Trial Outcomes & Findings for Study of Durvalumab and Tremelimumab After Radiation for Microsatellite Stable Metastatic Colorectal Cancer Progressing on Chemotherapy (NCT NCT03007407)

Last Updated: 2022-12-05

Results Overview

Complete Response (CR): Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be \<10mm on the short axis. Partial Response (PR): 30% or more decrease in the sum of diameters of target lesions. The reference the baseline sums of diameters. Progressive Disease (PD): 20% or more increase in the sum of diameters of target lesions. The reference is the smallest sum while on study (including the baseline sum if that is the smallest on study). In addition to the relative 20% increase, the sum must also demonstrate an absolute increase 5mm or more. (Note: any appearance of one or more new lesions is also considered progression).Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. The reference is the smallest sum of diameters while on study.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

33 participants

Primary outcome timeframe

Through treatment, up to 1.3 years

Results posted on

2022-12-05

Participant Flow

Participant milestones

Participant milestones
Measure	Durvalumab and Tremelimumab durvalumab: Following three doses of hypofractionated palliative radiation (Days -2, -1, and Day 0 prior to Cycle 1), patients will receive durvalumab (1500 mg IV infusion) on Day 1 for 4 cycles (in combination with tremelimumab). Beginning with Cycle 5 through Cycle 12, patients will receive durvalumab alone (1500 mg/IV infusion) on Day 1 of each 28 day cycle. Tremelimumab: Following three doses of hypofractionated palliative radiation (Days -2, -1, and Day 0 prior to Cycle 1), patients will receive tremelimumab (75 mg IV infusion) on Day 1 for 4 cycles (in combination with durvalumab).
Overall Study STARTED	33
Overall Study COMPLETED	21
Overall Study NOT COMPLETED	12

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study of Durvalumab and Tremelimumab After Radiation for Microsatellite Stable Metastatic Colorectal Cancer Progressing on Chemotherapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Durvalumab and Tremelimumab n=21 Participants durvalumab: Following three doses of hypofractionated palliative radiation (Days -2, -1, and Day 0 prior to Cycle 1), patients will receive durvalumab (1500 mg IV infusion) on Day 1 for 4 cycles (in combination with tremelimumab). Beginning with Cycle 5 through Cycle 12, patients will receive durvalumab alone (1500 mg/IV infusion) on Day 1 of each 28 day cycle. Tremelimumab: Following three doses of hypofractionated palliative radiation (Days -2, -1, and Day 0 prior to Cycle 1), patients will receive tremelimumab (75 mg IV infusion) on Day 1 for 4 cycles (in combination with durvalumab).
Age, Continuous	58 years n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants
Race/Ethnicity, Customized Asian	2 Participants n=5 Participants
Race/Ethnicity, Customized Black	1 Participants n=5 Participants
Race/Ethnicity, Customized White	18 Participants n=5 Participants
Race/Ethnicity, Customized Non Hispanic	21 Participants n=5 Participants

PRIMARY outcome

Timeframe: Through treatment, up to 1.3 years

Outcome measures

Outcome measures
Measure	Durvalumab and Tremelimumab n=21 Participants durvalumab: Following three doses of hypofractionated palliative radiation (Days -2, -1, and Day 0 prior to Cycle 1), patients will receive durvalumab (1500 mg IV infusion) on Day 1 for 4 cycles (in combination with tremelimumab). Beginning with Cycle 5 through Cycle 12, patients will receive durvalumab alone (1500 mg/IV infusion) on Day 1 of each 28 day cycle. Tremelimumab: Following three doses of hypofractionated palliative radiation (Days -2, -1, and Day 0 prior to Cycle 1), patients will receive tremelimumab (75 mg IV infusion) on Day 1 for 4 cycles (in combination with durvalumab).
Overall Objective Response Rate (ORR) of Dual Immune Checkpoint Blockade by RECIST 1.1	9.52 percentage of participants Interval 1.17 to 30.38

