Trial Outcomes & Findings for Durvalumab for MSI-H or POLE Mutated Metastatic Colorectal Cancer (NCT NCT03435107)

Last Updated: 2024-10-15

Results Overview

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR): Disappearance of all target lesions Partial Response (PR):\>=30% decrease in the sum of the longest diameter of target lesions Overall Response (OR) = CR + PR

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

33 participants

Primary outcome timeframe

First measurement should be at 8weeks from first administration.After first measurement, it should be followed up at every 8weeks until date of progression disease or date of death from any cause, whichever came first, assessed up to 46months..

Results posted on

2024-10-15

Participant Flow

Participant milestones

Participant milestones
Measure	Durvalumab The mismatch repair deficient or microsatellite instable, or POLE mutated metastatic colorectal cancer patients who were refractory to fluoropyrimidines, irinotecan and oxaliplatin with or without targeted agents will be accrued. After checking the eligibility for the study entry, patients will be entered into the study treatment with durvalumab monotherapy. Durvalumab: Study treatment consists of durvalumab 1500 mg Q4W for patients \> 30 kg, and will be repeated every 4 weeks. For patients ≤ 30 kg, weight based dosing of 20 mg/kg durvalumab Q4W will be used. Response evaluation will be performed every 8 weeks (± 1-week window period). Treatment will be continued until disease progression, unacceptable adverse events or the patient's refusal. Treatment through progression is at the investigator's discretion, and the investigator should ensure that patients do not have any significant, unacceptable, or irreversible toxicity that indicate that continuing treatment will not further benefit the patient. The Investigator should ensure that patients still meet all of the inclusion criteria and none of the exclusion criteria for this study.
Overall Study STARTED	33
Overall Study COMPLETED	32
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Durvalumab for MSI-H or POLE Mutated Metastatic Colorectal Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Durvalumab n=33 Participants The mismatch repair deficient or microsatellite instable, or POLE mutated metastatic colorectal cancer patients who were refractory to fluoropyrimidines, irinotecan and oxaliplatin with or without targeted agents will be accrued. After checking the eligibility for the study entry, patients will be entered into the study treatment with durvalumab monotherapy. Durvalumab: Study treatment consists of durvalumab 1500 mg Q4W for patients \> 30 kg, and will be repeated every 4 weeks. For patients ≤ 30 kg, weight based dosing of 20 mg/kg durvalumab Q4W will be used. Response evaluation will be performed every 8 weeks (± 1-week window period). Treatment will be continued until disease progression, unacceptable adverse events or the patient's refusal. Treatment through progression is at the investigator's discretion, and the investigator should ensure that patients do not have any significant, unacceptable, or irreversible toxicity that indicate that continuing treatment will not further benefit the patient. The Investigator should ensure that patients still meet all of the inclusion criteria and none of the exclusion criteria for this study.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	22 Participants n=5 Participants
Age, Categorical >=65 years	11 Participants n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants
Sex: Female, Male Male	27 Participants n=5 Participants
Race/Ethnicity, Customized Asian	33 Participants n=5 Participants
Region of Enrollment South Korea	33 participants n=5 Participants
Primary tumor Right colon	21 Participants n=5 Participants
Primary tumor Left colon	9 Participants n=5 Participants
Primary tumor Rectum	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: First measurement should be at 8weeks from first administration.After first measurement, it should be followed up at every 8weeks until date of progression disease or date of death from any cause, whichever came first, assessed up to 46months..

Outcome measures

Outcome measures
Measure	Durvalumab n=33 Participants The mismatch repair deficient or microsatellite instable, or POLE mutated metastatic colorectal cancer patients who were refractory to fluoropyrimidines, irinotecan and oxaliplatin with or without targeted agents will be accrued. After checking the eligibility for the study entry, patients will be entered into the study treatment with durvalumab monotherapy. Durvalumab: Study treatment consists of durvalumab 1500 mg Q4W for patients \> 30 kg, and will be repeated every 4 weeks. For patients ≤ 30 kg, weight based dosing of 20 mg/kg durvalumab Q4W will be used. Response evaluation will be performed every 8 weeks (± 1-week window period). Treatment will be continued until disease progression, unacceptable adverse events or the patient's refusal. Treatment through progression is at the investigator's discretion, and the investigator should ensure that patients do not have any significant, unacceptable, or irreversible toxicity that indicate that continuing treatment will not further benefit the patient. The Investigator should ensure that patients still meet all of the inclusion criteria and none of the exclusion criteria for this study.
Objective Response Rates (RECIST 1.1)	42.4 Percentage of participants Interval 25.5 to 60.8

SECONDARY outcome

Timeframe: Through study completion, an average of 2 years and 3months

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Disease control rate (DCR); The percentage of patients with the best overall response of complete response (CR), partial response (PR), or stable disease (SD) sustained for at least 6 weeks.

