Advanced Solid Tumor
Conditions
Interventions
Group A:0.3mg/kg For the accelerated escalation group, one patient was enrolled and administered medication once every two weeks
Group B:0.6mg/kg For the accelerated escalation group, one patient was enrolled and administered medication once every two weeks
Group C:1.0mg/kg,The second and third patients can be enrolled only when the first patient has been observed for at least 3 days after the first administration and no DLT has occurred
Group D:1.3 mg/kg. Only after the first patient has received the drug and has been observed for at least 3 days without any DLT (grade 4 or 5 adverse event), can the second and third patients be enrol
Group E:1.6mg/kg. Only when the first patient has received the first dose and has been observed for at least 3 days without any DLT (grade 4 or 5 adverse event) can the second and third patients be en
Group F:1.8mg/kg. Only after the first patient has received the treatment and has been observed for at least 3 days without any DLT (grade 4 or 5 adverse event), can the second and third patients be e
Group G:2.0mg/kg ,The second and third patients can be enrolled only when the first patient has been observed for at least 3 days after the first administration and no DLT has occurred
Group H:On the premise of confirming t
Sponsors
Shanghai East Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: Patients must meet all of the following inclusion criteria to be eligible: 1. Know the trial information before the start of the study and voluntarily sign an informed consent form (ICF). 2. Aged >= 18 years, male or female. 3. Agree to follow and be capable of completing all study procedures. 4. Female weight > 45 kg, male weight > 50 kg, with a BMI >=18 kg/m^2. 5. Tumor Types Part I: Phase I Dose Escalation & Dose Expansion Phases of KY-0301 as monotherapy Patients with histologically or cytologically confirmed locally advanced or metastatic solid tumors [including but not limited to EGFR wild-type or mutant non-squamous non-small cell lung cancer (nsq-NSCLC, EGFRm, EGFRwt), squamous non-small cell lung cancer (sq-NSCLC), colorectal cancer (CRC), advanced gastric cancer/esophagogastric junction adenocarcinoma (GC/EGJA), and head and neck squamous cell carcinoma (HNSCC)]. Patients who have failed existing standard treatment regimens, are intolerant to standard treatment, have no standard treatment regimen, or are currently not suitable for standard treatment; Patients must have radiographically confirmed disease progression from the last antitumor treatment to the time of enrollment in this study. Part II: Phase II Cohort Expansion Phase of KY-0301 as monotherapy • Cohort A Histologically or cytologically confirmed locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) that is not suitable for curative surgery or radiotherapy. Patients with NSCLC carrying one or more EGFR-sensitive mutations that include L858R, 19Del, as confirmed by a qualified laboratory with tumor tissue or blood samples. Patients who have previously received first-line third-generation EGFR TKI therapy and have radiographic evidence of progression or documented disease progression or intolerance during or after treatment. For patients who have only received first- or second-generation EGFR TKI as first-line therapy, a negative report for the T790M mutation must be provided, without the need for treatment with a third-generation EGFR TKI; Patients must have received at least 1st line platinum-containing two-drug standard systemic chemotherapy; Patients must have radiographically confirmed disease progression from the last prior anticancer therapy to the enrollment in this study; Previous adjuvant or neoadjuvant therapy (excluding chemotherapy or radiotherapy involving Osimertinib) is allowed. • Cohort B Histologically or cytologically confirmed NSCLC with wild-type EGFR; Clear documentation showing that no actionable genetic mutations have been identified (e.g., EGFR activating mutations, ALK rearrangement, ROS1 rearrangement, KRAS mutations, BRAF mutations, NTRK fusions, MET exon 14 skipping mutation, fusion mutations, and ERBB2 mutations). For patients with positive PD-L1 expression, they have received at least first-line anti-PD - (L) 1 immunotherapy and chemotherapy for locally advanced or metastatic diseases; Patients must have radiographically confirmed disease progression from the last antitumor treatment to the time of enrollment in this study. • Cohort C Histologically or cytologically confirmed CRC. For patients with microsatellite instability-high (MSI-H) disease, at least one prior first-line anti-PD- (L) 1 immunotherapy and chemotherapy for locally advanced or metastatic disease; For recurrent/advanced metastatic disease, no chemotherapy above the 3rd line is received in the systemic treatment phase; Patients must have radiogra
Exclusion criteria
Exclusion criteria: Patients must be ineligible if they meet any of the following criteria: Previous/concomitant medications or treatments: 1. History of intolerance to ADC therapy composed of monomethyl auristatin E (MMAE). 2. Inadequate washout period of prior antitumor therapy prior to the first dose, defined as follows: • Any cytotoxic chemotherapy or small molecule targeted therapy 20 mg/day of prednisone or equivalent) or other immunosuppressive treatments within 2 weeks prior to first dose of the investigational drug, with the following exceptions: • Intranasal, inhaled, or local steroid injections (e.g., intra-articular injections); • Physiologic doses of systemic steroids as replacement therapy (e.g., physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency); • Use of steroids to prevent hypersensitivity reactions or to prevent antiemetic (e.g., computed tomography (CT) prophylaxis). 6. Received any live vaccine within 4 weeks prior to the first dose or plan to receive a live vaccine during the study. Medical history and concomitant diseases or examinations: 7. History of leptomeningeal carcinomatosis or carcinomatous meningitis. 8. Brain metastasis or spinal cord compression, except for: • Patients with asymptomatic brain metastases who have non-neoplastic lesions with no enlargement of the lesions and do not therapeutically require immediate local or systemic therapy (e.g., mannitol or corticosteroids) are eligible; • Patients with brain metastases that are stable after treatment of the metastases (brain imaging at least 4 weeks prior to the first dose shows stable lesions, no new neurological symptoms, and no immediate local or systemic treatment is required within 2 weeks prior to the first dose) and no evidence of new or enlarged original brain metastases are eligible; 9. Uncontrolled or clinically significant cardiovascular or cerebrovascular diseases, including but not limited to: • Symptomatic congestive heart failure within 6 months prior to the first dose [New York Heart Association (NYHA) Class II to IV, see Appendix 6], or any history of arterial thromboembolic events (e.g., myocardial infarction, unstable angina, cerebrovascular accident, transient ischemic attack), or experience of percutaneous coronary angioplasty
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of dose-limiting toxicities (DLTs) during the DLT observation period; Incidence and severity of adverse events (AEs); | — |
Secondary
| Measure | Time frame |
|---|---|
| Biomarker;Objective response rate;Median progression-free survival; | — |
Countries
China
Contacts
Public ContactCaicun Zhou
Shanghai East Hospital
Outcome results
None listed