Trial Title:
A Trial of SHR-A1811 Combined With Other Antitumor Therapies in Advanced Solid Tumors.
NCT ID:
NCT06015048
Condition:
HER2-expressing Advanced Solid Tumors
Conditions: Official terms:
Neoplasms
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
SHR-A1811 combined with Pyrotinib.
Description:
SHR-A1811 combined with Pyrotinib
Arm group label:
Part A: Intervention: Drug: SHR-A1811 combined with Pyrotinib
Intervention type:
Drug
Intervention name:
SHR-A1811 combined with other antitumor therapies
Description:
SHR-A1811 combined with other antitumor therapies
Arm group label:
Part B1: Intervention: Drug: SHR-A1811 combined with other antitumor therapies
Summary:
The study is being conducted to evaluate the safety, tolerability and efficacy of
SHR-A1811 combined with other antitumor therapies in advanced solid tumors. To explore
the reasonable dosage of SHR-A1811 combined with other antitumor therapies for advanced
solid tumors.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Able and willing to provide a written informed consent. Have good compliance and
cooperated with follow-up visits.
2. Subjects are older than or equal to 18 years old and younger than or equal to 75
years old on the day of signing the informed consent. Male or female.
3. ECOG score 0-1.
4. Life expectancy is at least 12 weeks.
5. Histologically or cytologically confirmed metastatic or advanced unresectable
HER2-expression or Her-2 functional mutations solid tumors.
6. Provide ≥ 6(or ≥8)sections of formalin-fixed, paraffin-embedded tumor tissue blocks
or unstained tumor specimen sections. Sections should be archived within 1 year
before the first study treatment or freshly obtained (freshly obtained is
preferred).
7. ≥1 Measurable lesions, according to the Response Evaluation Criteria for Solid
Tumors (RECIST) version 1.1. The dose escalation phase allows for the absence of
measurable lesions.
8. Organ function met criteria within 7 days prior to initial administration (No blood
component or cell growth factor was used within 14 days before the initial
administration):
9. Left ventricular ejection fraction (LVEF) ≥ 50% at baseline within 28 days prior to
initial administration.
10. Males and women of childbearing age must use reliable contraception from the written
informed consent to 7 months after last drug administration (SHR-A1811) or 8 weeks
after last drug administration (Pyrotinib) or 6 months after last drug
administration (BP102 or Oxaliplatin or Calcium levonofolinate or fluorouracil), the
latest time should be taken as final. Women of childbearing age must have had a
pregnancy test (serum or urine) with negative results within 7 days prior to initial
administration and must not in lactation period.
Exclusion Criteria:
1. Subjects with untreated or known active CNS metastasis. Subjects with a history of
meningeal metastasis or known active meningeal metastasis.
2. Have a history of antibody drug conjugate with following characteristics:
topoisomerase I inhibitors, including Enhertu (DS-8201a), U3-1402, etc. Part A: Have
a history of Her-2 targeted tyrosine-kinase inhibitor (TKI).
3. Palliative radiotherapy within 14 days prior to initial administration. Subjects who
had received systemic anti-tumor therapy within 4 weeks prior to initial
administration will not permitted. The interval between the end of small-molecule
targeted drugs administration and initial test drug administration must be ≥ 5
half-lives or 7 days (take the longer time). The interval between the end of Chinese
patent anti-tumor drug administration and initial test drug administration must be ≥
2 weeks. Participating in another clinical study of other drugs. The interval
between the previous clinical study drug use and this study initial administration
is less than 4 weeks or 5 half-lives of previous clinical study drug (take the
shorter time).
4. Toxicity and/or complications of previous interventions were not recovered to
NCI-CTCAE ≤ grade 1 or didn't meet this inclusion criteria and exclusion criteria.
If investigator determines that the toxicity and/or complications are NCI-CTCAE ≤
grade 2 and there is no safety risk, this subject can be enrolled. For example,
patients with type 1 diabetes or hypothyroidism who have been treated with immune
checkpoint inhibitors and are stable after hormone replacement therapy.
