Trial Outcomes & Findings for Preoperative Immunotherapy (Pembrolizumab) for Patients With Colorectal Cancer and Resectable Hepatic Metastases (NCT NCT03844750)

Last Updated: 2025-12-31

Results Overview

Tumor-infiltrating immune cells (TIICs) will be analyzed by immunohistochemistry (IHC) in pre- and post-pembrolizumab treatment tumor specimens. The proportion of patients with a \>= 2-fold increase (from pre- to post-treatment) in the number of TIICs per unit area (5 high power fields) will be calculated.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

6 participants

Primary outcome timeframe

Up to 2 years

Results posted on

2025-12-31

Participant Flow

Participant milestones

Participant milestones
Measure	Treatment (Vactosertib, Pembrolizumab, Surgery) Neoadjuvant pembrolizumab will be administered at a fixed dose of 200 mg (IV) for 1 cycle plus 200 mg vactosertib (PO once a day (QD), 5 days per week x 2 weeks). Adjuvant pembrolizumab (400 mg IV) + vactosertib (200 mg PO QD Cycle 1, 5 days per week, Cycles 2 and beyond (200 mg twice a day (BID), 5 days per week) will be administered for up to eight 6-week cycles
Overall Study STARTED	6
Overall Study COMPLETED	6
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Preoperative Immunotherapy (Pembrolizumab) for Patients With Colorectal Cancer and Resectable Hepatic Metastases

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Vactosertib, Pembrolizumab, Surgery) n=6 Participants Neoadjuvant pembrolizumab will be administered at a fixed dose of 200 mg (IV) for 1 cycle plus 200 mg vactosertib (PO QD, 5 days per week x 2 weeks). Adjuvant pembrolizumab (400 mg IV) + vactosertib (200 mg PO QD Cycle 1, 5 days per week, Cycles 2 and beyond (200 mg BID, 5 days per week) will be administered for up to eight 6-week cycles
Age, Customized 40 - 49 years old	1 Participants n=1000 Participants
Age, Customized 50 - 59 years old	4 Participants n=1000 Participants
Age, Customized 60 - 69 years old	1 Participants n=1000 Participants
Sex: Female, Male Female	0 Participants n=1000 Participants
Sex: Female, Male Male	6 Participants n=1000 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=1000 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=1000 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=1000 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=1000 Participants
Race (NIH/OMB) Asian	0 Participants n=1000 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=1000 Participants
Race (NIH/OMB) Black or African American	0 Participants n=1000 Participants
Race (NIH/OMB) White	5 Participants n=1000 Participants
Race (NIH/OMB) More than one race	0 Participants n=1000 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=1000 Participants
Region of Enrollment United States	6 participants n=1000 Participants

PRIMARY outcome

Timeframe: Up to 2 years

Population: Due to early study termination by the collaborating sponsor, the funds provided by the collaborating sponsor were no longer available to complete the specific analyses detailed in the primary endpoint. No plans currently exist to fund analysis of this endpoint in the future.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 2 years

Adverse events (AEs) will be analyzed including but not limited to all AEs, serious (S)AEs, and fatal AEs using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5 for classification. Due to the potential for late toxicities from pembrolizumab, patients will be followed for 1 year after their last dose of pembrolizumab.

Outcome measures

Outcome measures
Measure	Treatment (vactosertib, pembrolizumab, surgery) n=6 Participants Neoadjuvant pembrolizumab will be administered at a fixed dose of 200 mg (IV) for 1 cycle plus 200 mg vactosertib (PO QD, 5 days per week x 2 weeks). Adjuvant pembrolizumab (400 mg IV) + vactosertib (200 mg PO QD Cycle 1, 5 days per week, Cycles 2 and beyond (200 mg BID, 5 days per week) will be administered for up to eight 6-week cycles
Proportion of Participants With Treatment-related, Adverse Events	1.00 proportion of participants

SECONDARY outcome

Timeframe: Up to 2 years

Specific immune-related AEs (irAEs) will be collected and designated as immune-related events of clinical interest (ECIs). The study will use descriptive statistics to report on the safety/toxicity. Due to the potential for late toxicities from pembrolizumab, patients will be followed for 1 year after their last dose of pembrolizumab

Outcome measures

Outcome measures
Measure	Treatment (vactosertib, pembrolizumab, surgery) n=6 Participants Neoadjuvant pembrolizumab will be administered at a fixed dose of 200 mg (IV) for 1 cycle plus 200 mg vactosertib (PO QD, 5 days per week x 2 weeks). Adjuvant pembrolizumab (400 mg IV) + vactosertib (200 mg PO QD Cycle 1, 5 days per week, Cycles 2 and beyond (200 mg BID, 5 days per week) will be administered for up to eight 6-week cycles
Proportion of Participants With Events of Clinical Interest (ECIs)	0.33 proportion of participants

SECONDARY outcome

Timeframe: Up to 1 month

The proportion of participants with reported perioperative complications related to study treatment will be reported.

