A Phase 2 interventional study of Regorafenib and Pembrolizumab in MSI-H Colorectal Cancer, sponsored by Anwaar Saeed. Terminated at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-01-20.
Sponsored by Anwaar Saeed · Phase 2, Interventional, and Treatment
This is a trial of Regorafenib in combination with pembrolizumab for patients with MSI-H colorectal cancer consisting of lead-in phase examining preliminary efficacy and safety, followed by a randomized phase to further examine efficacy.
Regorafenib is a multi-kinase inhibitor that targets several receptor tyrosine kinases including vascular endothelial growth factor receptor (VEGFR). Regorafenib may also have immunomodulatory affect in the tumor microenvironment. Preclinical and early clinical studies indicate there is a potential for synergistic activity of regorafenib with immune checkpoint inhibitors that can be leveraged to augment antitumor immunity. Pembrolizumab, anti-PD1 blockade, has been approved for patients with high microsatellite instability (MSI-H) colorectal cancer (CRC) as first line therapy. However, there is still an unmet need to enhance the efficacy of immune checkpoint inhibitors for patients with MSI-H colorectal cancer. The efficacy of TKI and immune checkpoint inhibitor combination have been shown in clinical studies for solid tumors particularly for those that are responsive to immune checkpoint inhibitors therapy. Therefore, there is strong rationale for the combination of regorafenib and pembrolizumab in MSI-H colorectal cancer in which there is increased VEGF activity compared to MSS counterpart. A recent retrospective study showed significantly improved response to regorafenib among patients with MSI-H colorectal cancer, compared to patients with MSS colorectal cancer. Collectively, this combination may increase anti-tumor immune response and clinical effectiveness of immunotherapy for patients with MSI-H colorectal cancer. Based on prior clinical trials, the target regorafenib dose in this study is determined to be 90 mg. However, patients in the lead-in phase will receive regorafenib 60 mg in combination with 200mg of pembrolizumab Q3 weeks in the first cycle to increase tolerance and study compliance. The dose of regorafenib will be increased to 90 mg by Cycle 2. An interim analysis will be performed after completion of data collection for the lead-in phase. Target enrollment for the lead-in phase is approximately 22 patients. Following the futility analysis in lead-in phase, the randomized phase target enrollment is determined to be 66 patients per arm, for a total trial enrollment of 154 participants. Patients who received 3 or less cycles of chemotherapy prior to the determination of MMR-D and MSI-H disease can be enrolled in this trial.
Anwaar Saeed is the lead sponsor of 5 studies on the registry; 3 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Adequate organ function based on the following lab assessments:
Exclusion Criteria:
Any hemorrhage or bleeding event ≥ CTCAE Grade 3 within 4 weeks prior to the start of study medication:
Pembrolizumab: 200mg, Q3 weeks Regorafenib: 60mg Cycle 1 Day 1 90 mg Cycle 2 Day 1
Drug: Regorafenib · Drug: Pembrolizumab
Pembrolizumab: 200mg, Q3 weeks
Drug: Pembrolizumab
A multi-kinase inhibitor that targets several receptor tyrosine kinases including vascular endothelial growth factor receptor (VEGFR), which may also have immunomodulatory affect in the tumor microenvironment.
Also known as: BAY 73-4506, Stivarga
An anti-PD1 blockade / immune checkpoint inhibitor treatment approved for patients with high microsatellite instability (MSI-H) colorectal cancer (CRC) as first line therapy.
Also known as: Keytruda
Objective Response Rate (ORR), Lead-in Phase
Percentage of patients with partial response (PR) or complete response (CR) to the treatment per RECIST 1.1. criteria. v1.1. Per RECIST v1.1: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (target or nontarget) with reduction in short axis to \<10 mm. Partial Response (PR): ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: Up to 12 months (lead-in phase)
Progression-free Survival (PFS), Randomize Phase
Median number of months from time of randomization to the date of disease progression or death from any cause. Per RECISIT v1.1: Progressive Disease (PD):≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.
Time frame: Up to 24 months
Adverse Events and Serious Adverse Events Related to Treatment
Percentage of patients that experience Adverse Events (AEs) and/or Serious Adverse Events (SAEs) related to study treatment, per NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0. The maximum grade for each type of toxicity will be recorded for each patient.
Time frame: Up to 24 months (lead-in phase)
Adverse Events and Serious Adverse Events Related to Treatment
Percentage of patients that experience Adverse Events (AEs) and/or Serious Adverse Events (SAEs) related to study treatment, per NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0. The maximum grade for each type of toxicity will be recorded for each patient.
Time frame: Up to 24 months (beginning at start of post lead-in phase)
Progression-free Survival (PFS), Lead-In Phase
Median number of months from time of randomization to the date of disease progression or death from any cause. Per RECISIT v1.1: Progressive Disease (PD):≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.
Time frame: Up to 24 months
Overall Survival (OS)
Median number of months from start of treatment to death from any cause.
Time frame: Up to 48 months (lead-in phase)
Overall Survival (OS)
Median number of months from time of randomization to death from any cause.
Time frame: Up to 24 months (beginning at start of post lead-in phase)
Objective Response Rate (ORR), Randomized Phase
Percentage of patients with partial response (PR) or complete response (CR) to the treatment per RECIST 1.1. criteria. v1.1. Per RECIST v1.1: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (target or nontarget) with reduction in short axis to \<10 mm. Partial Response (PR): ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: Up to 12 months (beginning at start of post lead-in phase)
Plan to share: No
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This study is terminated, as verified in Jan 2026. You cannot join it, but the record below documents what was studied.
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Anwaar Saeed