Phase 2 Randomized Study of Neoadjuvant Dostarlimab Plus CAPEOX Versus CAPEOX in T4N0 or Stage III MMRp/MSS Colon Cancer Patients
- Trial ID
- 2024-513441-36-00
- Protocol
- 222892
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this Phase 2, open-label, randomized study is to assess the **efficacy** and **safety** of neoadjuvant dostarlimab in combination with CAPEOX compared to CAPEOX alone in participants with previously untreated T4N0 or Stage III MMRp/MSS colon cancer. This evaluation is clinically relevant as it aims to determine whether the addition of dostarlimab can enhance treatment outcomes and maintain an acceptable safety profile in this patient population.
Secondary objectives include:
- Assessing the **feasibility** of neoadjuvant dostarlimab in combination with CAPEOX versus CAPEOX alone.
- Further evaluating the **efficacy** of the combination therapy in the specified patient group.
Participants
The clinical trial involves a total of **17 participants** diagnosed with **colon cancer**, specifically MMRp/MSS colon cancer, at stages T4N0 or Stage III. The study population includes both male and female subjects, aged 18 years and older, who have not received prior treatment for their condition. Participants were selected based on their ability to provide informed consent and their compliance with the study's requirements. They must have resectable colon adenocarcinoma and demonstrate adequate organ function, as well as an Eastern Cooperative Oncology Group Performance Status (ECOG-PS) of 0 or 1. The trial does not include vulnerable populations. Participants are required to adhere to specific contraceptive measures to prevent pregnancy during the study. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The selection criteria ensure that participants have a confirmed diagnosis and are capable of complying with the study protocol.
Plans and Procedures
The clinical trial is a **Phase 2**, open-label, randomized study designed to evaluate the efficacy and safety of neoadjuvant **dostarlimab** in combination with CAPEOX compared to CAPEOX alone in participants with previously untreated T4N0 or Stage III MMRp/MSS colon cancer. The trial employs a randomized, controlled design to ensure unbiased results, with participants being randomly assigned to either the experimental group receiving dostarlimab plus CAPEOX or the control group receiving only CAPEOX. The study is expected to span approximately four years, with an estimated recruitment start date in December 2024 and an anticipated end date in September 2028.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on specific criteria, such as age, diagnosis of colon adenocarcinoma, and tumor characteristics. Following the screening, eligible participants will be enrolled and randomized into one of the study arms. Throughout the trial, participants will attend regular follow-up visits to monitor treatment response, assess safety, and manage any adverse events. These visits will include clinical assessments, laboratory tests, and imaging studies as required by the protocol. The end-of-study visit will occur after the completion of the treatment period, where final evaluations will be conducted to assess the primary and secondary endpoints, including the proportion of participants with major pathological response and the frequency of treatment-emergent adverse events.
The expected length of participant involvement in the study is up to 12 months, corresponding to the maximum treatment period. However, certain conditions may lead to early termination from the study, such as disease progression precluding surgery, treatment-related toxicity, or withdrawal of consent by the participant. The trial aims to provide valuable insights into the potential benefits of combining dostarlimab with CAPEOX in treating MMRp/MSS colon cancer, contributing to the advancement of therapeutic strategies for this condition.
Treatment
The clinical trial involves the administration of **dostarlimab**, marketed under the name JEMPERLI, which is a 500 mg concentrate for solution for infusion. This experimental medication is administered intravenously. The dosing schedule allows for a maximum daily dose of 500 mg, with a total maximum dose of 2000 mg over a treatment period of up to 12 months. Dostarlimab is a protein-based therapeutic agent, and its administration requires the use of a closed system transfer device to ensure compatibility and safety during infusion.
In addition to dostarlimab, the trial includes the administration of **capecitabine**, available in various formulations such as Capecitabina Zentiva 500 mg film-coated tablets and CAPECITABINE ZENTIVA 150 mg film-coated tablets. Capecitabine is administered orally, with a maximum daily dose of 2000 mg/m² and a total maximum dose of 112000 mg/m² over a 12-month period. This chemical-based agent is part of the standard-of-care therapy and is used in combination with other treatments in the study.
Another component of the trial is **oxaliplatin**, provided as Oxaliplatin AqVida 5 mg/ml concentrate for solution for infusion. This medication is administered intravenously, with a maximum daily dose of 130 mg/m² and a total maximum dose of 520 mg/m² over the course of 12 months. Oxaliplatin is a platinum-based chemotherapy agent and is used as a comparator treatment in the study.
Participant compliance with the dosing schedules is monitored throughout the trial to ensure adherence to the treatment regimen. The trial aims to evaluate the efficacy and safety of the combination of dostarlimab with CAPEOX (capecitabine and oxaliplatin) compared to CAPEOX alone in participants with T4N0 or Stage III MMRp/MSS colon cancer.
Efficacy
The efficacy of the clinical trial will be assessed by evaluating the primary and secondary endpoints. The primary endpoints include the proportion of participants with a major pathological response, determined by local assessment with protocol-specific training and methods, defined as having ≤10% residual viable tumor (**RVT**). Additionally, the frequency and severity of treatment-emergent adverse events (AEs), serious adverse events (SAEs), immune-mediated adverse events (imAEs), and AEs leading to death or discontinuation of the study intervention will be monitored.
