomatic brain metastasis or known pia mater disease
- Symptomatic brain metastases or known leptomeningeal disease. Patients with asymptomatic treated or untreated brain metastases may be eligible
- History of allogeneic bone marrow or solid organ transplantation.
- Receive any of the following anti-cancer treatments within the prescribed time frame before the first dose of the study treatment: a. Received radiotherapy within < or = 4 weeks before the first dose of the study treatment, or received limited area palliative within < or = 2 weeks before the first dose of the study treatment Sexual radiotherapy. b. Previously received chemotherapy or biological therapy (including monoclonal antibodies) within < or = 4 weeks or < or = 5 half-lives (whichever is shorter), or received continuous or intermittent small molecule therapy or any other investigational drugs. c. Previously received cytotoxic drugs with significant delayed toxicity, such as nitrosoureas and mitomycin C, within = 6 weeks. d. Received immuno-oncology therapy within < or = 6 weeks before, such as CTLA-4, PD-1 or PD-L1 antagonist. e. Patients who have undergone major surgery or have not recovered after surgery within < or = 4 weeks before the first administration of the study treatment.
- Heart disease or risk factors of clinical significance at the time of screening
- Bone marrow insufficiency at screening
- Liver or kidney dysfunction during screening
- Unless otherwise specified in the inclusion/exclusion criteria, all clinically significant toxic reactions that occurred after previous systemic cancer treatment, surgery or radiotherapy have not been alleviated to < or = grade 1 (except for hair loss).
- Malignant diseases (except for diseases treated in this study). Exceptions to this standard include: receiving treatment for malignant tumors within 2 years prior to study treatment and cured without recurrence; completely resected basal cell and squamous cell skin cancers; malignant tumors that develop slowly and never require treatment; any completely resected Type of carcinoma in situ.
- Medical conditions leading to increased photosensitivity (ie solar urticaria, lupus erythematosus, etc.).
- There is current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (ie, history of uncontrolled glaucoma or high intraocular pressure, hyperviscosity or hypercoagulability syndrome, etc.).
- Unable to take the drug orally, or suffer from a medical disease that may affect the absorption of the study drug, or have previously undergone resection surgery that may affect the absorption of the study drug. Medical conditions that may affect the absorption of the study drug include (but are not limited to) inflammatory bowel disease (ie, ulcerative colitis, Crohn’s disease) and gastrointestinal diseases (such as ulcer disease, uncontrolled nausea, vomiting, diarrhea) And malabsorption syndrome).
- Patients who are known to be allergic to any study treatment drug or its excipients or similar chemical drugs.
- Patients who are taking banned drugs and cannot stop using such drugs at least 7 days before the first dose of study treatment and during the study period.
- Human immunodeficiency virus (HIV) infection. Unless there are clinical indications or local requirements, HIV status testing is not required.
- Active hepatitis B (HBV) and/or hepatitis C (HCV). Patients whose condition is under control after antiviral treatment can be selected. There is no need to test for HBV or HCV status unless there are clinical indications or the patient has a history of HBV or HCV infection.
- Participate in any additional parallel research drug or device research.
- Pregnant or lactating (lactating) women, pregnancy is defined as the state of a woman after pregnancy until the termination of pregnancy, confirmed by a laboratory test of human chorionic gonadotropin (hCG) positive
- Women with childbearing potential are defined as all women who are physiologically able to become pregnant, unless they continue to use effective contraceptive methods during the study treatment period and for 6 months after the study treatment is discontinued.
- According to the judgment of the investigator, any medical condition in which the patient cannot participate in the clinical research due to safety issues or compliance issues with the clinical research procedures. Any severe, acute or chronic medical or mental abnormality or abnormal laboratory test results may increase the risk related to research participation or research treatment, or may interfere with the interpretation of the research results, and may make the patient unsuitable for participation based on the judgment of the investigator the study
Clinical Study Information for Healthcare Providers
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Study Locations
Location
Investigator
Status
Condition(s) Treated at Site
Location
START Madrid, Spain (CIOCC)
Madrid, Spain, 28050
Investigator
Ramon Yarza
Status
Recruitment Complete
Condition(s) Treated at Site
Bowel (Colorectal)
Non-Small Cell Lung Cancer
Ovarian
Pancreas
Solid Tumor
Bile Duct