Neoadjuvant Therapy for Locally Advanced Rectal Cancer

Penpulimab 200mg IV D1 Anlotinib 12mg P.O. QD D1-14 Radiation therapy 1.8-2Gy/50-55Gy

Chemotherapy:

Capecitabine 800mg/m2 P.O. BID D1-D14, or capecitabine plus oxaliplatin 130mg/m2. Every 21 days is 1 cycle In the above regimen, two cycles of targeted therapy (chemotherapy + immunotherapy + targeted therapy) are synchronized during radiotherapy; After the end of radiotherapy, two cycles of adjuvant chemo-immunotherapy (chemotherapy + immunotherapy) were continued.

• Anlotinib hydrochloride,Penpulimab (Drug), also known as FOCUS: Penpulimab 200mg IV D1 Anlotinib 12mg P.O. QD D1-14

Primary outcomes

• Pathologic complete response rate（pCR） [assessment 2-4 weeks after surgery]

Secondary outcomes

• R0 resection rate [assessment 2-4 weeks after surgery]
• Disease-free survival at 3 years [from enrollment to three years after surgery]
• OS at 3 years [from enrollment to three years later]
• RECIST1.1 Objective response rate as assessed [1-2 weeks before surgery]
• RECIST1.1 Disease control rate evaluated [1-2 weeks before surgery]

Sex: All, ages: 18 Years to 80 Years

Inclusion Criteria:

-Patient's age: 18 years old - 80 years old -

* Rectal cancer patients diagnosed with adenocarcinoma by pathological examination of primary biopsy
* Patients with no prior treatment, preoperative clinical stage: cT3-4N+M0 rectal cancer patients (AJCC 8th);
* Patients who agree to undergo radical surgical treatment and have no contraindications to surgery as judged by the surgeon;
* No other multiple primary cancers;
* At least 1 measurable or evaluable lesion according to the efficacy evaluation criteria for solid tumors version 1.1 (RECIST v1.1);
* Expected survival time≥ 3 months;
* A score of 0-1 based on the United States Eastern Cooperative Oncology Group Performance Status Score (ECOG PS score);
* The investigator plans to give PD-1 monoclonal antibody combined with chemotherapy treatment regimen after evaluation, and signs informed consent.

Exclusion Criteria:

* Active, known or suspected autoimmune disease;
* Known history of primary immunodeficiency;
* Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation;
* Pregnant or lactating female patients;
* Patients with intestinal obstruction, intestinal perforation, intestinal bleeding, etc., requiring emergency surgery;
* Uncontrolled intercurrent illness including but not limited to:
* People living with HIV (HIV antibody positive)
* Severe infections that are active or poorly clinically controlled
* Patients with active hepatitis
* Evidence of severe or uncontrolled systemic disease (e.g., severe psychiatric, neurological, epilepsy or dementia, unstable or incompensable respiratory, cardiovascular, hepatic or renal disease, uncontrolled hypertension \[i.e., greater than or equal to CTCAE grade 2 hypertension despite medication\]).
* Patients with active bleeding or new thrombotic disease, taking therapeutic dose of anticoagulant drugs or bleeding tendency, abnormal coagulation function (INR\>1.5×ULN, APTT\>1.5×ULN);
* Those who are currently undergoing clinical trials of other drugs;
* Other patients who are considered by the investigator to be unsuitable for inclusion.