Trial Outcomes & Findings for Tremelimumab and Durvalumab in Treating Patients With Colorectal Cancer With Liver Metastases That Can Be Removed by Surgery (NCT NCT02754856)

Last Updated: 2024-10-09

Results Overview

Post-operative toxicity graded by the Clavien-Dindo classification. The Clavien Dindo Classification is used to rank the severity of a surgical complication. It is based on the type of therapy needed to correct the complication. The scale consists of several grades (Grade I, II, IIIa, IIIb, IVa, IVb and V). Grade I complications are usually mild but Grade II and higher complications are more significant.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

24 participants

Primary outcome timeframe

3 years

Results posted on

2024-10-09

Participant Flow

8/2016 -1/2019

24 participants started and 1 participate withdrew from study( 23 participants completed the study)

Participant milestones

Participant milestones
Measure	Durvalumab/Tremelimumab Neoadjuvant tremelimumab 75 mg IV flat dose and durvalumab 1500 mg IV flat dose given pre-operatively for 1 cycle prior to CRC liver metastases resection. Post-operative therapy was at the discretion of the treating physician, and patients were eligible to receive durvalumab 1500 mg IV every 4 weeks for 4 cycles.
Overall Study STARTED	24
Overall Study COMPLETED	23
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Durvalumab/Tremelimumab Neoadjuvant tremelimumab 75 mg IV flat dose and durvalumab 1500 mg IV flat dose given pre-operatively for 1 cycle prior to CRC liver metastases resection. Post-operative therapy was at the discretion of the treating physician, and patients were eligible to receive durvalumab 1500 mg IV every 4 weeks for 4 cycles.
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Tremelimumab and Durvalumab in Treating Patients With Colorectal Cancer With Liver Metastases That Can Be Removed by Surgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Durvalumab/Tremelimumab n=23 Participants Neoadjuvant tremelimumab 75 mg IV flat dose and durvalumab 1500 mg IV flat dose given pre-operatively for 1 cycle prior to CRC liver metastases resection. Post-operative therapy was at the discretion of the treating physician, and patients were eligible to receive durvalumab 1500 mg IV every 4 weeks for 4 cycles.
Age, Continuous	56 Years n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	23 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	23 Participants n=5 Participants
Region of Enrollment United States	23 Participants n=5 Participants

PRIMARY outcome

Timeframe: 3 years

Population: 3 patients did not undergo surgical exploration because of progression of previously noted sub-centimeter lung nodules.

Outcome measures

Outcome measures
Measure	Durvalumab/Tremelimumab n=20 Participants Neoadjuvant tremelimumab 75 mg IV flat dose and durvalumab 1500 mg IV flat dose given pre-operatively for 1 cycle prior to CRC liver metastases resection. Post-operative therapy was at the discretion of the treating physician, and patients were eligible to receive durvalumab 1500 mg IV every 4 weeks for 4 cycles.
Post-operative Toxicity	8 Participants

PRIMARY outcome

Timeframe: 3 years

Feasibility and safety assessed by the rate of on-trial surgical resection of liver metastases, post-operative toxicity graded by the Clavien-Dindo classification, and treatment related toxicity graded by CTCAE v5. The combination was defined as feasible if at least 80% of participants could undergo resection or if between 60% and 80% could undergo resection with a positive toxicity and efficacy profile.

Outcome measures

Outcome measures
Measure	Durvalumab/Tremelimumab n=20 Participants Neoadjuvant tremelimumab 75 mg IV flat dose and durvalumab 1500 mg IV flat dose given pre-operatively for 1 cycle prior to CRC liver metastases resection. Post-operative therapy was at the discretion of the treating physician, and patients were eligible to receive durvalumab 1500 mg IV every 4 weeks for 4 cycles.
Feasibility and Safety in the Conduct of the Trial Surgical resection	17 Participants
Feasibility and Safety in the Conduct of the Trial Exploration, no resection	3 Participants

SECONDARY outcome

Timeframe: 3 years

Population: Grade 3/4 treatment-related immune toxicity and postoperative grade 3/4 toxicity

Treatment related toxicity graded by CTCAE v5

Outcome measures

Outcome measures
Measure	Durvalumab/Tremelimumab n=23 Participants Neoadjuvant tremelimumab 75 mg IV flat dose and durvalumab 1500 mg IV flat dose given pre-operatively for 1 cycle prior to CRC liver metastases resection. Post-operative therapy was at the discretion of the treating physician, and patients were eligible to receive durvalumab 1500 mg IV every 4 weeks for 4 cycles.
Treatment Related Toxicity	22 percentage of participants Interval 10.0 to 44.0

SECONDARY outcome

Timeframe: 2 years

Pre-operative response rate evaluation using RECIST v1.1. RECIST 1.1 will be used to identify measurable disease on baseline CT scans. Tumor measurements will be made upon restaging CT scans prior to surgery. No tumor measurements will take place post-operatively as the goal of therapy is no evidence of disease. Pre-surgery response will be classified into Complete Response, Partial Response, Stable Disease and Progressive Disease.

