Safety and Efficacy of NK510 to Treat NSCLC

First-in-Human Phase I Study of TIGIT-Blocked NK510 Cells in Patients With PD-1 Refractory Advanced NSCLC

This study assesses the safety and efficacy of NK510 combined with PD-(L)1 inhibitors for relapsed/refractory advanced NSCLC, with two administration routes: intravenous infusion and intrapleural perfusion for malignant pleural effusion. Eligible patients need confirmed measurable lesions; intravenous cohort requires EGFR/ROS1/ALK negativity and disease progression after PD-(L)1 inhibitor treatment, while intrapleural cohort accepts targeted therapy-resistant patients with ≥500ml pleural effusion, and the treatment's safety, efficacy and immune microenvironment changes will be evaluated.

Study Overview

• Status: Recruiting
• Conditions: NSCLC
• Intervention / Treatment: Drug: NK510; Drug: Tislelizumab，atezolizumab or sugemalimab; Drug: NK510; Drug: systemic therapy as selected by the investigator

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Jun Yan, PhD; Phone Number: +86 186 2166 8515; Email: yanjun@basetherapeutics.com
• Study Contact Backup: Name: Tangfeng Lv; Phone Number: +86 139 5201 6932; Email: bairoushui@163.com

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Recruiting
      • Jinling hospital, affiliated to Medical school Nanjing University
      • Contact: Tangfeng Lv; Phone Number: +86 139 5201 6932; Email: bairoushui@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years, male or female.
• For dose expansion group (Group A/B/C):

A. EGFR mutation-negative, ROS1-negative, and ALK-negative; unresectable and non-radiotherapeutic stage III or IV, locally advanced, recurrent or metastatic NSCLC.

B. Disease progression after ≥4 courses of PD-(L)1 blockade ± chemotherapy.

• For pleural perfusion group (Group D1/D2): Advanced NSCLC with malignant pleural effusion ≥500ml (confirmed by B-ultrasound or CT); patients with driver gene-positive and resistant to targeted therapy are acceptable.
• At least one CT or MRI measurable lesion according to RECIST v1.1.
• ECOG performance status 0-2.
• Expected survival ≥3 months.
• All toxicities from previous anti-tumor therapy (except alopecia and fatigue) resolved to grade 1 (CTCAE v5.0) or baseline; subjects with long-term sequelae from previous therapy (e.g., neuropathy after platinum-based therapy) are acceptable.
• Fertile females must be non-lactating and have a negative serum pregnancy test within 1 week before enrollment; all subjects (male or female) must agree to use contraception from signing informed consent until 6 months after the last NK510 infusion.
• Able to comply with the study protocol and follow-up procedures.
• Voluntarily sign the informed consent form.

Exclusion Criteria:

• Symptomatic central nervous system (CNS) metastasis and/or carcinomatous meningitis.
• Active, known or suspected autoimmune diseases (excluding type 1 diabetes, hypothyroidism requiring only hormone replacement therapy, skin diseases not requiring systemic treatment [e.g., vitiligo, psoriasis, alopecia] or diseases not expected to recur without external triggers).
• History of severe cardiovascular and cerebrovascular diseases, including but not limited to: severe cardiac arrhythmia or conduction abnormalities requiring clinical intervention (e.g., ventricular arrhythmia, grade III atrioventricular block); QTc interval >480 ms on 12-lead ECG at rest; acute coronary syndrome, congestive heart failure, aortic dissection, stroke or other grade ≥3 cardiovascular and cerebrovascular events within 6 months before enrollment; NYHA cardiac function class ≥II or left ventricular ejection fraction (LVEF) <50%; clinically uncontrolled hypertension.
• Blood transfusion, erythropoietin, granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor treatment within 2 weeks before enrollment.
• Systemic treatment with corticosteroids (prednisone >10 mg/day or equivalent) or other immunosuppressive/immunomodulatory drugs (e.g., thymosin, interleukin-2, interferon) within 2 weeks before enrollment; inhalation or topical corticosteroids are allowed in subjects without active autoimmune diseases.
• Known allergy or intolerance to PD-(L)1 blockade.