Outcome measures

Outcome measures
Measure	Treatment (vactosertib, pembrolizumab, surgery) n=6 Participants Neoadjuvant pembrolizumab will be administered at a fixed dose of 200 mg (IV) for 1 cycle plus 200 mg vactosertib (PO QD, 5 days per week x 2 weeks). Adjuvant pembrolizumab (400 mg IV) + vactosertib (200 mg PO QD Cycle 1, 5 days per week, Cycles 2 and beyond (200 mg BID, 5 days per week) will be administered for up to eight 6-week cycles
Proportion of Participants With Perioperative Complications	0.17 proportion of participants

SECONDARY outcome

Timeframe: Up to 1 month

Participants who undergo surgical resection of liver metastases will be evaluable and the proportion of participants requiring an R0 resection will be reported

Outcome measures

Outcome measures
Measure	Treatment (vactosertib, pembrolizumab, surgery) n=6 Participants Neoadjuvant pembrolizumab will be administered at a fixed dose of 200 mg (IV) for 1 cycle plus 200 mg vactosertib (PO QD, 5 days per week x 2 weeks). Adjuvant pembrolizumab (400 mg IV) + vactosertib (200 mg PO QD Cycle 1, 5 days per week, Cycles 2 and beyond (200 mg BID, 5 days per week) will be administered for up to eight 6-week cycles
Proportion of Participants With an R0 Resection	0.83 proportion of participants

SECONDARY outcome

Timeframe: Up to 1 year

Population: Only 1 participant underwent partial colectomy at the time of liver resection surgery enabling reliable determination pathological response in the colon primary

Participants who undergo surgical resection of liver metastases will be evaluable and the proportion of participants with a pathological tumor response will be reported

Outcome measures

Outcome measures
Measure	Treatment (vactosertib, pembrolizumab, surgery) n=1 Participants Neoadjuvant pembrolizumab will be administered at a fixed dose of 200 mg (IV) for 1 cycle plus 200 mg vactosertib (PO QD, 5 days per week x 2 weeks). Adjuvant pembrolizumab (400 mg IV) + vactosertib (200 mg PO QD Cycle 1, 5 days per week, Cycles 2 and beyond (200 mg BID, 5 days per week) will be administered for up to eight 6-week cycles
Proportion of Participants With a Pathologic Response	0 proportion of participants

SECONDARY outcome

Timeframe: Up to the time of surgery, approximately 14 days

Population: Due to funding constraints, the non-standard of care (planned as research-funded) radiological scan originally planned for this short-interval ORR endpoint was not performed. Therefore, no data for ORR between baseline and date of surgery was collected.

ORR is defined as the radiographic response as measured from baseline until the day of surgery will be evaluated using RECIST. Participants with a radiographic complete response (CR) or partial response (PR) before surgery will be reported.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 2 years from day of surgery

The time from objective response defined as radiographic evidence of relapse on surveillance CT scans after surgery to progression or death, whichever occurs first, will be used to determine relapse-free survival for participants who received adjuvant vactosertib and pembrolizumab.

Outcome measures

Outcome measures
Measure	Treatment (vactosertib, pembrolizumab, surgery) n=4 Participants Neoadjuvant pembrolizumab will be administered at a fixed dose of 200 mg (IV) for 1 cycle plus 200 mg vactosertib (PO QD, 5 days per week x 2 weeks). Adjuvant pembrolizumab (400 mg IV) + vactosertib (200 mg PO QD Cycle 1, 5 days per week, Cycles 2 and beyond (200 mg BID, 5 days per week) will be administered for up to eight 6-week cycles
Median Relapse-free Survival (RFS)	14.51 months Interval 4.44 to There were insufficient number of events so an upper limit to the confidence interval could not be calculated.