Outcome measures

Outcome measures
Measure	Durvalumab/Tremelimumab n=23 Participants Neoadjuvant tremelimumab 75 mg IV flat dose and durvalumab 1500 mg IV flat dose given pre-operatively for 1 cycle prior to CRC liver metastases resection. Post-operative therapy was at the discretion of the treating physician, and patients were eligible to receive durvalumab 1500 mg IV every 4 weeks for 4 cycles.
Pre-operative Response Rate Progressive disease	5 Participants
Pre-operative Response Rate Stable Disease	15 Participants
Pre-operative Response Rate Patial Response	3 Participants

SECONDARY outcome

Timeframe: 3 years

The time from date of curative surgery to the time of recurrence or death

Outcome measures

Outcome measures
Measure	Durvalumab/Tremelimumab n=23 Participants Neoadjuvant tremelimumab 75 mg IV flat dose and durvalumab 1500 mg IV flat dose given pre-operatively for 1 cycle prior to CRC liver metastases resection. Post-operative therapy was at the discretion of the treating physician, and patients were eligible to receive durvalumab 1500 mg IV every 4 weeks for 4 cycles.
Relapse-Free Survival (RFS)	9.7 Months Interval 1.3 to 28.0

SECONDARY outcome

Timeframe: 3 years

The time from treatment to death, regardless of disease recurrence.

Outcome measures

Outcome measures
Measure	Durvalumab/Tremelimumab n=23 Participants Neoadjuvant tremelimumab 75 mg IV flat dose and durvalumab 1500 mg IV flat dose given pre-operatively for 1 cycle prior to CRC liver metastases resection. Post-operative therapy was at the discretion of the treating physician, and patients were eligible to receive durvalumab 1500 mg IV every 4 weeks for 4 cycles.
Overall Survival	24.5 months Interval 16.5 to 28.4

SECONDARY outcome

Timeframe: 3 years

Tumor immune markers was evaluated using flow cytometry, Multiplex Immunofluorescence (mIF) and Immunohistochemistry (IHC) analyses, RNA sequencing, Microbial DNA isolation and 16S rRNA gene sequencing (using QIAamp DNA stool mini kit on pretreatment feacal samples)

Outcome measures

Outcome measures
Measure	Durvalumab/Tremelimumab n=23 Participants Neoadjuvant tremelimumab 75 mg IV flat dose and durvalumab 1500 mg IV flat dose given pre-operatively for 1 cycle prior to CRC liver metastases resection. Post-operative therapy was at the discretion of the treating physician, and patients were eligible to receive durvalumab 1500 mg IV every 4 weeks for 4 cycles.
Translational Evaluation of Various Immune-relevant Factors POLE mutation B	2 Participants
Translational Evaluation of Various Immune-relevant Factors BRAF mutation	1 Participants
Translational Evaluation of Various Immune-relevant Factors KRAS mutation	12 Participants
Translational Evaluation of Various Immune-relevant Factors TP53 mutation	14 Participants
Translational Evaluation of Various Immune-relevant Factors APC mutation	11 Participants
Translational Evaluation of Various Immune-relevant Factors pMMR	21 Participants
Translational Evaluation of Various Immune-relevant Factors dMMR	2 Participants
Translational Evaluation of Various Immune-relevant Factors CMS1	0 Participants
Translational Evaluation of Various Immune-relevant Factors CMS2	7 Participants
Translational Evaluation of Various Immune-relevant Factors CMS3	4 Participants
Translational Evaluation of Various Immune-relevant Factors CMS4	4 Participants

