Prostate CancerPhase 1/2NCT06663007
RC48 Monotherapy or Combination With Envafolimab for CDK12 Alterations mCRPC With Standard Treatment Failure
A Phase 1/2 study testing RC48 and Envafolimab in people with Prostate Cancer and CDK12 Gene Mutation, run by Tianjin Medical University Second Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer, CDK12 Gene Mutation
- What is being tested?
- RC48 and Envafolimab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 1 siteChina
- Study dates
- 24 Sep 2024to 31 Aug 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
- Patients aged ≥ 18 years old;
- 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+;
- Carrying CDK12 mutation combined with ERBB amplification (NGS or FISH) or HER2 IHC (1+, 2+, 3+);
- According to the RECIST solid tumor efficacy evaluation criteria, there must be at least one measurable lesion;
- ECOG PS: 0-2 points;
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- Expected survival period is not less than 12 weeks;
- 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);
- Have not used HER2 targeted drugs (including antibodies, small molecule TKIs, and antibody drug conjugates);
- 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.
Who cannot join
- Individuals with a known history of allergies to the components of this medication regimen;
- 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);
- Existence of brain metastases and/or cancerous meningitis;
- Previously received allogeneic stem cell or parenchymal organ transplantation;
- Past or current congenital or acquired immunodeficiency diseases;
- 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;
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- 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;
- Severe infections that are active or poorly controlled clinically; Active infections, including:
- AIDS virus (HIV/2 antibody) positive;
- Active hepatitis B (HBsAg positive or HBV DNA>2000IU/ml with abnormal liver function);
- Active hepatitis C (HCV antibody positive or HCV RNA ≥ 103 copies/ml with abnormal liver function);
- Active tuberculosis;
- Other uncontrollable active infections (CTCAE V5.0>grade 2);
- Severe heart disease or discomfort that cannot be treated;
- Suffering from mental illness or substance abuse, unable to cooperate;
- Simultaneously participating in other clinical trials;
- The researchers believe that it is not suitable for the participants to be included.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Tianjin Medical Unversity Second Hospital
Tianjin, Tianjin Municipality, 300211
Haitao Wang, +86-02288326610, peterrock2000@126.com
Lili Wang, +86-13516108466, wangliliaigang@163.com
About this study
Official title: Prospective, Single Arm, Multi Cohort Clinical Study of Disitamab Vedotin(RC48) Monotherapy or Combination With Envafolimab for Second-line Treatment of CDK12 Alterations Metastatic Castration Resistant Prostate Cancer With Standard Treatment Failure
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.
Read the 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.
- Conditions
- Prostate Cancer, CDK12 Gene Mutation
- Being tested
- RC48, Envafolimab
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RC48Drug
Also called Disitamab Vedotin
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.
EnvafolimabDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Cohort A | Experimental | During the treatment phase of patients in cohort A (excluding CDK12 alterations from mutation spectrum features in cohort B), subjects received intravenous infusion of Disitamab Vedotin(RC48) (2.0 mg/kg) every 2 weeks, in combination with subcutaneous injection of Envafolimab (400 mg) every 3 weeks, until disease progression or death occurred. Receives: Drug: RC48; Drug: Envafolimab |
| Cohort B | Experimental | During the treatment phase, subjects in cohort B (CDK12 alterations combined with 11q13 co-amplification, MDM2/4 amplification, FGFRs amplification and other chromosomal unstable mutation profiles) received intravenous infusion of Disitamab Vedotin(RC48) (2.0 mg/kg) every 2 weeks until disease progression or death occurred. Receives: Drug: RC48 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Prostate Specific Antigen (PSA) ≥50% Response Rate (PSA50)
Will assess PSA decline of ≥50% from baseline (PSA50), using the Prostate Cancer Working Group 3 (PCWG3) criteria.
Measured: From treatment administration up to a maximum duration of 36 months
Secondary outcomes (4)
Objective Response Rate (ORR)
Objective Response Rate (ORR) assessed according to the evaluation criteria for the efficacy of solid tumors (RECIST v1.1).
Measured: Up to approximately 3 years
Progression Free Survival(PFS)
The time from the beginning of the patient's treatment to the disease progression or death for any reason.Based on RECIST criteria v1.1
Measured: From treatment administration up to a maximum duration of 36 months
Overall Survival(OS)
Time from start of treatment to death due to any cause.
