Becotatug Vedotin Combined With Pucotenlimab ± Radiotherapy as First-Line Treatment for Driver-Gene-Negative, EGFR-Expression-Positive Advanced Non-Small Cell Lung Cancer

NCT07627321 | Not Yet Recruiting Phase 2

• 1 other identifier: PRAD2
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

This prospective, single-arm, exploratory multicenter clinical study aims to investigate the safety and efficacy of Becotatug vedotin combined with Pucotenlimab (with or without radiotherapy), followed by Pucotenlimab maintenance therapy, in patients with driver gene-negative (e.g., EGFR, ALK, ROS1), EGFR-overexpressing non-small cell lung cancer (NSCLC). Study Population: The study targets patients with driver gene-negative (EGFR, ALK, ROS1, and other actionable targets) non-squamous and squamous NSCLC. All subjects (regardless of smoking history) must provide testing reports for EGFR, ALK, and ROS1. If no prior report exists, baseline biopsy or submission of archived tissue for assessment of driver gene status (via local or central laboratory) is mandatory. Additionally, eligible patients must have an immunohistochemistry (IHC)-confirmed EGFR expression level of 2+ or higher, be previously untreated with systemic therapy for stage IV NSCLC, have measurable lesions, show no active central nervous system metastases or uncontrolled autoimmune diseases, and voluntarily sign the informed consent form. Treatment Regimen: Subjects meeting the inclusion/exclusion criteria will receive the following treatment regimen: Pucotenlimab (HX008): Administered from Cycle 1 to Cycle 4 at a dose of 3 mg/kg (maximum 200 mg), once every 3 weeks on Day 1 (D1). Intravenous infusion (60 ± 15 minutes; first cycle infusion duration not less than 60 minutes). Becotatug vedotin (MRG003): Administered from Cycle 1 to Cycle 4 at a dose of 2.0 mg/kg, once every 3 weeks on D1. Administration begins at least 30 minutes after the completion of Pucotenlimab infusion. Intravenous infusion (60 ± 10 minutes; first cycle infusion duration not less than 60 minutes). Radiotherapy: Investigators may opt to include sequential radiotherapy based on tumor size, number, location, extent of invasion, and individual patient factors. Radiotherapy options are as follows: Target Volume: Radiotherapy commences 2 weeks (±7 days) after the completion of Cycle 4 treatment, targeting only the primary tumor or specific 1-2 metastatic lesions. Fractionation and Dosage: Conventional Fractionation Group: Applicable for larger target volumes (\>5 cm diameter) or involvement of mediastinal lymph nodes. Total dose: 45-60 Gy; single fraction dose: 1.8-2.0 Gy; administered once daily (Qd). Stereotactic Body Radiotherapy (SBRT) Group: Applicable for oligometastatic lesions (≤3 lesions, each ≤3 cm diameter). Total dose: 30-50 Gy delivered in 3-5 fractions; single fraction dose: 6-10 Gy. Maintenance Therapy: Pucotenlimab (HX008) monotherapy until disease progression (defined by RECIST 1.1), investigator-assessed radiographic progression, unacceptable toxicity, withdrawal of consent, or fulfillment of criteria for discontinuation of intervention.

Conditions

NSCLC (Advanced Non-small Cell Lung Cancer)

Keywords

Becotatug vedotin; Pucotenlimab; Sequential radiotherapy; Driver gene-negative NSCLC

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  ORR is defined as the proportion of subjects achieving confirmed CompleteResponse (CR) or Partial Response (PR) as assessed by the investigator according to RECISTV1.1 and iRECIST criteria. ORR analysis will be based on the Full Analysis Set (FAS)

  up to 2 years

Secondary Outcomes (5)

• Disease Control Rate

  up to 2 years

• Progression-Free Survival

  up to 2 years

• Overall Survival

  up to 2 years

• .Duration of Response

  up to 2 years

• Safety Endpoints

  up to 2 years

Study Arms (1)

Experimental

EXPERIMENTAL

1. Pucotenlimab (HX008): Administered from Cycle 1 to Cycle 4 at a dose of 3 mg/kg (maximum 200 mg), once every 3 weeks on Day 1 (D1). IV. 2. Becotatug vedotin (MRG003): Administered from Cycle 1 to Cycle 4 at a dose of 2.0 mg/kg, once every 3 weeks on D1. IV. 3. Radiotherapy: Investigators may opt to include sequential radiotherapy based on tumor size, number, location, extent of invasion, and individual patient factors. Maintenance Therapy: Pucotenlimab monotherapy until disease progression (defined by RECIST 1.1), investigator-assessed radiographic progression, unacceptable toxicity, withdrawal of consent, or fulfillment of criteria for discontinuation of intervention.

Drug: Pucotenlimab; Drug: Becotatug vedotin; Radiation: Radiotherapy

Interventions

Pucotenlimab DRUG

Administered from Cycle 1 to Cycle 4 at a dose of 3 mg/kg (maximum 200 mg), once every 3 weeks on Day 1 (D1). Intravenous infusion (60 ± 15 minutes; first cycle infusion duration not less than 60 minutes). Maintenance Therapy: Pucotenlimab monotherapy until disease progression (defined by RECIST 1.1), investigator-assessed radiographic progression, unacceptable toxicity, withdrawal of consent, or fulfillment of criteria for discontinuation of intervention.

Experimental

Becotatug vedotin DRUG

Administered from Cycle 1 to Cycle 4 at a dose of 2.0 mg/kg, once every 3 weeks on D1. Administration begins at least 30 minutes after the completion of Pucotenlimab infusion. Intravenous infusion (60 ± 10 minutes; first cycle infusion duration not less than 60 minutes).