Adverse Events

Durvalumab/Tremelimumab

Serious events: 0 serious events

Other events: 23 other events

Deaths: 1 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Durvalumab/Tremelimumab n=23 participants at risk Neoadjuvant tremelimumab 75 mg IV flat dose and durvalumab 1500 mg IV flat dose given pre-operatively for 1 cycle prior to CRC liver metastases resection. Post-operative therapy was at the discretion of the treating physician, and patients were eligible to receive durvalumab 1500 mg IV every 4 weeks for 4 cycles.
Investigations Anemia	8.7% 2/23 • Up to 3 years Treatment related toxicity was assessed and graded using CTCAE v5
Investigations Decreased neutrophil count	8.7% 2/23 • Up to 3 years Treatment related toxicity was assessed and graded using CTCAE v5
Investigations Decreased platelet count	13.0% 3/23 • Up to 3 years Treatment related toxicity was assessed and graded using CTCAE v5
Investigations Decreased white blood cells	4.3% 1/23 • Up to 3 years Treatment related toxicity was assessed and graded using CTCAE v5
Investigations Hypokalemia	4.3% 1/23 • Up to 3 years Treatment related toxicity was assessed and graded using CTCAE v5
Investigations Hyponatremia	4.3% 1/23 • Up to 3 years Treatment related toxicity was assessed and graded using CTCAE v5
Investigations Increased alanine aminotransferase	8.7% 2/23 • Up to 3 years Treatment related toxicity was assessed and graded using CTCAE v5
Investigations Increased alkaline phosphatase	8.7% 2/23 • Up to 3 years Treatment related toxicity was assessed and graded using CTCAE v5
Investigations Increased aspartate aminotransferase	13.0% 3/23 • Up to 3 years Treatment related toxicity was assessed and graded using CTCAE v5
Investigations Lipase increased	8.7% 2/23 • Up to 3 years Treatment related toxicity was assessed and graded using CTCAE v5
Endocrine disorders Adrenal insufficiency	4.3% 1/23 • Up to 3 years Treatment related toxicity was assessed and graded using CTCAE v5
Endocrine disorders Hyperthyroidism	4.3% 1/23 • Up to 3 years Treatment related toxicity was assessed and graded using CTCAE v5
Endocrine disorders Hypothyroidism	13.0% 3/23 • Up to 3 years Treatment related toxicity was assessed and graded using CTCAE v5
Investigations Serum amylase increased	4.3% 1/23 • Up to 3 years Treatment related toxicity was assessed and graded using CTCAE v5
Gastrointestinal disorders Anorexia	4.3% 1/23 • Up to 3 years Treatment related toxicity was assessed and graded using CTCAE v5
Gastrointestinal disorders Constipation	8.7% 2/23 • Up to 3 years Treatment related toxicity was assessed and graded using CTCAE v5
Gastrointestinal disorders Diarrhea	13.0% 3/23 • Up to 3 years Treatment related toxicity was assessed and graded using CTCAE v5
Gastrointestinal disorders Nausea	13.0% 3/23 • Up to 3 years Treatment related toxicity was assessed and graded using CTCAE v5
Gastrointestinal disorders Rectal hemorrhage	4.3% 1/23 • Up to 3 years Treatment related toxicity was assessed and graded using CTCAE v5
General disorders Chills	8.7% 2/23 • Up to 3 years Treatment related toxicity was assessed and graded using CTCAE v5
General disorders Fatigue	43.5% 10/23 • Up to 3 years Treatment related toxicity was assessed and graded using CTCAE v5
General disorders Fever	13.0% 3/23 • Up to 3 years Treatment related toxicity was assessed and graded using CTCAE v5
General disorders Hypotention	4.3% 1/23 • Up to 3 years Treatment related toxicity was assessed and graded using CTCAE v5
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Anxiety	4.3% 1/23 • Up to 3 years Treatment related toxicity was assessed and graded using CTCAE v5
Nervous system disorders Peripheral motor neuropathy	4.3% 1/23 • Up to 3 years Treatment related toxicity was assessed and graded using CTCAE v5
Nervous system disorders Peripheral sensory neuropathy	4.3% 1/23 • Up to 3 years Treatment related toxicity was assessed and graded using CTCAE v5
Vascular disorders Thromboembolic event	4.3% 1/23 • Up to 3 years Treatment related toxicity was assessed and graded using CTCAE v5
Skin and subcutaneous tissue disorders Skin hyperpigmentation	4.3% 1/23 • Up to 3 years Treatment related toxicity was assessed and graded using CTCAE v5
Skin and subcutaneous tissue disorders Rash (maculo-papular)	8.7% 2/23 • Up to 3 years Treatment related toxicity was assessed and graded using CTCAE v5
Skin and subcutaneous tissue disorders Rash (acneiform)	8.7% 2/23 • Up to 3 years Treatment related toxicity was assessed and graded using CTCAE v5
Skin and subcutaneous tissue disorders Pruritis	17.4% 4/23 • Up to 3 years Treatment related toxicity was assessed and graded using CTCAE v5
Gastrointestinal disorders Oral mucositis	4.3% 1/23 • Up to 3 years Treatment related toxicity was assessed and graded using CTCAE v5
Musculoskeletal and connective tissue disorders Myalgia	4.3% 1/23 • Up to 3 years Treatment related toxicity was assessed and graded using CTCAE v5
Psychiatric disorders Insomnia	4.3% 1/23 • Up to 3 years Treatment related toxicity was assessed and graded using CTCAE v5
Injury, poisoning and procedural complications Infusion related reaction	8.7% 2/23 • Up to 3 years Treatment related toxicity was assessed and graded using CTCAE v5
Musculoskeletal and connective tissue disorders Arthralgia	4.3% 1/23 • Up to 3 years Treatment related toxicity was assessed and graded using CTCAE v5
Respiratory, thoracic and mediastinal disorders Dyspnea	4.3% 1/23 • Up to 3 years Treatment related toxicity was assessed and graded using CTCAE v5
Respiratory, thoracic and mediastinal disorders Epistaxis	8.7% 2/23 • Up to 3 years Treatment related toxicity was assessed and graded using CTCAE v5

Additional Information

Dr. Michael Overman

University of Texas M D Anderson Cancer Center

Phone: (713) 792-2828

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place