SECONDARY outcome

Timeframe: At 16 weeks

Percentage of patients who have achieved clinical benefit defined as CR (complete response) and PR (partial response) and stable disease that lasts at least 4 months

Outcome measures

Outcome measures
Measure	Durvalumab and Tremelimumab n=21 Participants durvalumab: Following three doses of hypofractionated palliative radiation (Days -2, -1, and Day 0 prior to Cycle 1), patients will receive durvalumab (1500 mg IV infusion) on Day 1 for 4 cycles (in combination with tremelimumab). Beginning with Cycle 5 through Cycle 12, patients will receive durvalumab alone (1500 mg/IV infusion) on Day 1 of each 28 day cycle. Tremelimumab: Following three doses of hypofractionated palliative radiation (Days -2, -1, and Day 0 prior to Cycle 1), patients will receive tremelimumab (75 mg IV infusion) on Day 1 for 4 cycles (in combination with durvalumab).
Percentage of Patients Who Have Achieved Clinical Benefit	14.29 percentage of participants Interval 3.05 to 36.34

SECONDARY outcome

Timeframe: Through study completetion (1.3 years)

Median time from study entry until documentation of progression (years) in half of the patients as determined by RECIST 1.1.

Outcome measures

Outcome measures
Measure	Durvalumab and Tremelimumab n=21 Participants durvalumab: Following three doses of hypofractionated palliative radiation (Days -2, -1, and Day 0 prior to Cycle 1), patients will receive durvalumab (1500 mg IV infusion) on Day 1 for 4 cycles (in combination with tremelimumab). Beginning with Cycle 5 through Cycle 12, patients will receive durvalumab alone (1500 mg/IV infusion) on Day 1 of each 28 day cycle. Tremelimumab: Following three doses of hypofractionated palliative radiation (Days -2, -1, and Day 0 prior to Cycle 1), patients will receive tremelimumab (75 mg IV infusion) on Day 1 for 4 cycles (in combination with durvalumab).
Median Duration of Response to mCRC (Metastic Colorectal Cancer) Responds to Study Therapy	0.85 years Interval 0.0 to The upper limit of the 95% CI is infinite.

SECONDARY outcome

Timeframe: During treatment (max of 12 cycles; each cycle 28 days) to 90 days after last dose of study therapy

Population: Number of participants analyzed represents the number of patients with toxicity information (29).

Frequency of adverse events categorized using the NCI Common Terminology Criteria for Adverse Events version 4.0

Outcome measures

Outcome measures
Measure	Durvalumab and Tremelimumab n=29 Participants durvalumab: Following three doses of hypofractionated palliative radiation (Days -2, -1, and Day 0 prior to Cycle 1), patients will receive durvalumab (1500 mg IV infusion) on Day 1 for 4 cycles (in combination with tremelimumab). Beginning with Cycle 5 through Cycle 12, patients will receive durvalumab alone (1500 mg/IV infusion) on Day 1 of each 28 day cycle. Tremelimumab: Following three doses of hypofractionated palliative radiation (Days -2, -1, and Day 0 prior to Cycle 1), patients will receive tremelimumab (75 mg IV infusion) on Day 1 for 4 cycles (in combination with durvalumab).
Frequency of Adverse Events Assessed by CTCAE 4.0, From Beginning of Treatment to 90 Days After Last Dose Total	29 Participants
Frequency of Adverse Events Assessed by CTCAE 4.0, From Beginning of Treatment to 90 Days After Last Dose Grade 0	2 Participants
Frequency of Adverse Events Assessed by CTCAE 4.0, From Beginning of Treatment to 90 Days After Last Dose Grade 1	3 Participants
Frequency of Adverse Events Assessed by CTCAE 4.0, From Beginning of Treatment to 90 Days After Last Dose Grade 2	6 Participants
Frequency of Adverse Events Assessed by CTCAE 4.0, From Beginning of Treatment to 90 Days After Last Dose Grade 3	14 Participants
Frequency of Adverse Events Assessed by CTCAE 4.0, From Beginning of Treatment to 90 Days After Last Dose Grade 4	3 Participants
Frequency of Adverse Events Assessed by CTCAE 4.0, From Beginning of Treatment to 90 Days After Last Dose Grade 5	1 Participants