Adverse Events

Treatment (Vactosertib, Pembrolizumab, Surgery)

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (Vactosertib, Pembrolizumab, Surgery) n=6 participants at risk Neoadjuvant pembrolizumab will be administered at a fixed dose of 200 mg (IV) for 1 cycle plus 200 mg vactosertib (PO QD, 5 days per week x 2 weeks). Adjuvant pembrolizumab (400 mg IV) + vactosertib (200 mg PO QD Cycle 1, 5 days per week, Cycles 2 and beyond (200 mg BID, 5 days per week) will be administered for up to eight 6-week cycles
Gastrointestinal disorders Colitis	16.7% 1/6 • Number of events 1 • Up to 2 years

Other adverse events

Other adverse events
Measure	Treatment (Vactosertib, Pembrolizumab, Surgery) n=6 participants at risk Neoadjuvant pembrolizumab will be administered at a fixed dose of 200 mg (IV) for 1 cycle plus 200 mg vactosertib (PO QD, 5 days per week x 2 weeks). Adjuvant pembrolizumab (400 mg IV) + vactosertib (200 mg PO QD Cycle 1, 5 days per week, Cycles 2 and beyond (200 mg BID, 5 days per week) will be administered for up to eight 6-week cycles
Blood and lymphatic system disorders Anemia	16.7% 1/6 • Number of events 3 • Up to 2 years
Endocrine disorders Hyperthyroidism	16.7% 1/6 • Number of events 1 • Up to 2 years
Endocrine disorders Hypothyroidism	33.3% 2/6 • Number of events 3 • Up to 2 years
Gastrointestinal disorders Abdominal distension	33.3% 2/6 • Number of events 2 • Up to 2 years
Gastrointestinal disorders Abdominal pain	16.7% 1/6 • Number of events 1 • Up to 2 years
Gastrointestinal disorders Colitis	16.7% 1/6 • Number of events 2 • Up to 2 years
Gastrointestinal disorders Nausea	33.3% 2/6 • Number of events 3 • Up to 2 years
Gastrointestinal disorders Diarrhea	16.7% 1/6 • Number of events 1 • Up to 2 years
General disorders Edema limbs	16.7% 1/6 • Number of events 1 • Up to 2 years
General disorders Fatigue	50.0% 3/6 • Number of events 3 • Up to 2 years
General disorders Pain	16.7% 1/6 • Number of events 1 • Up to 2 years
Investigations Neutrophil count decreased	16.7% 1/6 • Number of events 1 • Up to 2 years
Investigations Platelet count decreased	16.7% 1/6 • Number of events 1 • Up to 2 years
Metabolism and nutrition disorders Anorexia	16.7% 1/6 • Number of events 1 • Up to 2 years
Metabolism and nutrition disorders Hypercalcemia	33.3% 2/6 • Number of events 2 • Up to 2 years
Musculoskeletal and connective tissue disorders Pain in extremity	33.3% 2/6 • Number of events 2 • Up to 2 years
Musculoskeletal and connective tissue disorders Back Pain	16.7% 1/6 • Number of events 1 • Up to 2 years
Nervous system disorders Headache	50.0% 3/6 • Number of events 5 • Up to 2 years
Nervous system disorders Peripheral sensory neuropathy	33.3% 2/6 • Number of events 2 • Up to 2 years
Renal and urinary disorders Acute kidney injury	33.3% 2/6 • Number of events 2 • Up to 2 years
Respiratory, thoracic and mediastinal disorders Cough	33.3% 2/6 • Number of events 2 • Up to 2 years
Skin and subcutaneous tissue disorders Pruritus	16.7% 1/6 • Number of events 1 • Up to 2 years
Skin and subcutaneous tissue disorders Rash acneiform	16.7% 1/6 • Number of events 1 • Up to 2 years
Skin and subcutaneous tissue disorders Hyperhidrosis	33.3% 2/6 • Number of events 3 • Up to 2 years
Skin and subcutaneous tissue disorders Rash maculo-papular	50.0% 3/6 • Number of events 6 • Up to 2 years
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders, Other	16.7% 1/6 • Number of events 1 • Up to 2 years
Vascular disorders Thromboembolic event	16.7% 1/6 • Number of events 1 • Up to 2 years

Additional Information

Dr. Chloe Atreya, MD

University of California, San Francisco

Phone: (415) 476-1000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place