Experimental

Radiotherapy RADIATION

Investigators may opt to include sequential radiotherapy based on tumor size, number, location, extent of invasion, and individual patient factors.

Experimental

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntary participation with written informed consent obtained prior to any study-specific procedures, and willingness to comply with the study requirements.
• Male or female patients aged between 18 and 75 years (inclusive) at the time of signing informed consent.
• Histologically or cytologically confirmed Stage IV (M1a, M1b, or M1c according to the AJCC 8th Edition) squamous or non-squamous NSCLC.
• No prior systemic therapy for advanced/metastatic disease is permitted. Patients who received adjuvant/neoadjuvant chemotherapy and relapsed ≥6 months after the last dose are allowed to enroll.
• At baseline, presence of at least one measurable target lesion outside the primary tumor per RECIST v1.1, which is suitable for accurate repeated measurement and has not been previously irradiated or treated with other local therapies.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
• Absence of known actionable driver gene alterations (e.g., EGFR, ALK, ROS1) in both squamous and non-squamous NSCLC. All subjects (regardless of smoking history) must provide testing reports for EGFR, ALK, and ROS1. If no prior report exists, baseline biopsy or submission of archived tissue for assessment of driver gene status (via local or central laboratory) is mandatory.
• Immunohistochemistry (IHC)-confirmed EGFR expression level of 2+ or higher.
• Medically fit to tolerate radiotherapy, with an expected survival of ≥12 weeks.
• No prior exposure to Antibody-Drug Conjugates (ADCs).
• Adequate organ and bone marrow function as defined below (within 14 days prior to initiation of study treatment):
• \- Hematology (must not have received blood transfusions, granulocyte colony-stimulating factor \[G-CSF\], or hematopoietic growth factors within 14 days prior to screening):
• \- Hemoglobin (Hb) ≥ 90 g/L;
• \- Absolute Neutrophil Count (ANC) ≥ 1.5 × 10⁹/L;
• \- Platelets (PLT) ≥ 75 × 10⁹/L.

You may not qualify if:

• \. Prior receipt of any systemic anti-tumor therapy for advanced, recurrent, or metastatic NSCLC, or perioperative therapy completed less than 6 months prior to enrollment.
• \. History of another malignancy within 5 years prior to enrollment (excluding cured basal cell carcinoma of the skin or carcinoma in situ of the cervix).
• Known hypersensitivity to Becotatug vedotin, Pucotenlimab, or any of their excipients.
• \. Prior treatment with any of the following: ADCs, PD-1/PD-L1 inhibitors, CTLA-4 inhibitors, or bispecific antibodies targeting immune checkpoints.
• \. History of severe bleeding tendency or coagulation dysfunction; significant clinically significant bleeding symptoms within 1 month prior to the first dose (including but not limited to gastrointestinal bleeding, hemoptysis \[defined as expectoration of ≥1 teaspoon of fresh blood or blood clots, or pure hemoptysis without sputum; subjects with blood-streaked sputum are allowed\]); nasal hemorrhage (excluding simple epistaxis and post-nasal drip with blood); imaging at screening showing tumor encasement of major vessels, significant tumor necrosis, or cavitation deemed by the investigator to pose a high bleeding risk; central or cavitary squamous NSCLC deemed high-risk for bleeding by the investigator; receipt of continuous antiplatelet or anticoagulant therapy within 10 days prior to the first dose.
• \. Tumor invasion of surrounding vital organs or vessels (e.g., aorta, heart and pericardium, superior vena cava, trachea, esophagus) or presence of risk factors for esophagotracheal fistula or esophagopleural fistula.
• \. Subjects with uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage (subjects not requiring drainage or requiring drainage less than once per month are allowed).
• \. Arteriovenous thromboembolic events within 6 months prior to randomization, such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis (except those judged by the investigator to be fully resolved and related to venous catheters for prior chemotherapy), and pulmonary embolism.
• \. Symptomatic brain metastases. Subjects with brain metastases that have been treated and remain clinically stable for at least 1 month, and who have discontinued corticosteroids and anticonvulsants for at least 1 month prior to study entry, are allowed.
• \. Inability to provide documentation of driver gene-negative status or IHC evidence confirming EGFR expression ≥2+.
• Comorbidities/Medical History:
• \. Hypertension that cannot be adequately controlled with antihypertensive medication (systolic BP \>140 mmHg or diastolic BP \>90 mmHg);
• \- Within 6 months prior to randomization: myocardial infarction, severe/unstable angina, NYHA Class II or greater cardiac insufficiency, clinically significant supraventricular or ventricular arrhythmias, and symptomatic congestive heart failure;
• Conditions significantly affecting oral drug absorption, such as inability to swallow, chronic diarrhea, or clinically significant intestinal obstruction;
• Renal insufficiency: urinalysis indicating proteinuria ≥++, or confirmed 24-hour urine protein ≥1.0 g;

Sponsors & Collaborators

• Anhui Provincial Cancer Hospital: lead

Study Sites (1)

Anhui Provincial Cancer Hospital

Hefei, Anhui, 230031, China

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Radiotherapy

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Central Study Contacts

ShangHu Yuan, MD

CONTACT

86+ 13853106916; yuanshuanghu@sina.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 1, 2026
• First Posted: June 4, 2026
• Study Start (Estimated): July 15, 2026
• Primary Completion (Estimated): July 16, 2028
• Study Completion (Estimated): July 16, 2029
• Last Updated: June 4, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)