Short-course radiotherapy followed by penpulimab plus CAPEOX before surgery for microsatellite-stable locally advanced rectal cancer

Efficacy and Safety of Short-course Radiotherapy Sequential Penpulimab in Combination With CAPEOX in the Neoadjuvant Treatment of Microsatellite Stable Locally Advanced Rectal Cancer: a Single-centre, Single-arm, Phase 2 Study

This study tests whether short-course radiotherapy followed by the immunotherapy penpulimab combined with CAPEOX chemotherapy before surgery helps people with microsatellite-stable locally advanced rectal cancer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 55 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Ruijin Hospital (Academic / other)
• Drugs / interventions: Penpulimab, chemotherapy, immunotherapy
• Locations: 1 site (Shanghai, None Selected)
• Trial ID: NCT05576480 on ClinicalTrials.gov

What this trial studies

This is a phase 2 neoadjuvant trial that gives participants short-course radiotherapy (SCRT) followed by sequential penpulimab combined with CAPEOX chemotherapy prior to clinical restaging. After neoadjuvant therapy, patients undergo imaging and clinical reassessment to determine whether they can pursue a watch-and-wait approach or should proceed to radical (TME) surgery. The trial collects safety and efficacy data, including tumor response and surgical outcomes. The goal is to see if adding immunotherapy to SCRT and chemotherapy improves preoperative tumor control in MSS rectal cancer.

Who should consider this trial

Good fit: Adults aged 18–75 with MRI-confirmed mid-low, clinical stage II–III rectal adenocarcinoma that is microsatellite-stable (MSS), ECOG 0–1, no prior anti-tumor treatment, and no distant metastasis are the intended candidates.

Not a fit: Patients with MSI‑H/dMMR tumors, metastatic disease, poor performance status, or who require urgent surgery for complications are unlikely to benefit from this neoadjuvant approach.

Why it matters

Potential benefit: If successful, the regimen could increase preoperative tumor shrinkage and allow more patients to avoid or delay radical surgery through a watch-and-wait approach.

How similar studies have performed: Preclinical and small clinical studies suggest radiotherapy plus PD‑1 pathway blockade can boost anti-tumor immunity, but neoadjuvant PD‑1 approaches for MSS rectal cancer remain early and not yet proven in large trials.

Eligibility criteria

Inclusion Criteria:

* Informed consent
* 18 years \< age ≤ 75 years
* ECOG score is 0-1
* Patients with pathologically confirmed rectal adenocarcinoma, assessed by MRI as mid-low rectal cancer (the lower border of the tumor is less than 10cm from the anal verge), clinical stage II-III (cT1-2N1-2M0 or T3-4N0-2M0) according to the 8th Edition of AJCC Cancer Staging Manual
* Without emergency operation due to complication (bleeding, perforation or obstruction) caused by rectal cancer
* Microsatellite Instability detection using PCR capillary electrophoresis results in MSS
* Without any anti-tumor treatment
* No distant metastasis
* Have an imaging measurable or clinically assessable lesion
* Adequate organ and bone marrow function
* Female participants of childbearing age or male participants whose sexual partners are women of childbearing age are required to use effective contraception for the entire treatment period and for 6 months after the end of the treatment period

Exclusion Criteria:

* Recurrent rectal cancer
* Previous treatment with pelvic radiotherapy, rectal cancer surgery, chemotherapy, targeted therapy, immune checkpoint inhibitors (including but not limited to PD-1, PD-L1, CTLA-4)
* Proven inability to receive radiotherapy or allergy to the components of Penpulimab, capecitabine, oxaliplatin or their excipients
* Intestinal obstruction due to tumor (except in patients who have received a stoma)
* History of other primary malignancies, except for: malignancies in complete remission for at least 2 years prior to enrolment and not requiring other treatment during the study period; adequately treated non-melanoma skin cancer or lentigo maligna with no evidence of disease recurrence; adequately treated carcinoma in situ with no evidence of disease recurrence
* Active, known or suspected autoimmune disease or history of this disease within the previous 2 years (patients with vitiligo, psoriasis, alopecia or Graves' disease not requiring systemic treatment within the last 2 years, hypothyroidism requiring only thyroid hormone replacement therapy and type I diabetes requiring only insulin replacement therapy may be enrolled)
* Any of the following within 6 months prior to the start of treatment: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (New York Heart Association classification II-IV), cerebrovascular event, transient ischaemic attack, severe arrhythmia requiring drug treatment or symptomatic pulmonary embolism
* History of allogeneic organ transplantation and allogeneic haematopoietic stem cell transplantation
* Uncontrolled comorbidities including but not limited to: HIV infected; Serious infections that are active or poorly controlled clinically
* Pregnant woman or lactating woman
* Patients who have participated in another drug clinical trial within 4 weeks
* Suffering from acute or chronic active hepatitis B (HBsAg-positive and HBV DNA ≥ 200 IU/mL or ≥ 103 copies/mL) or acute or chronic active hepatitis C (HCV-positive and HCV RNA-positive)
* Received live attenuated vaccine within 4 weeks prior to enrolment or planned during the study period
* Major surgical procedure within 4 weeks prior to enrolment
* History of interstitial pneumonia
* Other acute or chronic diseases, mental disorders, or laboratory test abnormalities that may result in: increasing the risk associated with research participation or drug administration, or interfering with the interpretation of the results of the study, and the patient was classified as not eligible to participate in this study according to the judgment of the researchers

Where this trial is running

Shanghai, None Selected

• Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine — Shanghai, None Selected, China (Recruiting)

Study contacts

• Principal investigator: Ren Zhao, MD, PHD — Ruijin Hospitlal , Shanghai Jiaotong University School of Medicine
• Study coordinator: Ren Zhao, MD, PHD

Conditions Rectal Cancer; Locally Advanced; Immunotherapy; Neoadjuvant Treatment; Locally Advanced Rectal Cancer; Microsatellite stable