Combination of AK104 and Neoadjuvant Chemoradiotherapy in pMMR/MSS Locally Advanced Rectal Cancer
Study Details
Study Description
Brief Summary
This is an open-label, single-arm study to investigate the efficacy and safety of AK104 (an Anti-PD1 and Anti-CTLA4 Bispecific Antibody) and neoadjuvant chemoradiotherapy in patients with pMMR/MSS locally advanced rectal cancer.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
The study evaluates the addition of AK104(an Anti-PD1 and Anti-CTLA4 Bispecific Antibody) in neoadjuvant chemoradiotherapy in proficient Mismatch Repair (pMMR) /Microsatellite Stable (MSS) locally advanced rectal cancer (LARC). A total of 33 pMMR/MSS LARC patients will receive long-course chemoradiotherapy plus 2 cycles of AK104, followed by another 3 cycles of AK104, finally received clinical routine manage. The tumor response to treatment, adverse effects and long-term prognosis will be analyzed.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment Arm A total of 33 pMMR/MSS LARC patients will receive long-course chemoradiotherapy plus 2 cycles of AK104, followed by another 3 cycles of AK104, finally received clinical routine manage. |
Drug: AK104
During neo-CRT: 2 cycles of AK104, 10mg/kg d1 q3w. After neo-CRT: 3 cycles of AK104, 10mg/kg d1 q3w.
Other Names:
Drug: Capecitabine
During neo-CRT: 825mg/m2 bid Monday-Friday per week
Radiation: Neoadjuvant Radiotherapy
IMRT DT: 50Gy/25Fx
|
Outcome Measures
Primary Outcome Measures
- Complete response (CR) rate [an average of 6 months.]
Rate of complete response (CR), including pathologic complete response (pCR) and clinical complete response (cCR).
Secondary Outcome Measures
- Adverse effects [From date of randomization until the date of death from any cause, assessed up to 5 years]
Adverse effects according to CTCAE 5.0
- Rate of Major pathologic response and tumor regression grade distribution [an average of 1 year.]
Rate of Major pathologic response and tumor regression grade distribution
- Rate of surgical complications [The surgery was scheduled 2-4 weeks after the end of neoadjuvant therapy. And the surgical complications were assessed up to 1 year from the surgery.]
Rate of surgical complications, such as intraoperative hemorrhage, anastomotic leakage, intestinal obstruction, etc.
- Disease free survival [From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.]
3 year disease free survival rate
- Local recurrence free survival [From date of randomization until the date of first documented pelvic failure, assessed up to 36 months.]
3 year local recurrence free survival rate
- Overall survival [From date of randomization until the date of death from any cause, assessed up to 60 months.]
5 year overall survival rate
- Long-term anal function [1.5 year after diagnosis]
Long-term anal function was evaluated using the Wexner Continence Grading Scale ,the score being calculated after the patients' completion of a daily defecatory questionnaire. Range is from 0 (normal continence) to 20 (maximum incontinence with maximum disturbance of lifestyle)
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Age 18-75
-
ECOG 0-1
-
Rectal adenocarcinoma
-
cT3-4aNany or cT1-4aN+
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No distant metastasis
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Location ≤15 cm from the anal verge
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the MSI status is MSS and pMMR
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Sufficient bone marrow, kidney and liver function
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No previous surgery of the rectum, no previous chemotherapy, no previous pelvic radiation, no previous biotherapy, no immunotherapy
Exclusion Criteria:
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bowel obstruction
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Distant metastasis
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Severe arrhythmia, cardiac dysfunction (NYHA grade III or IV )
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Uncontrollable severe hypertesion
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Active severe infection
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Cachexia, organ dysfunction
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Previous pelvic radiotherapy or chemotherapy
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Multiple primary cancers
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Epileptic seizures
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Malignant history within 5 years, except cervical carcinoma in situ or cutaneous basal cell carcinoma
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Persons deprived of liberty or under guardianship
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Impossibility for compliance to follow-up
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Certain or suspicious allergy to research drug
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Pregnant or breast-feeding woman
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Sun Yat-sen University Cancer Center | Guangzhou | Guangdong | China | 510060 |
Sponsors and Collaborators
- Sun Yat-sen University
- Akeso
- Haplox Biotechnology Co., Ltd.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- B2022-766-01