• Meeting any of the following laboratory criteria:

  1. Hematology: Neutrophils <1.5×10⁹/L; Platelets <75×10⁹/L; Hemoglobin <90 g/L.
  2. Liver function: ALT >3×ULN (≥5×ULN in patients with liver metastasis); AST >3×ULN (≥5×ULN in patients with liver metastasis); TBIL >1.5×ULN or >2.5×ULN (3.0 mg/dL) in patients with Gilbert syndrome.
  3. Renal function: Serum creatinine >1.5×ULN or creatinine clearance <50 mL/min.
• Any other severe or uncontrollable medical diseases, active infections, physical examination abnormalities, laboratory test abnormalities, mental status changes or mental illnesses that increase subject risk or affect study results (assessed by investigator).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A (low-dose group); NK510 will be administered once a week for a total of six weeks.3×10^9 NK cells/dose. PD-1 blockade will be administered every 1 or 3 weeks, depending on PD-1 blockade chosed by investigator.	Drug: NK510; Intravenous infusion; Drug: Tislelizumab，atezolizumab or sugemalimab; Administer according to the instructions; Drug: NK510; intrapleural infusion
Experimental: Group B (medium-dose group); NK510 will be administered once a week for a total of six weeks.9×10^9 NK cells/dose. PD-1 blockade will be administered every 1 or 3 weeks, depending on PD-1 blockade chosed by investigator..	Drug: NK510; Intravenous infusion; Drug: Tislelizumab，atezolizumab or sugemalimab; Administer according to the instructions; Drug: NK510; intrapleural infusion
Experimental: Group C (high-dose group); NK510 will be administered once a week for a total of six weeks.12×10^9 NK cells/dose. PD-1 blockade will be administered every 1 or 3 weeks, depending on PD-1 blockade chosed by investigator..	Drug: NK510; Intravenous infusion; Drug: Tislelizumab，atezolizumab or sugemalimab; Administer according to the instructions; Drug: NK510; intrapleural infusion
Experimental: Group D1 (low-dose group); Thoracic perfusion therapy will be conducted on Day 1 (D1) and Day 5 (D5) of each 3-week treatment cycle, with 3×10⁹ NK510 cells/dose for each time via intrapleural infusion, for 2 consecutive cycles.	Drug: NK510; Intravenous infusion; Drug: NK510; intrapleural infusion; Drug: systemic therapy as selected by the investigator; Administer according to the instructions
Experimental: Group D2 (high-dose group); Thoracic perfusion therapy will be administered on Day 1 (D1) and Day 5 (D5) of each 3-week treatment cycle, with 6×10⁹ NK510 cells/dose for each time via intrapleural infusionwith, for 2 consecutive cycles.	Drug: NK510; Intravenous infusion; Drug: NK510; intrapleural infusion; Drug: systemic therapy as selected by the investigator; Administer according to the instructions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-limiting toxicity and incidence of adverse events	To evaluate DLT and the incidence of AEs associated with NK510 treatment	6 weeks
Objective Response Rate	For intravenous groups: Proportion of subjects achieving CR and PR according to RECIST v1.1 after first NK510 administration; For pleural perfusion groups: Proportion of subjects achieving CR and PR according to WHO criteria after first NK510 intrapleural perfusion.	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival	Time from first NK510 administration to disease progression or death.	From the date of the first dose of NK510 until disease progression, death, or a maximum of 24 months after the first dose, whichever occurs first.
Puncture-Free Survival	Time from last treatment puncture to next puncture drainage (for pleural perfusion groups).	From the date of the last treatment puncture to the date of the next puncture drainage, or up to a maximum of 24 months after the last treatment puncture, whichever occurs first.
Duration of Response	Time from achievement of response to disease progression.	From the date of first documentation of objective response to disease progression, death, or a maximum of 24 months after the date of first response, whichever occurs first.
Disease Control Rate	Proportion of subjects achieving CR, PR or SD based on baseline tumor assessment.	From baseline tumor assessment up to the earliest of disease progression，or a maximum of 24 months after baseline.
Overall Survival	Time from screening enrollment to death.	From the date of screening enrollment to death, or a maximum of 24 months after screening enrollment, whichever occurs first.
Health-Related Quality of Life	Assessed by EORTC QLQ-C30 (V3.0) scale.	At screening, every 6 weeks during treatment, at study completion, or up to a maximum of 24 months after the first dose, whichever occurs first.

Collaborators and Investigators

• Sponsor: Base Therapeutics (Shanghai) Co., Ltd.
• Collaborators: Jinling Hospital, China
• Investigators: Principal Investigator: Tangfeng Lv, PhD, Jinling hospital, Nanjing, China

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2023
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: October 17, 2023
• First Submitted That Met QC Criteria: October 17, 2023
• First Posted (Actual): October 24, 2023

Study Record Updates

• Last Update Posted (Actual): May 20, 2026
• Last Update Submitted That Met QC Criteria: May 18, 2026
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Malignant Pleural Effusion
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Pleural Neoplasms; Pleural Diseases; Pleural Effusion; Pleural Effusion, Malignant; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; sugemalimab
• Other Study ID Numbers: NK510-06

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No