Outcome measures

Outcome measures
Measure	Durvalumab n=33 Participants The mismatch repair deficient or microsatellite instable, or POLE mutated metastatic colorectal cancer patients who were refractory to fluoropyrimidines, irinotecan and oxaliplatin with or without targeted agents will be accrued. After checking the eligibility for the study entry, patients will be entered into the study treatment with durvalumab monotherapy. Durvalumab: Study treatment consists of durvalumab 1500 mg Q4W for patients \> 30 kg, and will be repeated every 4 weeks. For patients ≤ 30 kg, weight based dosing of 20 mg/kg durvalumab Q4W will be used. Response evaluation will be performed every 8 weeks (± 1-week window period). Treatment will be continued until disease progression, unacceptable adverse events or the patient's refusal. Treatment through progression is at the investigator's discretion, and the investigator should ensure that patients do not have any significant, unacceptable, or irreversible toxicity that indicate that continuing treatment will not further benefit the patient. The Investigator should ensure that patients still meet all of the inclusion criteria and none of the exclusion criteria for this study.
Disease Control Rate (DCR)	66.7 Percentage of participants Interval 48.2 to 82.0

Adverse Events

Durvalumab

Serious events: 13 serious events

Other events: 28 other events

Deaths: 15 deaths

Serious adverse events

Serious adverse events
Measure	Durvalumab n=33 participants at risk The mismatch repair deficient or microsatellite instable, or POLE mutated metastatic colorectal cancer patients who were refractory to fluoropyrimidines, irinotecan and oxaliplatin with or without targeted agents will be accrued. After checking the eligibility for the study entry, patients will be entered into the study treatment with durvalumab monotherapy. Durvalumab: Study treatment consists of durvalumab 1500 mg Q4W for patients \> 30 kg, and will be repeated every 4 weeks. For patients ≤ 30 kg, weight based dosing of 20 mg/kg durvalumab Q4W will be used. Response evaluation will be performed every 8 weeks (± 1-week window period). Treatment will be continued until disease progression, unacceptable adverse events or the patient's refusal. Treatment through progression is at the investigator's discretion, and the investigator should ensure that patients do not have any significant, unacceptable, or irreversible toxicity that indicate that continuing treatment will not further benefit the patient. The Investigator should ensure that patients still meet all of the inclusion criteria and none of the exclusion criteria for this study.
Gastrointestinal disorders Abdominal pain	6.1% 2/33 • Number of events 3 • Adverse Events were collected through study treatment completion, an average of 1 year and 4months. All-Cause Mortality was assessed up to 46months The term adverse event covers any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation in the clinical study.
Respiratory, thoracic and mediastinal disorders Dyspnea	3.0% 1/33 • Adverse Events were collected through study treatment completion, an average of 1 year and 4months. All-Cause Mortality was assessed up to 46months The term adverse event covers any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation in the clinical study.
Infections and infestations Infection	3.0% 1/33 • Adverse Events were collected through study treatment completion, an average of 1 year and 4months. All-Cause Mortality was assessed up to 46months The term adverse event covers any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation in the clinical study.
Renal and urinary disorders Acute Kidney Injury	6.1% 2/33 • Adverse Events were collected through study treatment completion, an average of 1 year and 4months. All-Cause Mortality was assessed up to 46months The term adverse event covers any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation in the clinical study.
Musculoskeletal and connective tissue disorders Both knee pain	3.0% 1/33 • Adverse Events were collected through study treatment completion, an average of 1 year and 4months. All-Cause Mortality was assessed up to 46months The term adverse event covers any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation in the clinical study.
Metabolism and nutrition disorders Anorexia	3.0% 1/33 • Adverse Events were collected through study treatment completion, an average of 1 year and 4months. All-Cause Mortality was assessed up to 46months The term adverse event covers any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation in the clinical study.
Vascular disorders Thromboembolic event	3.0% 1/33 • Adverse Events were collected through study treatment completion, an average of 1 year and 4months. All-Cause Mortality was assessed up to 46months The term adverse event covers any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation in the clinical study.
Musculoskeletal and connective tissue disorders Back pain	3.0% 1/33 • Adverse Events were collected through study treatment completion, an average of 1 year and 4months. All-Cause Mortality was assessed up to 46months The term adverse event covers any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation in the clinical study.
Reproductive system and breast disorders Atypical ductal hyperplasia of breast	3.0% 1/33 • Adverse Events were collected through study treatment completion, an average of 1 year and 4months. All-Cause Mortality was assessed up to 46months The term adverse event covers any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation in the clinical study.
Skin and subcutaneous tissue disorders Anal fistula	3.0% 1/33 • Adverse Events were collected through study treatment completion, an average of 1 year and 4months. All-Cause Mortality was assessed up to 46months The term adverse event covers any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation in the clinical study.
Metabolism and nutrition disorders Hyperglycemia	3.0% 1/33 • Adverse Events were collected through study treatment completion, an average of 1 year and 4months. All-Cause Mortality was assessed up to 46months The term adverse event covers any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation in the clinical study.

