Phase Ib/II Study of Almonertinib Combined With SHR-1701 in the Treatment of Relapsed or Advanced Non-small Cell Lung Cancer

An Open-label, Multicenter Phase Ib/II Clinical Study of Almonertinib Combined With SHR-1701 or Other Innovative Drugs in the Treatment of Relapsed or Advanced Non-small Cell Lung Cancer With EGFR Mutation

To evaluate the tolerability, safety, pharmacokinetic characteristics and immunogenicity of Almonertinib combined with SHR-1701 in relapsed or advanced NSCLC To evaluate the efficacy of Almonertinib combined with SHR-1701 in the first-line treatment of relapsed or advanced NSCLC

Study Overview

• Status: Not yet recruiting
• Conditions: Relapsed or Advanced Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Almonertinib combined with SHR-1701; Drug: Almonertinib

• Study Type: Interventional
• Enrollment (Anticipated): 160
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Weixia Li; Phone Number: 0518-82342973; Email: weixia.li@hengrui.com
• Study Contact Backup: Name: Yanbo Liu; Phone Number: 0518-82342973; Email: yanbo.liu@hengrui.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients voluntarily joined the study and signed informed consent
2. Age 18~75 years old, both male and female
3. Advanced NSCLC diagnosed by histology or cytology, or recurrent NSCLC after radical treatment such as surgery, radiotherapy, chemoradiotherapy
4. At least one measurable lesion based on RECIST v1.1 criteria
5. ECOG PS score: 0-1
6. Have a life expectancy of at least 3 months
7. Fertile women must have a negative serum pregnancy test within 3 days before the first dose and must be non-lactating

Exclusion Criteria:

1. Untreated Brain metastases with clinical symptoms; Or accompanied by meningeal metastasis, spinal cord compression，etc.
2. Uncontrolled pleural, pericardial, or abdominal effusion with clinical symptoms
3. Suffering from other malignant tumors in the past 3 years or at the same time
4. Presence of any active or known autoimmune disease
5. Subjects who had been systematically treated with corticosteroids (>10 mg/ day of prednisone or other equivalent hormone) or other immunosuppressive agents within 2 weeks prior to the first dose (randomization)
6. Any severe or uncontrolled ocular lesions that, in the judgment of the investigator, may increase the subject's safety risk
7. Have clinical symptoms or diseases of the heart that are not well controlled
8. Patients with hypertension who are not well controlled by antihypertensive medication
9. Any bleeding event of grade 2 or more or hemoptysis (volume of hemoptysis ≥2ml in a single episode) occurring within 2 weeks before the first dose (randomization); Clinically significant bleeding symptoms or definite bleeding tendency before the first medication (randomization)
10. Have known history of serious infections within 1 month prior to the first dose(randomization), including but not limited to infectious complications that require hospitalization, bacteremia, and severe pneumonia; use antibiotics within 1 week prior to the first dose(randomization); have any active infections requiring intravenous systemic therapy, or have a fever > 38.5°C of unknown cause before the first dose(randomization).
11. Have active or prior documented interstitial pneumonia/interstitial lung disease or pneumonitis that requires glucocorticoid treatment (e.g., radiation pneumonitis); Have active pneumonia at present
12. Have active pulmonary tuberculosis.
13. Have known history of human immunodeficiency virus (HIV) seropositive status or acquired immunodeficiency syndrome (AIDS). Have known active hepatitis B or C.
14. Had received lung radiation therapy within 6 months before the first dose (randomization); Had received major surgical treatment (except diagnostic surgery), systemic chemotherapy, immunotherapy, or other investigational drugs within 4 weeks prior to the first medication (randomization); Received palliative radiotherapy within 2 weeks before the first dose (randomization); Oral administration of molecular targeted drugs, less than 5 half-lives before discontinuation of the drug to the first dose (randomization); Failure to recover from toxicity and/or complications of previous interventions to NCI-CTC AE grade≤1

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Almonertinib combined with SHR-1701	Drug: Almonertinib combined with SHR-1701; Phase Ⅰb/Phase Ⅱ： SHR-1701: injection, intravenous infusion Almonertinib: tablets, oral
Placebo Comparator: Almonertinib	Drug: Almonertinib; Phase Ⅱ: Almonertinib: tablets, oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose limiting toxicity （Phase Ib）		21 days after the first dose
The incidence and severity of ≥ grade 3 treatment-related adverse events (TRAE) and serious adverse events (TRSAE) in the combination of two drugs （Phase Ib）		from the time when all informed subjects signed the informed consent to the end of the safety follow-up period
PFS rate at 12 months	Progression-Free-Survival, defined as the time from randomization to the first occurrence of disease progression or death from any cause, whichever occurs first.	12 months after the first medication for the last subject

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DCR	Disease Control Rate, determined using RECIST v1.1 criteria	up to 3 years
DoR	Duration of Response, determined using RECIST v1.1 criteria	up to 3 years
Adverse Events and Serious Adverse Events		up to 3 years
Proportion of dose pauses, dose downgrades and dose terminations due to study-drug related toxicities during the trial		up to 3 years
ORR		up to 3 years
DepOR	Depth of tumor remission, determined using RECIST v1.1 criteria	up to 3 years
PFS	Progression-Free-Survival, determined using RECIST v1.1 criteria	up to 3 years
OS	OS is the time interval from the date of randomization to death due to any reason or lost of follow-up	up to 5 years

Collaborators and Investigators

• Sponsor: Suzhou Suncadia Biopharmaceuticals Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2022
• Primary Completion (Anticipated): July 30, 2027
• Study Completion (Anticipated): July 30, 2027

Study Registration Dates

• First Submitted: August 8, 2022
• First Submitted That Met QC Criteria: August 16, 2022
• First Posted (Actual): August 17, 2022

Study Record Updates

• Last Update Posted (Actual): August 17, 2022
• Last Update Submitted That Met QC Criteria: August 16, 2022
• Last Verified: August 1, 2022

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: SHR-1701-215

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No