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

Prior treatment

• 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);
• Previously received allogeneic stem cell or parenchymal organ transplantation;

Other illness

• Individuals with a known history of allergies to the components of this medication regimen;
• 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;
• 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;

Lab values

• 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;

Other

• Existence of brain metastases and/or cancerous meningitis;
• Simultaneously participating in other clinical trials;
• The researchers believe that it is not suitable for the participants to be included.

• 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:
  • 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.