Adverse Events

Durvalumab and Tremelimumab

Serious events: 0 serious events

Other events: 29 other events

Deaths: 6 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Durvalumab and Tremelimumab n=29 participants at risk durvalumab: Following three doses of hypofractionated palliative radiation (Days -2, -1, and Day 0 prior to Cycle 1), patients will receive durvalumab (1500 mg IV infusion) on Day 1 for 4 cycles (in combination with tremelimumab). Beginning with Cycle 5 through Cycle 12, patients will receive durvalumab alone (1500 mg/IV infusion) on Day 1 of each 28 day cycle. Tremelimumab: Following three doses of hypofractionated palliative radiation (Days -2, -1, and Day 0 prior to Cycle 1), patients will receive tremelimumab (75 mg IV infusion) on Day 1 for 4 cycles (in combination with durvalumab).
Blood and lymphatic system disorders Anemia	10.3% 3/29 • From the first dose of study therapy until 90 days after the last dose of study therapy.
Endocrine disorders Hypothyroidism	6.9% 2/29 • From the first dose of study therapy until 90 days after the last dose of study therapy.
Gastrointestinal disorders Abdominal pain	10.3% 3/29 • From the first dose of study therapy until 90 days after the last dose of study therapy.
Gastrointestinal disorders Constipation	13.8% 4/29 • From the first dose of study therapy until 90 days after the last dose of study therapy.
Gastrointestinal disorders Diarrhea	20.7% 6/29 • From the first dose of study therapy until 90 days after the last dose of study therapy.
Gastrointestinal disorders Nausea	17.2% 5/29 • From the first dose of study therapy until 90 days after the last dose of study therapy.
General disorders Fatigue	37.9% 11/29 • From the first dose of study therapy until 90 days after the last dose of study therapy.
General disorders Fever	17.2% 5/29 • From the first dose of study therapy until 90 days after the last dose of study therapy.
General disorders Non-cardiac chest pain	6.9% 2/29 • From the first dose of study therapy until 90 days after the last dose of study therapy.
Investigations Weight loss	6.9% 2/29 • From the first dose of study therapy until 90 days after the last dose of study therapy.
Metabolism and nutrition disorders Anorexia	17.2% 5/29 • From the first dose of study therapy until 90 days after the last dose of study therapy.
Metabolism and nutrition disorders Dehydration	6.9% 2/29 • From the first dose of study therapy until 90 days after the last dose of study therapy.
Respiratory, thoracic and mediastinal disorders Cough	6.9% 2/29 • From the first dose of study therapy until 90 days after the last dose of study therapy.
Skin and subcutaneous tissue disorders Dry Skin	6.9% 2/29 • From the first dose of study therapy until 90 days after the last dose of study therapy.
Skin and subcutaneous tissue disorders Itching	10.3% 3/29 • From the first dose of study therapy until 90 days after the last dose of study therapy.
Skin and subcutaneous tissue disorders Maculopapular rash	17.2% 5/29 • From the first dose of study therapy until 90 days after the last dose of study therapy.
Skin and subcutaneous tissue disorders Pruritus	17.2% 5/29 • From the first dose of study therapy until 90 days after the last dose of study therapy.
Skin and subcutaneous tissue disorders Rash maculo-papular	13.8% 4/29 • From the first dose of study therapy until 90 days after the last dose of study therapy.

Additional Information

Director, Department of Site and Study Management

NSABP Foundation

Phone: 1-800-270-3165

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60