Measured: From treatment administration up to a maximum duration of 36 months
Percentage of Participants With Adverse Events (AEs)
Number of participants with adverse effects of treatment. Frequency and severity of adverse effects of treatment as assessed by NCI CTCAE v5.0
Measured: Up to approximately 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2024
- Study start24 Sep 2024
- Primary completion31 May 2027 (estimated)
- Study completion31 Aug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- 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.
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 72 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tianjin Medical University Second Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06663007
- Sponsor's protocol ID
- RC48-mCRPC
- Status last verified
- Aug 2024
- First submitted
- 26 Oct 2024
- Last updated
- 29 Oct 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective, Single Arm, Multi Cohort Clinical Study of Disitamab Vedotin(RC48) Monotherapy or Combination With Envafolimab for Second-line Treatment of CDK12 Alterations Metastatic Castration Resistant Prostate Cancer With Standard Treatment Failure
- ClinicalTrials.gov ID
- NCT06663007
- Acronym / sponsor ID
- RC48-mCRPC
- Conditions
- Prostate Cancer, CDK12 Gene Mutation
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 72 participants (estimated)
- Lead sponsor
- Tianjin Medical University Second HospitalUniversity, hospital or other
- Study start
- 24 Sep 2024 (actual)
- Primary completion
- 31 May 2027 (estimated)
- Study completion
- 31 Aug 2027 (estimated)
- First posted
- 29 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- Single blind (investigator)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Cohort A | Experimental | Drug: RC48, Drug: EnvafolimabDuring the treatment phase of patients in cohort A (excluding CDK12 alterations from mutation spectrum features in cohort B), subjects received intravenous infusion of Disitamab Vedotin(RC48) (2.0 mg/kg) every 2 weeks, in combination with subcutaneous injection of Envafolimab (400 mg) every 3 weeks, until disease progression or death occurred. |
| Cohort B | Experimental | Drug: RC48During the treatment phase, subjects in cohort B (CDK12 alterations combined with 11q13 co-amplification, MDM2/4 amplification, FGFRs amplification and other chromosomal unstable mutation profiles) received intravenous infusion of Disitamab Vedotin(RC48) (2.0 mg/kg) every 2 weeks until disease progression or death occurred. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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;
- Patients aged ≥ 18 years old;
- 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+;
- Carrying CDK12 mutation combined with ERBB amplification (NGS or FISH) or HER2 IHC (1+, 2+, 3+);
- According to the RECIST solid tumor efficacy evaluation criteria, there must be at least one measurable lesion;
Key exclusion criteria (17 listed)
- Individuals with a known history of allergies to the components of this medication regimen;
- 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);
- Existence of brain metastases and/or cancerous meningitis;
- Previously received allogeneic stem cell or parenchymal organ transplantation;
- Past or current congenital or acquired immunodeficiency diseases;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RC48Also: Disitamab VedotinDuring 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. | Drug | Cohort A, Cohort B |
| EnvafolimabDuring 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. | Drug | Cohort A |
Primary outcome
Prostate Specific Antigen (PSA) ≥50% Response Rate (PSA50)
Time frame: From treatment administration up to a maximum duration of 36 months
Will assess PSA decline of ≥50% from baseline (PSA50), using the Prostate Cancer Working Group 3 (PCWG3) criteria.
4 secondary outcomes
Objective Response Rate (ORR)
Time frame: Up to approximately 3 years
Progression Free Survival(PFS)
Time frame: From treatment administration up to a maximum duration of 36 months
Overall Survival(OS)
Time frame: From treatment administration up to a maximum duration of 36 months
Percentage of Participants With Adverse Events (AEs)
Time frame: Up to approximately 3 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing RC48 and Envafolimab in people with Prostate Cancer and CDK12 Gene Mutation, run by Tianjin Medical University Second Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 29 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Haitao Wang, Ph.D (+86-022-88326385, peterrock2000@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Prostate Specific Antigen (PSA) ≥50% Response Rate (PSA50) (time frame: From treatment administration up to a maximum duration of 36 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Oct 2024.