MSI-H Colorectal CancerPhase 2NCT06006923
Regorafenib in Combination With Pembrolizumab or Pembrolizumab for MSI-H Colorectal Cancer
A Phase 2 study testing Regorafenib and Pembrolizumab in people with MSI-H Colorectal Cancer, run by Anwaar Saeed at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- MSI-H Colorectal Cancer
- What is being tested?
- Regorafenib and Pembrolizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Jun 2024to 12 Nov 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed mismatch repair deficient or microsatellite instability high advanced stage colorectal cancer
- Measurable disease (per RECIST v1.1)
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
- Age > 18
- The patient must be able to swallow oral medication.
- Adequate organ function based on the following lab assessments:
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- ANC must be ≥ 1500/mm3
- platelet count must be ≥ 100,000/mm3
- WBC count ≥ 2.5 × 109 /L
- Hemoglobin must be ≥ 9 g/dL
- Alkaline phosphatase ≤ 2.5× upper limit of normal (ULN) with the exception of patients with documented liver or bone metastases who should have ALP ≤ 5.0× ULN
- AST and ALT ≤ 2.5× ULN with the exception of patients with documented liver metastases who may have AST and/or ALT ≤ 5.0× ULN
- International normalized ratio (INR) ≤ 1.5 x ULN and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless receiving treatment with therapeutic anticoagulation
- Total bilirubin ≤ 1.5× ULN (≤ 3× ULN if Gilbert syndrome present)
- Serum albumin ≥ 2.8 g/dL or 28 g/L
- Creatinine clearance ≥ 50 mL/min (calculated using the Cockcroft-Gault formula) or creatinine ≤ 1.5× ULN
- No more than three cycles of prior fluoropyrimidine-based chemotherapy including folinic acid, fluorouracil, and oxaliplatin (FOLFOX); folinic acid, fluorouracil, and irinotecan (FOLFIRI); and, folinic acid, fluorouracil, oxaliplatin, and irinotecan (FOLFOXIRI) excluding adjuvant treatment
- Patients (male or female) of reproductive potential must agree to use an effective method of contraception (as discussed with treating physician) from the time consent is signed, during study therapy, and for at least 8 weeks after the last dose of study therapy.
- Patients who received no more than 1 cycle of pembrolizumab monotherapy will be still eligible to be enrolled in lead in phase of the trial
Who cannot join
- Prior anti-programmed death 1 (anti-PD-1) or anti-cytotoxic T-lymphocyte-associated antigen 4 (anti-CTLA-4) based therapy
- More than 3 cycles of chemotherapy or progression of disease on first line therapy excluding adjuvant treatment and any systemic anticancer treatment within 2 weeks or 5 half-lives (whichever is shorter) prior to start of study treatment
- Active autoimmune disease
- Pregnant or lactating females
- Uncontrolled human immunodeficiency virus (HIV), hepatitis B virus (HBV), and/or hepatitis C virus (HCV); patients with undetectable viral load and CD4 count > 200 will be eligible for enrollment
- Active untreated brain metastasis
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- Uncontrolled hypertension (HTN: systolic pressure > 150 mmHg or diastolic pressure > 90 mmHg on repeated measurements) and cardiovascular events within 12 months of start of treatment
- Active infection or chronic infection requiring chronic suppressive antibiotics
- No active cancer such as colon cancer other than adenocarcinoma (e.g., sarcoma, lymphoma, carcinoid) within 1 year
- Patients with severe hepatic impairment (Child-Pugh C) are excluded as regorafenib has not been studied in this population and exposure might be increased in these patients
- Major surgical procedure or significant traumatic injury within 28 days before start of study medication
- Non-healing wound, non-healing ulcer, or non-healing bone fracture
- Patients with evidence or history of any bleeding diathesis, irrespective of severity
- Any hemorrhage or bleeding event ≥ CTCAE Grade 3 within 4 weeks prior to the start of study medication:
- Major surgical procedure or significant traumatic injury within 28 days before start of study medication
- Non-healing wound, non-healing ulcer, or non-healing bone fracture
- Patients with evidence or history of any bleeding diathesis, irrespective of severity
- Any hemorrhage or bleeding event ≥ CTCAE Grade 3 within 4 weeks prior to the start of study medication
Trial locations and contacts
1 site in 1 country.
United States1 site
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
About this study
Official title: Randomized Trial of Regorafenib in Combination With Pembrolizumab or Pembrolizumab Monotherapy With an Efficacy Lead-in of Regorafenib and Pembrolizumab for Patients With MSI-H Colorectal Cancer
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.
Read the detailed description
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.
- Conditions
- MSI-H Colorectal Cancer
- Being tested
- Regorafenib, Pembrolizumab
- Keywords
- multi-kinase inhibitor, receptor tyrosine kinases, anti-PD1 blockade, immune checkpoint inhibitor, vascular endothelial growth factor receptor (VEGFR)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RegorafenibDrug
Also called BAY 73-4506, Stivarga
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.