Other adverse events

Other adverse events
Measure	Durvalumab n=33 participants at risk The mismatch repair deficient or microsatellite instable, or POLE mutated metastatic colorectal cancer patients who were refractory to fluoropyrimidines, irinotecan and oxaliplatin with or without targeted agents will be accrued. After checking the eligibility for the study entry, patients will be entered into the study treatment with durvalumab monotherapy. Durvalumab: Study treatment consists of durvalumab 1500 mg Q4W for patients \> 30 kg, and will be repeated every 4 weeks. For patients ≤ 30 kg, weight based dosing of 20 mg/kg durvalumab Q4W will be used. Response evaluation will be performed every 8 weeks (± 1-week window period). Treatment will be continued until disease progression, unacceptable adverse events or the patient's refusal. Treatment through progression is at the investigator's discretion, and the investigator should ensure that patients do not have any significant, unacceptable, or irreversible toxicity that indicate that continuing treatment will not further benefit the patient. The Investigator should ensure that patients still meet all of the inclusion criteria and none of the exclusion criteria for this study.
Endocrine disorders Hyperthyroidism	3.0% 1/33 • Adverse Events were collected through study treatment completion, an average of 1 year and 4months. All-Cause Mortality was assessed up to 46months The term adverse event covers any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation in the clinical study.
Respiratory, thoracic and mediastinal disorders Pneumonitis	3.0% 1/33 • Adverse Events were collected through study treatment completion, an average of 1 year and 4months. All-Cause Mortality was assessed up to 46months The term adverse event covers any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation in the clinical study.
Endocrine disorders Adrenal insufficiency	3.0% 1/33 • Adverse Events were collected through study treatment completion, an average of 1 year and 4months. All-Cause Mortality was assessed up to 46months The term adverse event covers any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation in the clinical study.
Immune system disorders Serum sickness-like reaction	3.0% 1/33 • Adverse Events were collected through study treatment completion, an average of 1 year and 4months. All-Cause Mortality was assessed up to 46months The term adverse event covers any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation in the clinical study.
Investigations Neutrophil count decreased	3.0% 1/33 • Adverse Events were collected through study treatment completion, an average of 1 year and 4months. All-Cause Mortality was assessed up to 46months The term adverse event covers any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation in the clinical study.
Investigations Anemia	12.1% 4/33 • Adverse Events were collected through study treatment completion, an average of 1 year and 4months. All-Cause Mortality was assessed up to 46months The term adverse event covers any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation in the clinical study.
Investigations Platelet count decreased	3.0% 1/33 • Adverse Events were collected through study treatment completion, an average of 1 year and 4months. All-Cause Mortality was assessed up to 46months The term adverse event covers any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation in the clinical study.
Skin and subcutaneous tissue disorders Pruritus	24.2% 8/33 • Adverse Events were collected through study treatment completion, an average of 1 year and 4months. All-Cause Mortality was assessed up to 46months The term adverse event covers any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation in the clinical study.
General disorders Fatigue	15.2% 5/33 • Adverse Events were collected through study treatment completion, an average of 1 year and 4months. All-Cause Mortality was assessed up to 46months The term adverse event covers any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation in the clinical study.
Gastrointestinal disorders Abdominal pain	15.2% 5/33 • Adverse Events were collected through study treatment completion, an average of 1 year and 4months. All-Cause Mortality was assessed up to 46months The term adverse event covers any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation in the clinical study.
Skin and subcutaneous tissue disorders Oral mucositis	15.2% 5/33 • Adverse Events were collected through study treatment completion, an average of 1 year and 4months. All-Cause Mortality was assessed up to 46months The term adverse event covers any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation in the clinical study.
Investigations Increased lipase	12.1% 4/33 • Adverse Events were collected through study treatment completion, an average of 1 year and 4months. All-Cause Mortality was assessed up to 46months The term adverse event covers any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation in the clinical study.
Musculoskeletal and connective tissue disorders Arthralgia	12.1% 4/33 • Adverse Events were collected through study treatment completion, an average of 1 year and 4months. All-Cause Mortality was assessed up to 46months The term adverse event covers any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation in the clinical study.
Gastrointestinal disorders Diarrhea	9.1% 3/33 • Adverse Events were collected through study treatment completion, an average of 1 year and 4months. All-Cause Mortality was assessed up to 46months The term adverse event covers any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation in the clinical study.