Secondary endpoints will focus on the proportion of participants for whom primary tumor resection is not excluded due to disease progression precluding surgery or treatment-related toxicity that renders the participant unsuitable for surgery. Furthermore, the pathological response will be categorized into complete pathologic response (cPR) with 0% RVT, major pathological response excluding cPR (>0% & ≤10% RVT), partial pathologic response (>10% & ≤50% RVT), and negligible pathologic response (>50% RVT). These assessments will be conducted through local evaluations, ensuring adherence to the protocol's specific guidelines and methodologies.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Is at least 18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place) at the time of signing the ICF.
- Has untreated pathologically confirmed colon adenocarcinoma.
- Has resectable colon adenocarcinoma defined as clinically T4N0 or Stage III.
- Has a tumor demonstrating the presence of either: a. MMR status: MMR status must be assessed by IHC for MMR protein expression (MLH1, MSH2, MSH6, PMS2) where all proteins are present indicates MMRp; MMR status may be determined local laboratory; or b. MSS or MSI-L phenotype as determined by PCR or by tissue NGS, determined by local laboratory.
- Provides fresh tumor tissue obtained during either the pre-screening or screening period via colonoscopy performed per procedure manual. Tissue biopsy is required.
- Is willing to use adequate contraception male and/or female participants. − Contraceptive use by male and/or female participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. − Male participants: Male participants are eligible to participate if they agree to the following during the study intervention period and for at least 180 days, after the last dose of chemotherapy, or longer if required by local label or regulations. − Refrain from donating sperm PLUS, either: − Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent. OR − Must agree to use contraception/barrier as detailed below: o Agree to use a male condom and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak when having sexual intercourse with a WOCBP who is not currently pregnant. o Agree to use a male condom when engaging in any activity that allows for passage of ejaculate to another person. − Female participants: (ALL female participants regardless of randomization): • A female participant is eligible to participate if she is not pregnant or breastfeeding, and 1 of the following conditions applies: − Is a WONCBP as defined in the protocol OR − Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), preferably with low user dependency, as described in the protocol, during the study intervention period and for at least 180 days after the last dose of NAT. − The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated) in relationship to the first dose of study intervention. − A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study intervention. − If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. − Additional requirements for pregnancy testing during and after study intervention will be provided in the protocol. • The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
- Is capable of giving signed informed consent as described in protocol, including compliance with the requirements and restrictions listed in the ICF and in this protocol.
- Has an ECOG-PS of 0 or 1.
- Has adequate organ function as defined in protocol.
Exclusion Criteria
- Has distant metastatic disease.
- Has received prior medical therapy (chemotherapy, immunotherapy, biologic, or targeted therapy), radiation therapy or surgery for management of colon cancer.
- Has a tumor that, in the investigator’s judgment is causing symptomatic bowel obstruction or otherwise requires or required urgent/emergent surgery.
- Has, in the investigator’s opinion, a tumor that is not amenable to surgery or has any other contraindication to surgery.
- Has a known additional malignancy that progressed or required active treatment within the past 2 years. Exceptions include adequately treated superficial nonmelanoma skin cancers, superficial bladder cancers, and other in situ cancers.
- Is immunocompromised in the opinion of the investigator.
- Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
- Has experienced any of the following with prior immunotherapy: any imAE ≥ Grade 3, immune-mediated severe neurologic events of any-grade (e.g., myasthenic syndrome/myasthenia gravis, encephalitis, Guillain-Barré Syndrome, or transverse myelitis), exfoliative dermatitis of any grade (SJS, TEN, or DRESS syndrome), or myocarditis of any grade. Non-clinically significant laboratory abnormalities are not exclusionary.
- Has undergone any major surgical procedure, open biopsy, or experienced significant traumatic injury, or has not recovered from such within 35 days prior to randomization.
- Has any history of interstitial lung disease or immune-related pneumonitis.
- Has a history or current evidence of any medical condition, therapy, or laboratory abnormality that might confound the study results, interfere with their participation for the full duration of the study intervention, or indicate it is not in the best interest of the participant to participate, in the opinion of the investigator.
- Has a history of allogenic stem cell or organ transplantation.
- Has known complete dihydropyrimidine hydrogenase (DPD) deficiency.
- Has a history of congenital long QT syndrome.
- Is considered, in investigator’s opinion, a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease, or active infection requiring systemic therapy. Specific examples include but are not limited to uncontrolled major seizure disorder; unstable spinal cord compression; superior vena cava syndrome; or any psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study (including obtaining informed consent).
- Has a history of or evidence of cardiac abnormalities such as serious, uncontrolled cardiac arrhythmia or clinically significant ECG abnormalities within the 6 months prior to randomization, including: − Second degree (Type II) or third-degree atrioventricular block. − Cardiomyopathy, myocarditis, myocardial infraction, acute coronary syndromes (including unstable angina pectoris), coronary angioplasty, stenting, or bypass grafting. − Symptomatic pericarditis.
