A First-in-human Study of KY-0301 in Patients With Advanced Solid Tumors.

Phase 1

Not yet recruiting

• Conditions: Solid Tumors
• Interventions: Drug: KY-0301

• Registration Number: NCT06928363
• Lead Sponsor: Novatim Immune Therapeutics (Zhejiang) Co., Ltd.

Brief Summary

This trial is a first-in-human, multicenter, open-label Phase I/II clinical study to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of KY-0301 as monotherapy in patients with advanced solid tumors. This trial will be conducted at approximately multi-sites nationwide, and approximately110\~212 participants with unresectable locally advanced or metastatic solid tumors will be invited to participate. The study consists of three parts: Phase I dose escalation \& dose expansion phases of KY-0301 as monotherapy, Phase II cohort expansion phase of KY-0301 as monotherapy.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-03
• Study First Submitted: 2025-03-31
• Study First Submitted QC: 2025-04-07
• Last Update Submitted: 2025-04-07
• Study First Posted: 2025-04-15
• Last Update Posted: 2025-04-15
• Study Start: 2025-05-01
• Primary Completion: 2027-11-12
• Study Completion: 2027-12-15

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 212

Inclusion Criteria

• Know the trial information before the start of the study and voluntarily sign an informed consent form (ICF).
• Aged ≥ 18 years, male or female.
• Agree to follow and be capable of completing all study procedures.
• Female weight > 45 kg, male weight > 50 kg, with a BMI ≥18 kg/m2
• Tumor Types:

Part I, Patients with histologically or cytologically confirmed locally advanced or metastatic solid tumors; 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.

Part II, Cohort A: Histologically or cytologically confirmed locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) ;Patients who have previously received EGFR TKI and 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. Cohort B: Histologically or cytologically confirmed NSCLC with no actionable genetic mutations have been identified ；have received at least first-line anti-PD - (L) 1 immunotherapy and chemotherapy . Cohort C :Histologically or cytologically confirmed CRC; Patients who have previously received SoC; chemotherapy above the 3rd line is received in the systemic treatment phase. Cohort D: other histologically or cytologically confirmed locally advanced or metastatic solid tumors

Exclusion Criteria

• History of intolerance to ADC therapy composed of monomethyl auristatin E (MMAE).
• Inadequate washout period of prior antitumor therapy prior to the first dose
• Patients who have undergone major surgery (excluding diagnostic surgery) within 4 weeks prior to first dose or those who plan to undergo major surgery during the study period. Interventional or ablative procedures for tumor treatment within 2 weeks prior to the first dose of the investigational drug.
• Previous allogeneic bone marrow transplantation or previous solid organ transplantation.
• Systemic steroid use (>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).
• Received any live vaccine within 4 weeks prior to the first dose or plan to receive a live vaccine during the study.
• History of leptomeningeal carcinomatosis or carcinomatous meningitis.
• Brain metastasis or spinal cord compression, except for Patients with asymptomatic brain metastases
• Uncontrolled or clinically significant cardiovascular or cerebrovascular diseases
• Clinically significant concomitant pulmonary diseases
• Patients with symptomatic or unstable third-spacing (e.g., pleural effusion, ascites, pericardial effusion) require repeated drainage.
• History of gastrointestinal perforation and/or fistula within 6 months prior to the first dose, or the presence of active gastric ulcer, duodenal ulcer, ulcerative colitis, gastrointestinal obstruction, or any other gastrointestinal disease that the investigator deems may cause bleeding or perforation.
• Patients with severe infection [≥ Grade 3 per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0] prior to first dose
• Patients with HIV infection or those who test positive for syphilis antibodies with a positive titer test.
• Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Active HBV is defined as positive hepatitis B surface antigen (HBsAg) and/or positive hepatitis B core antibody (HBcAb), with HBV DNA levels above the detectable lower limit of the study site; active HCV is defined as positive hepatitis C antibodies with HCV RNA levels above the detectable lower limit of the study site.
• Non remission of toxicity from previous anticancer therapy is defined as non remission of toxicity (other than alopecia and pigmentation) to NCI CTCAE v5.0 ≤ Grade 1, baseline, or inclusion/exclusion criteria. Patients with chronic Grade 2 toxicities may be eligible for enrollment if the toxicity is asymptomatic or adequately controlled with stable medication, after discussion with the sponsor.
• History of severe allergic reactions to drugs
• Any other primary malignancy within 5 years prior to first dose of the investigational drug, except for low-risk tumors such as adequately resected basal cell skin cancer, cervical carcinoma in situ, or papillary thyroid carcinoma .etc.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Dose escalation/Expansion：KY-0301	KY-0301	KY-0301, 0.3 mg/kg\~ 2.0 mg/kg.i.v. Q2W，4 weeks/cycle
Cohort A:EGFRm NSCLC	KY-0301	KY-0301, .i.v. Q2W，4 weeks/cycle
Cohort B:EGFRwt NSCLC	KY-0301	KY-0301, 0.3 mg/kg\~ 2.0 mg/kg.i.v. Q2W，4 weeks/cycle
Cohort C:CRC	KY-0301	KY-0301, 0.3 mg/kg\~ 2.0 mg/kg.i.v. Q2W，4 weeks/cycle
Cohort D: other solid tumor	KY-0301	KY-0301, 0.3 mg/kg\~ 2.0 mg/kg.i.v. Q2W，4 weeks/cycle

Primary Outcome Measures

Name	Time	Method
Occurrence of dose-limiting toxicity (DLT)	28 days	DLT is defined as an adverse event (AE) that meets protocol defined DLT criteria during cycle 1 and is at least possibly related to study drug.
MTD	Up to 24 Months	The maximum tolerated dose (MTD) is defined as the maximum dose where the number of cases of DLT ≤ 1/6 of the total number of cases during the DLT observation period. At least 6 evaluable subjects are required to determine MTD.

Secondary Outcome Measures

Name	Time	Method
The area under curve (AUC) of KY-0301 (ADC) in plasma	Up to 24 Months	Area under the plasma concentration versus time curve
The immunogenicity of KY-0301	Up to 24 Months	Occurrence of anti-drug antibodies (ADA)
Progression-free survival (PFS)	Up to 24 Months	PFS is defined as time from first study treatment to a documented disease progression according to RECIST, version 1.1, as determined by the investigator, or death due to any cause, whichever occurs earlier.
The maximum concentration (Cmax) of KY-0301 in plasma	up to 24 months	The Peak Plasma Concentration of KY-0301 in plasma
Objective response rate (ORR)	Up to 24 Months	defined as percentage of participants with confirmed best overall response of confirmed partial response (PR) or better per investigator review according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.