Musculoskeletal and connective tissue disorders Myalgia	9.1% 3/33 • Adverse Events were collected through study treatment completion, an average of 1 year and 4months. All-Cause Mortality was assessed up to 46months The term adverse event covers any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation in the clinical study.
Investigations Aspartate aminotransferase increased	9.1% 3/33 • Adverse Events were collected through study treatment completion, an average of 1 year and 4months. All-Cause Mortality was assessed up to 46months The term adverse event covers any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation in the clinical study.
Investigations Alanine aminotransferase increased	9.1% 3/33 • Adverse Events were collected through study treatment completion, an average of 1 year and 4months. All-Cause Mortality was assessed up to 46months The term adverse event covers any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation in the clinical study.
Metabolism and nutrition disorders Anorexia	6.1% 2/33 • Adverse Events were collected through study treatment completion, an average of 1 year and 4months. All-Cause Mortality was assessed up to 46months The term adverse event covers any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation in the clinical study.
Investigations Increased amylase	6.1% 2/33 • Adverse Events were collected through study treatment completion, an average of 1 year and 4months. All-Cause Mortality was assessed up to 46months The term adverse event covers any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation in the clinical study.
Gastrointestinal disorders Nausea	6.1% 2/33 • Adverse Events were collected through study treatment completion, an average of 1 year and 4months. All-Cause Mortality was assessed up to 46months The term adverse event covers any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation in the clinical study.
Gastrointestinal disorders Dyspepsia	6.1% 2/33 • Adverse Events were collected through study treatment completion, an average of 1 year and 4months. All-Cause Mortality was assessed up to 46months The term adverse event covers any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation in the clinical study.
Nervous system disorders Dizziness	6.1% 2/33 • Adverse Events were collected through study treatment completion, an average of 1 year and 4months. All-Cause Mortality was assessed up to 46months The term adverse event covers any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation in the clinical study.
Skin and subcutaneous tissue disorders Eczema	6.1% 2/33 • Adverse Events were collected through study treatment completion, an average of 1 year and 4months. All-Cause Mortality was assessed up to 46months The term adverse event covers any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation in the clinical study.
Endocrine disorders Hypothyroidism	15.2% 5/33 • Adverse Events were collected through study treatment completion, an average of 1 year and 4months. All-Cause Mortality was assessed up to 46months The term adverse event covers any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation in the clinical study.
Vascular disorders Thromboembolism	3.0% 1/33 • Adverse Events were collected through study treatment completion, an average of 1 year and 4months. All-Cause Mortality was assessed up to 46months The term adverse event covers any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation in the clinical study.
Investigations White blood cell decreased	3.0% 1/33 • Adverse Events were collected through study treatment completion, an average of 1 year and 4months. All-Cause Mortality was assessed up to 46months The term adverse event covers any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation in the clinical study.
Gastrointestinal disorders Pancreatitis	6.1% 2/33 • Adverse Events were collected through study treatment completion, an average of 1 year and 4months. All-Cause Mortality was assessed up to 46months The term adverse event covers any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation in the clinical study.
Skin and subcutaneous tissue disorders Skin rash	9.1% 3/33 • Adverse Events were collected through study treatment completion, an average of 1 year and 4months. All-Cause Mortality was assessed up to 46months The term adverse event covers any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation in the clinical study.
Renal and urinary disorders Acute kidney injury	9.1% 3/33 • Adverse Events were collected through study treatment completion, an average of 1 year and 4months. All-Cause Mortality was assessed up to 46months The term adverse event covers any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation in the clinical study.
General disorders Peripheral edema	9.1% 3/33 • Adverse Events were collected through study treatment completion, an average of 1 year and 4months. All-Cause Mortality was assessed up to 46months The term adverse event covers any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation in the clinical study.
Nervous system disorders Peripheral neuropathy	9.1% 3/33 • Adverse Events were collected through study treatment completion, an average of 1 year and 4months. All-Cause Mortality was assessed up to 46months The term adverse event covers any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation in the clinical study.
Metabolism and nutrition disorders Hypercholesterolemia	6.1% 2/33 • Adverse Events were collected through study treatment completion, an average of 1 year and 4months. All-Cause Mortality was assessed up to 46months The term adverse event covers any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation in the clinical study.

Additional Information

Project manager

Academic Research Office, Clinical Trial Center, Asan Medical Center

Phone: 82-2-3010-7187

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place