RC48 Monotherapy or Combination With Envafolimab for CDK12 Alterations mCRPC With Standard Treatment Failure

NCT06663007 | Recruiting Phase 1

• 1 other identifier: RC48-mCRPC
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Prostate Cancer; CDK12 Gene Mutation

Outcome Measures

Primary Outcomes (1)

• 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.

  From treatment administration up to a maximum duration of 36 months

Secondary Outcomes (4)

• Objective Response Rate (ORR)

  Up to approximately 3 years

• Progression Free Survival(PFS)

  From treatment administration up to a maximum duration of 36 months

• Overall Survival(OS)

  From treatment administration up to a maximum duration of 36 months

• Percentage of Participants With Adverse Events (AEs)

  Up to approximately 3 years

Study Arms (2)

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.

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.

Drug: RC48

Interventions

RC48 DRUG

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.

Also known as: Disitamab Vedotin

Cohort A; Cohort B

Envafolimab DRUG

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.

Cohort A

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• 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:
• \) 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.

You may not qualify if:

• 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;
• 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;

Sponsors & Collaborators

• Tianjin Medical University Second Hospital: lead

Study Sites (1)

Tianjin Medical Unversity Second Hospital

Tianjin, Tianjin Municipality, 300211, China

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

disitamab vedotin; envafolimab

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Central Study Contacts

Haitao Wang, Ph.D

CONTACT

+86-022-88326385; peterrock2000@126.com

Jinhuan Wang, Ph.D

CONTACT

+86-022-88326610; wjhhappy2008@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: October 26, 2024
• First Posted: October 29, 2024
• Study Start: September 24, 2024
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): August 31, 2027
• Last Updated: October 29, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)