PembrolizumabDrug
Also called Keytruda
An anti-PD1 blockade / immune checkpoint inhibitor treatment approved for patients with high microsatellite instability (MSI-H) colorectal cancer (CRC) as first line therapy.
| Study group | Role | What they receive |
|---|---|---|
| Pembrolizumab + Regorafenib | Experimental | Pembrolizumab: 200mg, Q3 weeks
Regorafenib: 60mg Cycle 1 Day 1 90 mg Cycle 2 Day 1 Receives: Drug: Regorafenib; Drug: Pembrolizumab |
| Pembrolizumab | Active comparator | Pembrolizumab: 200mg, Q3 weeks Receives: Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Up to 24 months
Secondary outcomes (6)
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.
Measured: 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.
Measured: 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.
Measured: Up to 24 months
Overall Survival (OS)
Median number of months from start of treatment to death from any cause.
Measured: Up to 48 months (lead-in phase)
Overall Survival (OS)
Median number of months from time of randomization to death from any cause.
Measured: 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.
Measured: Up to 12 months (beginning at start of post lead-in phase)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Aug 2023
- Study start26 Jun 2024
- Primary completion11 Jul 2025
- Study completion12 Nov 2025
Why it stopped: Terminated per directive from Bayer due to funding.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MSI-H Colorectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Anwaar Saeed
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer
- Responsible party
- Sponsor-investigator, Anwaar Saeed, University of Pittsburgh
- Investigators
- Anwaar H Saeed, MD, Principal investigator, UPMC Hillman Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06006923
- Sponsor's protocol ID
- HCC 23-041
- Status last verified
- Jan 2026
- First submitted
- 17 Aug 2023
- Last updated
- 20 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Trial of Regorafenib in Combination With Pembrolizumab or Pembrolizumab Monotherapy With an Efficacy Lead-in of Regorafenib and Pembrolizumab for Patients With MSI-H Colorectal Cancer
- ClinicalTrials.gov ID
- NCT06006923
- Acronym / sponsor ID
- HCC 23-041
- Conditions
- MSI-H Colorectal Cancer
- Keywords
- multi-kinase inhibitor, receptor tyrosine kinases, anti-PD1 blockade, immune checkpoint inhibitor, vascular endothelial growth factor receptor (VEGFR)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Terminated per directive from Bayer due to funding.
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Anwaar SaeedUniversity, hospital or other
- Collaborators
- Bayer
- Study start
- 26 Jun 2024 (actual)
- Primary completion
- 11 Jul 2025 (actual)
- Study completion
- 12 Nov 2025 (actual)
- First posted
- 23 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab + Regorafenib | Experimental | Drug: Regorafenib, Drug: PembrolizumabPembrolizumab: 200mg, Q3 weeks Regorafenib: 60mg Cycle 1 Day 1 90 mg Cycle 2 Day 1 |
| Pembrolizumab | Active comparator | Drug: PembrolizumabPembrolizumab: 200mg, Q3 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Histologically confirmed mismatch repair deficient or microsatellite instability high advanced stage colorectal cancer
- Measurable disease (per RECIST v1.1)
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
- Age > 18
- The patient must be able to swallow oral medication.
Key exclusion criteria (18 listed)
- Prior anti-programmed death 1 (anti-PD-1) or anti-cytotoxic T-lymphocyte-associated antigen 4 (anti-CTLA-4) based therapy
- More than 3 cycles of chemotherapy or progression of disease on first line therapy excluding adjuvant treatment and any systemic anticancer treatment within 2 weeks or 5 half-lives (whichever is shorter) prior to start of study treatment
- Active autoimmune disease
- Pregnant or lactating females
- Uncontrolled human immunodeficiency virus (HIV), hepatitis B virus (HBV), and/or hepatitis C virus (HCV); patients with undetectable viral load and CD4 count > 200 will be eligible for enrollment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RegorafenibAlso: BAY 73-4506, StivargaA 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. | Drug | Pembrolizumab + Regorafenib |
| PembrolizumabAlso: KeytrudaAn anti-PD1 blockade / immune checkpoint inhibitor treatment approved for patients with high microsatellite instability (MSI-H) colorectal cancer (CRC) as first line therapy. | Drug | Pembrolizumab, Pembrolizumab + Regorafenib |
Primary outcome
Objective Response Rate (ORR), Lead-in Phase
Time frame: Up to 12 months (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.
Progression-free Survival (PFS), Randomize Phase
Time frame: Up to 24 months
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.
6 secondary outcomes
Adverse Events and Serious Adverse Events Related to Treatment
Time frame: Up to 24 months (lead-in phase)
Adverse Events and Serious Adverse Events Related to Treatment
Time frame: Up to 24 months (beginning at start of post lead-in phase)
Progression-free Survival (PFS), Lead-In Phase
Time frame: Up to 24 months
Overall Survival (OS)
Time frame: Up to 48 months (lead-in phase)
Overall Survival (OS)
Time frame: Up to 24 months (beginning at start of post lead-in phase)
Objective Response Rate (ORR), Randomized Phase
Time frame: Up to 12 months (beginning at start of post lead-in phase)
Results and safety
The study was stopped early (reason given: Terminated per directive from Bayer due to funding.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jan 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anwaar H Saeed, MD principal investigator
UPMC Hillman Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Regorafenib and Pembrolizumab in people with MSI-H Colorectal Cancer, run by Anwaar Saeed at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 20 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Terminated per directive from Bayer due to funding.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR), Lead-in Phase (time frame: Up to 12 months (lead-in phase)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jan 2026.