Standard Second-line Therapy With ONgericimab and TOripalimab in pMMR/MSS Colorectal Cancer: a Single-arm Phase II Trial

NCT07106034 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: ONTOP
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

The ONTOP study is a prospective, single-arm, open-label phase II clinical trial. A total of 32 patients with advanced MSS/pMMR colorectal cancer who have failed first-line treatment will receive second-line standard treatment combined with Ongericimab and toripalimab. Among them, patients who received irinotecan-containing treatment in the first line will be administered the regimen of Ongericimab + toripalimab + bevacizumab + FOLFOX. Patients who received oxaliplatin-containing treatment in the first line will be administered the regimen of Ongericimab + toripalimab + bevacizumab + FOLFIRI. Treatment will continue until disease progression, initiation of new anti-tumor treatment, active request of the subject, or determination by the investigator that study drug administration needs to be terminated. The primary study endpoint is the objective response rate (ORR), and the secondary study endpoints include duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety, etc.

Conditions

Advanced Colorectal Cancer

Keywords

Toripalimab; Ongericimab; colorectal cancer; pMMR/MSS

Outcome Measures

Primary Outcomes (1)

• overall response rate

  overall response rate

  Two years

Secondary Outcomes (4)

• Disease control rates

  Two years

• Duration of Response

  Two years

• progression-free survival

  Two years

• overall survival

  Two years

Study Arms (1)

Second-line standard treatment combined with Ongericimab and toripalimab.

EXPERIMENTAL

If first line treatment with irinotecan-containing regimen: Ongrezicimab + Toripalimab + Bevacizumab + FOLFOX, Q2W If first line treatment with oxaliplatin-containing regimen: Ongrezicimab + Toripalimab + Bevacizumab + FOLFIRI, Q2W In addition, the period of 21 days after the first administration is defined as the DLT observation period.

Drug: Ongericimab + Toripalimab + Bevacizumab + FOLFOX; Drug: Ongericimab + Toripalimab + Bevacizumab + FOLFIRI

Interventions

Ongericimab + Toripalimab + Bevacizumab + FOLFOX DRUG

Ongericimab, Toripalimab, Bevacizumab, Oxaliplatin, Calcium folinate, 5-FU, Q2W

Second-line standard treatment combined with Ongericimab and toripalimab.

Ongericimab + Toripalimab + Bevacizumab + FOLFIRI DRUG

Ongericimab, Toripalimab, Bevacizumab, Irinotecan, Calcium folinate, 5-FU, Q2W

Second-line standard treatment combined with Ongericimab and toripalimab.

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects aged 18-75 years (inclusive of 18 and 75 years) at the time of signing the informed consent, regardless of gender.
• Histologically confirmed MSS/pMMR colorectal or rectal cancer, who have progressed on first-line fluoropyrimidine - based combination therapy (including progression during maintenance therapy). If FOLFOXIRI was received in the first - line, screening is not allowed; if progression occurred during neoadjuvant/adjuvant therapy or within 6 months after the last dose, it is considered first-line treatment failure, and the patient is eligible for enrollment.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• Predicted survival ≥ 12 weeks.
• At least 1 measurable lesion according to RECIST 1.1 evaluation criteria.
• Adequate organ function；
• Female or male subjects with childbearing potential must agree to have no childbearing plans within 6 months after the end of the last dose during the study period and be willing to take highly effective contraceptive measures together with their partners. For female subjects with childbearing potential, the serum pregnancy test must be negative within 7 days before the first dose, and they must be non - lactating.
• Be able to provide a signed informed consent form, including complying with the requirements and restrictions listed in the Informed Consent Form (ICF) and this protocol.

You may not qualify if:

• Presence of leptomeningeal metastasis; presence of active brain metastasis, defined as untreated and/or having clinical symptoms, or requiring glucocorticoids or antiepileptic drugs to control related symptoms. For those who have received local treatments such as surgery or radiotherapy, if the screening - period imaging assessment shows no evidence of progression for at least four weeks and symptoms disappear (except for residual signs or symptoms related to brain metastasis), no glucocorticoid treatment is needed for at least 2 weeks, and the acute toxicities related to previous treatments have recovered, enrollment is allowed.
• Presence of pleural effusion, peritoneal effusion, or pericardial effusion with clinical symptoms or requiring repeated management (such as puncture or drainage).
• History of immunodeficiency disorders, including positive detection of human immunodeficiency virus (HIV), or known allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
• History of severe cardiovascular diseases, including but not limited to: myocardial infarction within 6 months before the first study drug administration, severe/unstable angina pectoris, congestive heart failure (NYHA heart function class ≥2), severe supraventricular or ventricular arrhythmia, aortic aneurysm requiring surgical repair, any arterial thromboembolic event, grade 3 or above venous thromboembolic event, transient ischemic attack, cerebrovascular accident.
• Presence of abdominal or tracheoesophageal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess within 6 months before the first drug administration.
• Severe infection within 28 days before the first study drug administration (CTCAE 5.0 ≥ grade 2), such as severe pneumonia requiring hospitalization, bacteremia, infectious complications, etc.; active infection requiring intravenous anti-infection treatment or unexplained fever \> 38.5°C within 2 weeks before the first study drug administration (judged by the researcher; fever caused by the tumor in the subject can be enrolled).
• Presence of active tuberculosis, hepatitis B (hepatitis B surface antigen \[HBsAg\] positive and HBV DNA higher than the lower limit of detection of the research center), hepatitis C (HCV Ab positive and HCV RNA higher than the lower limit of detection of the research center).
• History of another primary malignant tumor, except for those who have received radical treatment before the first administration of the study intervention, have no known active disease (for more than 5 years), and have a low potential recurrence risk (such as skin basal cell carcinoma and cutaneous squamous cell carcinoma that have received curative treatment).
• The following situations do not allow screening:
• Screening period imaging shows that the tumor encircles important blood vessels or has obvious necrosis and cavity, and the researcher deems it may cause bleeding risk;
• Clinical signs or symptoms of intestinal obstruction and/or gastrointestinal obstruction within 6 months before the first drug administration, including incomplete obstruction related to the underlying disease;
• Presence of severe, unhealed, or ruptured wounds, active ulcers, or untreated fractures;
• Clinically significant hemoptysis (≥1/2 tea spoon) or tumor bleeding for any reason within 1 month before the first drug administration;
• Presence of poorly controlled hypertension (systolic blood pressure ≥150 mmHg and/or diastolic blood pressure \> 100 mmHg), or history of hypertensive emergency or hypertensive encephalopathy;
• Other situations judged by the researcher as unsuitable for receiving oral chemotherapy.

Sponsors & Collaborators

• Shanghai Pudong Hospital: lead
• Shanghai Junshi Bioscience Co., Ltd.: collaborator

Study Sites (1)

Shanghai Pudong Hospital

Shanghai, Shanghai Municipality, 201399, China

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

toripalimab; Bevacizumab; Folfox protocol

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Xuhui Bao, M.D., Ph.D.

CONTACT

862168035001; xuhui_bao@fudan.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2025
• First Posted: August 6, 2025
• Study Start: August 31, 2025
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2027
• Last Updated: August 12, 2025

Record last verified: 2025-08

Locations

CN (1)