๐ฌIn plain words
What the trial is, and whether it could suit you
This is a multicenter, open-label, phase I clinical study employing a dose-escalation and cohort-expansion design to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of CSCJC3456 in patients with advanced malignant solid tumors.
Sign in to get the eligibility rules as simple questions to take to your doctor.
๐ Eligibility rules (as published)
Inclusion Criteria:
1. Voluntarily sign the informed consent form and follow protocol requirements;
2. Aged 18 to 75 (both inclusive), male or female, regardless of race;
3. Expected survival period โฅ 12 weeks;
4. ECOG PS score โค1;
5. Phase Ia study:
โ Participants with advanced malignant solid tumors confirmed by pathology or cytology, who have experienced disease progression despite standard treatment, are intolerant to standard treatment, or lack effective standard treatment; and who possess at least one measurable lesion in accordance with RECIST v1.1 criteria;
Phase Ib study:
* Cohort A (hepatocellular carcinoma, including at least 2 participants with FGFR4 positivity), Cohort B (colorectal cancer, including at least 2 participants with FGFR1 or FGFR2 positivity), Cohort C (gastric cancer (including adenocarcinoma at the gastroesophageal junction), including at least 2 participants with FGFR1 or FGFR2 positivity), Cohort D (recurrent/metastatic endometrial cancer, including at least 2 participants with FGFR2 or FGFR3 positivity), or other sensitive tumor types identified in phase Ia trial, confirmed by histology or cytology, who have failed or are intolerant to standard treatment. Investigators may adjust participant selection based on their response to treatment in the trial and communication with the sponsor.
* Each cohort of participants had at least one measurable lesion that met the criteria of RECIST v1.1.
6. Before the first dose, the participant has recovered from the toxic effects of the previous last treatment (CTCAE grade โค 1, except for special conditions such as "hair loss" and "pigmentation"), and in addition, the investigator judges that the corresponding AE did not pose a safety risk;
7. Systolic blood pressure โค150 mmHg, diastolic blood pressure โค90 mmHg, and no changes in antihypertensive medication and dosage within 7 days prior to the first administration.
8. Adequate Organ and bone marrow function.
9. Female participants of childbearing age must undergo a serum pregnancy test 7 days before starting the study medication, and the result must be negative. They must also be willing to adopt a medically approved highly effective contraceptive measure (e.g., an intrauterine device, contraceptive pills, or condoms) during the study period and for 3 months after the last administration of study medication. Male participants whose partners are female of childbearing age should agree to adopt an effective contraceptive method during the study period and for 3 months after the last administration of study medication. Breastfeeding women should agree to cease breastfeeding during the study period and for 3 months after the last administration of study medication.
10. Have the gene sequencing results of the current tumor, or are willing to provide tumor tissue specimens (paraffin-embedded tissue blocks, or serial sections).
* Specimens are preferably derived from recently collected and usable tumor tissues. For relevant instructions, please refer to the Central Laboratory Manual.
* In cases where there is insufficient tumor tissue (e.g., insufficient number of available slides, including situations where no tissue specimens are available) and the investigator believes that another tumor tissue biopsy is unsafe, intolerable, infeasible, or the patient refuses, the patient can be enrolled in the study after discussion with the sponsor.
Exclusion Criteria:
1. Previous or current diagnosis of other types of malignancy, except for the following:
1. Radically cured basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, cervical carcinoma in situ, or breast cancer in situ;
2. Second primary cancer that has been cured with no recurrence within 5 years;
2. Patients who are allergic to any component of the study drug or have a history of severe allergies;
3. Having received any of the following treatments or medications before the first study treatment:
1. Major surgery or major trauma occurred within 4 weeks before the first study drug, but diagnostic tissue biopsies are allowed. Severe trauma refers to unhealed wounds, ulcers, or fractures;
2. Received treatment with traditional Chinese patent medicines and simple preparations with anti-tumor indications within 2 weeks before the first study drug treatment;
3. Received anti-neoplastic therapies (including chemotherapy, radiotherapy, immunotherapy, targeted therapy, biologic therapy, or tumor embolization) within 4 weeks or 5 half-lives of the investigational drug prior to the first dose, whichever is shorter;
4. Have received a potent CYP2C8 or CYP3A4 inducer within 2 weeks before the first dose; Or have received potent CYP2C8 or CYP3A4 inhibitors with less than 5 half-lives before the first dose;
5. Have received medications known to significantly prolong the QT interval (e.g., class Ia and class III antiarrhythmic drugs) within 1 week or 5 half-lives of the investigational drug prior to the first dose, whichever is shorter;
6. Previously received treatment with FGFR inhibitors (e.g., pemetrexed, erdafilone, infigranib, forodesine, ponatinib, dovitinib, nintedanib, AZD4547, NVP-BGJ398, LY2874455, BAY1163877, etc.);
4. Patients with a history of central nervous system metastasis or spinal cord compression. Those who meet the following criteria can be enrolled:
1. Patients who have clearly received treatment and have been clinically stable for 4 weeks after discontinuing anticonvulsants and steroids prior to the first administration of the study drug (definition of clinical stability: no clinical accompanying symptoms such as intracranial hypertension or neurological symptoms within 4 weeks, and imaging findings indicating stable lesions within 4 weeks prior to the first administration of the drug);
2. For patients with brain metastases, โฅ21 days from whole brain radiation therapy (WBRT) to the first study treatment administration,