A Study of Sunvozertinib Combined With Anlotinib in Local Advanced or Metastatic Non-small Cell Lung Cancer (WUKONG-9)

Efficacy and Safety of Sunvozertinib With Anlotinib in EGFR-TKIs Resistant EGFR-sensitive Mutated Locally Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC): a Prospective, Single-arm, Phase II Trial

The study will evaluate the efficacy and safety of treatment with sunvozertinib in combination with Anlotinib in patients whose disease has progressed following first-line EGFR-TKIs treatment.

Study Overview

• Status: Not yet recruiting
• Conditions: NSCLC
• Intervention / Treatment: Drug: Sunvozertinib combination with Anlotinib

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol.
2. Pathologically confirmed non-squamous NSCLC. Locally advanced or metastatic NSCLC
3. EGFR sensitive mutations confirmed by accredited local laboratories， including 19del、L858R and T790M。
4. Intolerant or refuses, or not suitable for systemic chemotherapy.
5. Progressed after EGFR-TKI targeted therapy or are intolerant to standard treatment; if carry T790M mutation, need to be treated with osimertinib or other third-generation EGFR-TKI.
6. World Health Organization performance status of 0 to 1
7. Life expectancy >12 weeks at Day 1.
8. At least 1 lesion to be measured
9. Females must be using highly effective contraceptive measures, and must have a negative pregnancy test prior to start of dosing if of childbearing potential, or must have evidence of non-childbearing potential by fulfilling criteria at screening.
10. Male patients must be willing to use barrier contraception

Exclusion Criteria:

1. Any known RET rearrangement, BRAF V600E mutation, NTRK fusion, MET ex14 skip mutation, MET amplification (defined as tissue detection GCN ≥ 5 by NGS)
2. Any concurrent and/or other active malignancy within 2 years
3. Major surgery within 4 weeks of the first dose of IP
4. Any unresolved toxicities from prior therapy.
5. Past medical history of ILD (interstitial lung disease)/pneumonitis, drug-induced ILD/pneumonitis, radiation pneumonitis that required steroid treatment, or any evidence of clinically active ILD/pneumonitis
6. Any evidence of severe or uncontrolled systemic diseases.

7. Any of the following cardiac criteria:

   i) Mean resting QTc >470 msec ii) Any clinically important abnormalities in rhythm, conduction, or morphology of resting electrocardiogram iii) Any factors that increase the risk of QTc prolongation or risk of arrhythmic events

8. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of Sunvozertinib and Anlotinib
9. Severe allergies to Sunvozertinib and Anlotinib

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: sunvozertinib in combination with Anlotinib	Drug: Sunvozertinib combination with Anlotinib; Sunvozertinib 300 mg once daily (QD) with Anlotinib 12mg once daily （QD in Day 1-14） ，21 days in one cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	Objective response rate (ORR) as assessed by the investigator according to RECIST 1.1 criteria.	initiate from first dose until the date of confirmed response, assessed up to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	PFS as assessed by the investigator according to RECIST 1.1	initiate from first dose, every 6 weeks until PD or study close, an average of 1 year
OS	initiate from first dose to death from any cause	through study completion, an average of 1.5 years
DoR	The period from the first judgment of CR or PR to PD	an average of 1 year
AE	TRAE as assessed by the investigator according to CTCAE 5.0	through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Shanghai Zhongshan Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2024
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: December 1, 2023
• First Submitted That Met QC Criteria: December 26, 2023
• First Posted (Actual): December 27, 2023

Study Record Updates

• Last Update Posted (Actual): December 27, 2023
• Last Update Submitted That Met QC Criteria: December 26, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: WUKONG9

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