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Trial only in China, for HER-2 positive colorectal cancer.

Combination of an a targeted ACD (antibody-drug conjugate) and immunotherapy (anti PD-1)

Disitamab Vedotin: An antibody-drug conjugate (ADC) composed of a monoclonal antibody targeting human epidermal growth factor receptor 2 (EGFR2; HER2) and conjugated to an as of yet undisclosed cytotoxic agent, with potential antineoplastic activity. Approved in China.
Pembrolizumab: PD-1 checkpoint inhibitor (Keytruda®)
This trial is similar to NCT05493683, but this does not admit patients who already received immunotherapies.

有用链接

纳入标准

纳入标准

Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of histologically or cytologically confirmed unresectable metastatic CRC (KRAS, NRAS and BRAF wild type) with HER-2 expression (IHC2+ or IHC 3+) will be enrolled in this study.
东部合作肿瘤学组（ECOG）表现状态为 0 至 1。ECOG 评估应在首次服用研究干预药物前 7 天内进行。

Histologically and/or cytologically confirmed colorectal cancer, including:

（a) Unresectable metastatic colorectal adenocarcinoma (b)Evaluable or measurable HER2 expressing (IHC 3+ or IHC 2+) disease

Have received at least 2 prior treatments with systemic chemotherapy regimen until disease progression or intolerance; the patients with disease progression during or within 6 months after the adjuvant or neoadjuvant chemotherapy treatment should be recorded as first-line treatment; There is no restriction on whether the patient has received previous anti-HER2 treatment; for patients who have received previous anti-HER2 treatment, tissue re-biopsy should be done to confirm the expression of HER2 before enrollment; for patients who haven't received previous anti-HER2 treatment, HER2 status may refer to previous testing results from Tier 1 hospital.
Have measurable disease based on RECIST 1.1.
Have life expectancy of at least 3 months
Have adequate organ function as defined in the following table (Table 4).
Male participants: A male participant must agree to use a contraception as detailed in Appendix 2 of this protocol during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period.

Female participants: The participant (or legally acceptable representative if applicable) provides written informed consent for the trial. A female participant is eligible to participate if she is not pregnant (see Appendix 2), not breastfeeding, and at least one of the following conditions applies:

Not a woman of childbearing potential (WOCBP) as defined in Appendix 2 OR
A WOCBP who agrees to follow the contraceptive guidance in Appendix 2 during the treatment period and for at least
参与者（或法律上可接受的代表，如适用）提供试验知情同意书。

排除标准

排除标准：

Patients with any previous histological or hematological test showing mismatch repair gene deletion (dMMR), microsatellite instability (MSI-H)
Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-CTLA-4 or any cellular immunotherapy; has received prior therapy with other HER2-ADC tubulin inhibitors (such as T-DM1, RC-48, DS8201, etc.) or participated in similar clinical studies;
确诊患有免疫缺陷症，或在首次服用研究药物前 7 天内正在接受慢性全身类固醇治疗（剂量超过每天 10 毫克泼尼松当量）或任何其他形式的免疫抑制治疗。
患有活动性自身免疫性疾病，且在过去 2 年中需要接受系统治疗（即使用疾病调节剂、皮质类固醇或免疫抑制剂）。替代疗法（如甲状腺素、胰岛素或肾上腺或垂体功能不全的生理性皮质类固醇替代疗法等）不被视为系统治疗的一种形式，是允许的。
Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease, pulmonary fibrosis, acute lung disease, or uncontrolled systemic diseases (i.e., diabetes, hypertension).
Clinically uncontrollable diarrhea
Has a chronic or active infection requiring systemic antibacterial, antifungal, or antiviral therapy, including tuberculosis infection, etc. Patients with a history of active TB infection ≥1 year prior to screening should also be excluded, unless proof can be provided that appropriate treatment has been completed.
Has known active CNS metastases and/or carcinomatous meningitis.
Clinically significant pleural effusion, pericardial effusion or ascites requiring multiple drains within 2 weeks prior to treatment
Known second primary malignancy or additional malignancy within the past 5 years (Participants with basal cell carcinoma of the skin or carcinoma in situ of the cervix that have undergone potentially curative therapy are not excluded)
Uncontrolled diabetes or electrolyte disorder after the standard medical treatment
Has a known history of Human Immunodeficiency Virus (HIV) infection.

Concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV DNA) and Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection. Untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers with HBV DNA > 500 IU/mL and patients with positive HCV) RNA should be excluded.

Note: Hepatitis B and C screening tests are not required unless:

Known history of HBV and HCV infection
As mandated by local health authority
Has any major surgery≤28 days prior to the first dose
Prior allogeneic stem cell transplantation or prior organ transplantation.
Has severe hypersensitivity (≥Grade 3) to pembrolizumab and RC48-ADC and/or any of its excipients.
History of duodenal ulcer, ulcerative colitis, intestinal obstruction, or other conditions that may cause gastrointestinal bleeding or perforation as determined by researchers; history of intestinal perforation and fistula, but have not recovered after surgical treatment.
History of arterial thrombosis or deep vein thrombosis within 6 months before enrollment, or evidence or history of bleeding tendency within 2 months before enrollment, regardless of severity
History of Stroke or transient ischemic attack occurred within the first 12 months prior to enrollment.
Severe ulcer or fracture of skin, surgical site, wound site and mucosa is not completely healed.
Acute myocardial infarction, severe/unstable angina pectoris or coronary artery bypass grafting ≤ 6 months prior to study enrolment; New York Heart Association (NYHA) Functional Classification Grade II or greater congestive heart failure.
Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks, or immunotherapy (such as interleukin, interferon, thymosin), hormone therapy, targeted therapy or any research therapy within 14 days or 5 half-lives prior to start of study treatment [could consider shorter interval for kinase inhibitors or other short half-life drugs] prior to allocation.
Have received any Chinese herbal medicine or proprietary Chinese medicine for anticancer within 14 days prior to start of study treatment.
Patients whose toxic and side effects (due to previous anticancer treatment) have not recovered to baseline or stable level, unless AE may not with safety risks (such as hair loss, neuropathy and specific laboratory abnormalities).
Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.

Has an active or chronic infection requiring systemic therapy including tuberculosis infection, etc. History of active tuberculosis infection ≥1 year before screening should also be excluded, unless proof can be provided that appropriate treatment has been completed.

Note: No HIV testing is required unless mandated by local health authority.

Has a history or current evidence of any condition, therapy, or laboratory abnormality or other circumstance that might confound the results of the study, interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.
患有已知的精神疾病或药物滥用疾病，会影响配合试验要求。
Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
接受过异基因组织/实体器官移植。