5. Have a history of (non-infectious) interstitial lung disease (ILD). Suspected ILD.
Other moderate and severe lung diseases that may interfere the detection or
management of drug-related pulmonary toxicity and severely affect respiratory
function within 3 months before the first test drug administration. Any autoimmune
disease, connective tissue disease, or inflammatory disease with lung involvement.
6. Patients unable to swallow orally administered medication and other disorders likely
to interfere the absorption of the study drugs within 28 days before the first test
drug administration.
7. Patients with moderate and severe ascites of clinical symptoms Refractory or
moderate to severe pleural effusion or pericardial effusion.
8. Patients with intestinal obstruction within 6 months prior to the first test drug
administration or presence of signs and symptoms of intestinal obstruction (patients
can be enrolled if surgical treatment had been performed and the obstruction had
been completely resolved).
9. Have clinically significant cardiovascular disease.
10. Previous or combined with other malignancies except those have achieved complete
remission and do not require or are not expected to require other treatment during
the study period within at least 5 years prior to screening, including basal cell
carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the
skin, cervical carcinoma in situ, local prostate cancer, ductal carcinoma in situ
after radical surgery, etc (hormone therapy for non-metastatic prostate cancer or
breast cancer is allowed) .
11. Serious infections within 28 days prior to the first test drug administration.
Active infections that had received therapeutic intravenous antibiotics within 2
weeks prior to the first test drug administration. Prophylactic antibiotic therapy
can be enrolled.
12. Active hepatitis B or active hepatitis C infection. Active hepatitis B is defined as
hepatitis B surface antigen (HBsAg) positive and HBV-DNA ≥10000 copies/ml [2000
IU/ml] during screening. Active hepatitis C is defined as hepatitis C virus antibody
positive and HCV-RNA positive during screening. Patients with active pulmonary
tuberculosis infection within 1 year before enrolment, or with a history of active
pulmonary tuberculosis infection but without regular treatment more than 1 year
before enrolment. Has known immunodeficiency disorders, including human
immunodeficiency virus (HIV) infection, etc. Received attenuated live vaccines
within 28 days of initial administration. Expected use of attenuated live vaccines
during the study period.
13. Major surgery history other than diagnostic or biopsy surgery within 28 days prior
to initial administration. Minor traumatic surgery within 7 days prior to initial
administration. Non-healing wounds. Untreated bone fractures.
14. Known allergy to any component of SHR-A1811. History of severe allergic reactions to
other monoclonal antibody/fusion protein drugs. Part A: known allergy to any
component of Pyrotinib.
15. Female subjects who are pregnant, in lactation period, or planning pregnancy during
the study period.
16. Uncontrolled mental illness and other conditions which will affect the completion of
the study, such as alcohol abuse, drug or substance abuse, criminal detention, etc.
17. Any other conditions that may not eligible to participate in this study according to
researchers' judgment.
For Part B1, subjects must not meet any of the following supplementary criteria at the
same time, otherwise they will not be enrolled in the study:
1、Presence of grade >1 peripheral neuropathy.
For those who plan to receive BP102 combination therapy, subjects must not meet any of
the following supplementary criteria at the same time, otherwise they will not be
enrolled in the study:
1. Bleeding tendency, coagulation dysfunction, or high risk of thrombosis.
2. Poorly controlled hypertension after medication (systolic blood pressure ≥ 140 mmHg
and/or diastolic blood pressure ≥ 90 mmHg in the case of regular anti-hypertensive
therapy) and prior hypertensive crisis or hypertensive encephalopathy. Severe
cerebrovascular diseases and clinically significant vascular diseases.
