Trial Title:
RC48 Monotherapy or Combination With Envafolimab for CDK12 Alterations mCRPC With Standard Treatment Failure
NCT ID:
NCT06663007
Condition:
Prostate Cancer
CDK12 Gene Mutation
Conditions: Official terms:
Prostatic Neoplasms
Disitamab vedotin
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Single Group Assignment
Intervention model description:
Simon's two-stage design.If the number of valid cases in the first stage is less than or
equal to 0, the study will be terminated prematurely. If the number of valid cases in the
first stage is greater than 0, participants will continue to be enrolled in the second
stage. If the total number of valid cases is greater than 3 after the completion of the
second stage, the queue experimental group is considered valid.
Primary purpose:
Treatment
Masking:
Single (Investigator)
Intervention:
Intervention type:
Drug
Intervention name:
RC48
Description:
During the patient treatment phase, the subjects received intravenous infusion of
Disitamab Vedotin(RC48) (2.0 mg/kg) every 2 weeks until disease progression or death
occurred.
Arm group label:
Cohort A
Arm group label:
Cohort B
Other name:
Disitamab Vedotin
Intervention type:
Drug
Intervention name:
Envafolimab
Description:
During the treatment phase of the patient, the subjects received subcutaneous injections
of Envafolimab (400 mg) every 3 weeks until the patient experienced disease progression
or death.
Arm group label:
Cohort A
Summary:
The aim of this study is to evaluate the efficacy and safety of vediximab monotherapy or
in combination with enrolizumab for second-line treatment of CDK12 alterations mCRPC that
has failed standard therapy. The research results are expected to provide new insights
and breakthroughs for the treatment of advanced prostate cancer.
Detailed description:
This study plans to enroll 72 mCRPC patients who have failed at least one NHT standard
treatment and have exhausted PARPi treatment (such as AVPC/NEPC, requiring platinum
chemotherapy resistance or intolerance). The patient carries CDK12 mutation combined with
ERBB amplification (NGS or FISH) or HER2 IHC (1+, 2+, 3+). The enrolled patients were
divided into queue A and queue B based on whether they carried potential immunotherapy
adverse factors (including chromosome instability mutation profiles such as 11q13 co
amplification, MDM2/4 amplification, FGFRs amplification, etc.). During the treatment
phase of patients in queue A (excluding CDK12mut from mutation spectrum features in queue
B), subjects received intravenous infusion of vediximab (2.0 mg/kg) every 2 weeks, in
combination with subcutaneous injection of bevacizumab (400 mg) every 3 weeks, until
disease progression or death occurred. During the treatment phase, subjects in queue B
(CDK12mut combined with 11q13 co amplification, MDM2/4 amplification, FGFRs amplification
and other chromosomal unstable mutation profiles) received intravenous infusion of
vediximab (2.0 mg/kg) every 2 weeks until disease progression or death occurred. The main
endpoint of the study was hierarchical testing, Step 1: ORR in CDK12 mut mCRPC with ERBB2
IHC 3+or FISH+or ERBB amplification (CN ≥ 4); Step2: ORR in ITT。 The secondary endpoints
of the study include PSA50, PFS, OS, and safety.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Participants must be able to understand the procedures and methods of this study,
willing to strictly follow the clinical trial protocol to complete the trial, and
voluntarily sign a written informed consent form;
2. Patients aged ≥ 18 years old;
3. Pathological examination confirms non resectable or metastatic HER2 positive
castration resistant prostate cancer (mCRPC): HER2 positive is defined as IHC 3+or
IHC 2+or FISH+;
4. Carrying CDK12 mutation combined with ERBB amplification (NGS or FISH) or HER2 IHC
(1+, 2+, 3+);
5. According to the RECIST solid tumor efficacy evaluation criteria, there must be at
least one measurable lesion;
6. ECOG PS: 0-2 points;
7. Expected survival period is not less than 12 weeks;
8. Prior exposure to at least one novel endocrine therapy (including abiraterone,
enzalutamide, darotamine, apatamide, and rivalutamide) and depletion of PARPi
treatment (if AVPC/NEPC, platinum chemotherapy resistance or intolerance is
required);
9. Have not used HER2 targeted drugs (including antibodies, small molecule TKIs, and
antibody drug conjugates);
10. The main organ functions are normal, which meets the following criteria:
1) The standard for blood routine examination should meet the requirement of: Hb ≥
90g/L (no blood transfusion or blood products within 14 days, no correction with
G-CSF or other hematopoietic stimulating factors); ANC≥1.5×109/L； PLT≥90×109/L； 2)
Biochemical tests must meet the following standards: TBiL≤1×ULN； ALT and AST ≤ 1.5 ×
ULN; ALP≤2.5×ULN； BUN and Cr ≤ 1.5 × ULN; 3) Cardiac ultrasound: Left ventricular
ejection fraction (LVEF) ≥ 50%; 11. The subjects voluntarily joined this study,
signed an informed consent form, had good compliance, and cooperated with follow-up.