- Has an ALT value >2.5x ULN.
- Has a total bilirubin value >1.5x ULN.
- Has cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal/gastric varices, or persistent jaundice.
- Has documented presence of HBsAg at screening or within 3 months prior to thefirst dose of study intervention. Participants with a negative HBsAg and positive HBcAb result are eligible only if HBV DNA is negative.
- Has a positive HCV antibody test result at screening or within 3 months prior to thefirst dose of study intervention.
- Has a positive HCV RNA test result at screening or within 3 months prior to the first dose of study intervention.
- Has received treatment with an investigational agent within [4 weeks] of the firstdose of study intervention.
- Is receiving immunosuppressive medication.
- Has received systemic corticosteroids (>10 mg daily prednisone or equivalent) within 7 days of first dose of study intervention. Use of inhaled steroids, local injection of steroids, topical steroids, and steroidal eye drops are allowed.
- Has previously received any therapies for their colon cancer.
- Has received any live vaccine within 30 days of randomization. Vaccination against COVID-19 using vaccines that are authorized via the appropriate regulatory mechanisms (e.g., Emergency Use Authorization, Conditional Marketing Authorization, or Marketing Authorization Application) are not exclusionary.
- Is currently enrolled or has participated in any other clinical study involving an investigational study intervention or any other type of interventional medical research within 35 days, or less than 5 times the half-life of the most recent therapy prior to study Day 1, whichever is shorter.
- Has a known HIV infection AND meets at least 1 of the following criteria: a. Has documented evidence of plasma HIV-1 RNA ³50 c/mL within 3 months prior to or at screening. In the 3 to 12 months prior to screening, plasma HIV-1 RNA levels consistently <50 c/mL are required for enrolment; if multiple instances of plasma HIV-1 RNA values ³50 c/mL occurred in the 3 to 12 months prior to screening, the participant is not eligible for enrolment unless, per the investigator’s assessment, the elevations were neither persistent nor associated with antiretroviral resistance; OR b. Has not had CD4 cell counts measured in the past 12 months (i.e., at least 2 separate measurements taken a minimum of 28 days apart, 1 of which must be conducted at screening); OR c. Has had any CD4 cell count values ≤200 cells/mm3 in the past 12 months; OR d. Has had 1 or more changes in their combination antiretroviral therapy regimen (except for switches as allowed per details provided in (Section 10.9 [Appendix 9] or has received an antiretroviral therapy regimen that is inconsistent with locally recommended guidelines during the 3 months prior to screening; OR e. Has received treatment with an HIV-1 immunotherapeutic vaccine within 90 days of screening.
- Is pregnant or breastfeeding
- Is unable to adhere to the protocol-defined SoA, including requirements for the Safety and Survival Follow-up Period of the study.
- Has a history of severe allergic and/or anaphylactic reactions to chimeric, human, or humanized antibodies, fusion proteins, or known allergies to dostarlimab, or its excipients, or any components of CAPEOX.
- Has any other condition that would exclude the participant from chemotherapy with CAPEOX.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Recruiting | 05 Dec 2024 | 119 |
 Italy | Recruiting | 05 Dec 2024 | 36 |
 Spain | Recruiting | 05 Dec 2024 | 15 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
CAPECITABINE ZENTIVA 150 mg, comprimé pelliculé | Test | COMPRIMÉ PELLICULÉ | ORAL | 2000.0 | 12 | PRD6662711 |
Capecitabine Accord 150 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL | 2000.0 | 12 | PRD1614129 |
Oxaliplatin Bendalis 5 mg/ml Konzentrat zur Herstellung einer Infusionslösung | Test | KONZENTRAT ZUR HERSTELLUNG EINER INFUSIONSLÖSUNG | INTRAVENOUS | 130.00 | 12 | PRD6402145 |
Oxaliplatin AqVida 5 mg/ml Konzentrat zur Herstellung einer Infusionslösung | Test | KONZENTRAT ZUR HERSTELLUNG EINER INFUSIONSLÖSUNG | INTRAVENOUS | 130 | 12 | PRD1874310 |
Capecitabin "Zentiva", filmovertrukne tabletter | Test | FILMOVERTRUKNE TABLETTER | ORAL | 2000 | 12 | PRD9851601 |
Capecitabina Zentiva 500 mg compresse rivestite con film. | Test | COMPRESSE RIVESTITE CON FILM | ORAL | 2000 | 12 | PRD6664413 |
Capecitabine Zentiva 150 mg filmdragerade tabletter | Test | FILMDRAGERADE TABLETTER | ORAL | 2000 | 12 | PRD9485796 |
Capecitabin "Zentiva", filmovertrukne tabletter | Test | FILMOVERTRUKNE TABLETTER | ORAL | 2000 | 12 | PRD9851619 |
CAPECITABINE ZENTIVA 150 mg, comprimé pelliculé | Test | COMPRIMÉ PELLICULÉ | ORAL | 2000 | 12 | PRD6662706 |
JEMPERLI 500 mg concentrate for solution for infusion | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS | 500 | 12 | PRD8877508 |