3. Severe cerebrovascular disease, including cerebrovascular accident (CVA), transient
ischemic attack (TIA), and significant vascular disease (including but not limited
to aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6
months prior to enrollment;
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Anhui Provincial Hospital
Address:
City:
Hefei
Zip:
230001
Country:
China
Status:
Recruiting
Investigator:
Last name:
Yubei Sun
Email:
Principal Investigator
Facility:
Name:
Peking University Cancer Hospital & Institute-Department of Gastrointestinal Oncology
Address:
City:
Beijing
Zip:
100142
Country:
China
Status:
Recruiting
Investigator:
Last name:
Lin Shen
Email:
Principal Investigator
Facility:
Name:
The First Affiliated Hospital of Chongqing Medical University
Address:
City:
Chongqing
Zip:
400016
Country:
China
Status:
Recruiting
Investigator:
Last name:
Tao Zhang
Email:
Principal Investigator
Facility:
Name:
Guangxi Medical University Affiliated Tumor Hospital
Address:
City:
Nanning
Zip:
530021
Country:
China
Status:
Recruiting
Investigator:
Last name:
Yongqiang Li
Email:
Principal Investigator
Facility:
Name:
The Fourth Hospital of Hebei Medical University
Address:
City:
Shijiazhuang
Zip:
050000
Country:
China
Status:
Recruiting
Investigator:
Last name:
Fengbing Zhang
Email:
Principal Investigator
Facility:
Name:
Harbin Medical University Cancer Hospital-The Eighth Department of Internal Medicine
Address:
City:
Harbin
Country:
China
Status:
Recruiting
Investigator:
Last name:
Yanqiao Zhang
Email:
Principal Investigator
Facility:
Name:
Henan Cancer Hospital
Address:
City:
Zhengzhou
Zip:
450003
Country:
China
Status:
Recruiting
Investigator:
Last name:
Yan Zhao
Email:
Principal Investigator
Facility:
Name:
The First Affiliated Hospital of Zhengzhou University-Department of Medical Oncology
Address:
City:
Zhengzhou
Zip:
450052
Country:
China
Status:
Recruiting
Investigator:
Last name:
Hong zong
Email:
Principal Investigator
Facility:
Name:
Hubei Cancer Hospital-Department of Abdominal Oncology
Address:
City:
Wuhan
Zip:
430079
Country:
China
Status:
Recruiting
Investigator:
Last name:
Xinjun Liang
Email:
Principal Investigator
Facility:
Name:
Hunan Cancer Hospital
Address:
City:
Changsha
Zip:
410031
Country:
China
Status:
Recruiting
Investigator:
Last name:
Zhenyang Liu
Email:
Principal Investigator
Facility:
Name:
The First Affiliated Hospital of Nanchang University
Address:
City:
Nanchang
Zip:
330006
Country:
China
Status:
Recruiting
Investigator:
Last name:
Xiaodong Peng
Email:
Principal Investigator
Facility:
Name:
The Second Affiliated Hospital of Nanchang University
Address:
City:
Nanchang
Zip:
330200
Country:
China
Status:
Recruiting
Investigator:
Last name:
Hua Wang
Email:
Principal Investigator
Facility:
Name:
Shanxi Provincial Cancer Hospital-Gastroenterology Department
Address:
City:
Taiyuan
Zip:
030013
Country:
China
Status:
Recruiting
Investigator:
Last name:
Wenhui Yang
Email:
Principal Investigator
Facility:
Name:
The First Affiliated Hospital of Xi'an Jiaotong University
Address:
City:
Xi'an
Zip:
710061
Country:
China
Status:
Recruiting
Investigator:
Last name:
Aili Suo
Email:
Principal Investigator
Facility:
Name:
Tianjin Medical University Cancer Institute and Hospital-Department of digestive oncology
Address:
City:
Tianjin
Zip:
300060
Country:
China
Status:
Recruiting
Investigator:
Last name:
Hongli Li
Email:
Principal Investigator
Start date:
August 11, 2023
Completion date:
December 29, 2026
Lead sponsor:
Agency:
Jiangsu HengRui Medicine Co., Ltd.
Agency class:
Industry
Source:
Jiangsu HengRui Medicine Co., Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06015048