Exclusion Criteria:
1. Individuals with a known history of allergies to the components of this medication
regimen;
2. Have other malignant tumors within the past 5 years prior to signing the informed
consent form (excluding non melanoma skin cancer or other tumors that have been
effectively treated, and malignant tumors that are considered cured);
3. Existence of brain metastases and/or cancerous meningitis;
4. Previously received allogeneic stem cell or parenchymal organ transplantation;
5. Past or current congenital or acquired immunodeficiency diseases;
6. Patients who are known or suspected to have a history of allergies to vediximab or
paclitaxel like drugs, or who have a history of hypersensitivity reactions to
chimeric or humanized antibodies or fusion proteins, or who are allergic to
excipients of the study drug;
7. Other significant clinical and laboratory abnormalities, which the researchers
believe will affect the safety evaluation, such as uncontrollable diabetes,
hypertension, cirrhosis, interstitial pneumonia, obstructive pulmonary disease,
chronic kidney disease, peripheral neuropathy of grade II or above (CTCAE V5.0),
thyroid dysfunction, heart failure of NYHA grade 3 or above, etc;
8. Severe infections that are active or poorly controlled clinically; Active
infections, including:
1. AIDS virus (HIV/2 antibody) positive;
2. Active hepatitis B (HBsAg positive or HBV DNA>2000IU/ml with abnormal liver
function);
3. Active hepatitis C (HCV antibody positive or HCV RNA ≥ 103 copies/ml with
abnormal liver function);
4. Active tuberculosis;
5. Other uncontrollable active infections (CTCAE V5.0>grade 2);
9. Severe heart disease or discomfort that cannot be treated;
10. Suffering from mental illness or substance abuse, unable to cooperate;
11. Simultaneously participating in other clinical trials;
12. The researchers believe that it is not suitable for the participants to be included.
Gender:
Male
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Tianjin Medical Unversity Second Hospital
Address:
City:
Tianjin
Zip:
300211
Country:
China
Status:
Recruiting
Contact:
Last name:
Haitao Wang
Phone:
+86-02288326610
Email:
peterrock2000@126.com
Contact backup:
Last name:
Lili Wang
Phone:
+86-13516108466
Email:
wangliliaigang@163.com
Investigator:
Last name:
Haitao Wang
Email:
Principal Investigator
Investigator:
Last name:
Lili Wang
Email:
Sub-Investigator
Investigator:
Last name:
Dingkun Hou
Email:
Sub-Investigator
Investigator:
Last name:
Jinhuan Wang
Email:
Sub-Investigator
Start date:
September 24, 2024
Completion date:
August 31, 2027
Lead sponsor:
Agency:
Tianjin Medical University Second Hospital
Agency class:
Other
Source:
Tianjin Medical University Second Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06663007
