Colorectal Cancer
Conditions
Brief summary
This study is open to people with newly diagnosed colorectal cancer. People who are scheduled for surgery can participate. People either get a medicine called BI 765063 combined with ezabenlimab or combined with pembrolizumab in preparation of the upcoming surgery. The tested medicines in this study are antibodies that may help the immune system fight cancer. The purpose of this study is to find out how well people with early colorectal cancer can tolerate treatment with these medicines. The study also looks at whether the tumor changes. Participants are put into 2 groups. One group gets ezabenlimab and BI 765063. The other group gets pembrolizumab and BI 765063. All participants receive the study medicines as 2 subsequent infusions into a vein on a single day. Participants are in the study for about 4 months. During this time, they visit the study site about 5 times. The doctors check the health of the participants and note any health problems that could have been caused by ezabenlimab, pembrolizumab, or BI 765063. The doctors also check whether these health problems lead to a delay of the planned surgery.
Interventions
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial. Ability to understand and the willingness to sign a written informed consent. * Male or female aged = 18 years at the time of informed consent form (ICF) signature. * Patients with histological diagnosis of resectable colorectal Cancer (CRC), or radiographic/visual findings highly suggestive, with planned confirmatory biopsy. * CRC lesions must be at least 1 centimeter (cm) in largest diameter and amenable to endoscopic biopsy. * Patient must be willing and able to have endoscopic biopsy (Goal 3-6 core-needle or surgical/endoscopic biopsies, final number to be determined by the physician performing the procedure as safe) of tumor prior to initiation of therapy. * Eastern Cooperative Oncology Group (ECOG) performance status 0-1. The exception will be patients with long term disability (such as cerebral palsy) that is unlikely to significantly affect their response to therapy. * Patient is determined to be a surgical candidate for resection of their tumor. * Adequate organ and marrow function as defined in the protocol. * Further inclusion criteria apply.
Exclusion criteria
* Patients who are deemed to be at high risk for colonic obstruction and/or perforation per investigator assessment. * Patients eligible for neoadjuvant therapy (chemotherapy, radiotherapy, chemoradiotherapy) as standard of care. * Major surgery (major according to the investigator's assessment) performed within 4 weeks prior to administration of trial medication. * Patients who must or wish to continue the intake of restricted medications (as defined in the protocol) or any drug considered likely to interfere with the safe conduct of the trial. * Patients not expected to comply with the protocol requirements or not expected to complete the trial as scheduled (e.g. chronic alcohol or drug abuse or any other condition that, in the investigator's opinion, makes the patient an unreliable trial participant). * Previous enrolment in this trial. * Currently enrolled in another investigational device or drug trial, or less than 30 days since ending another investigational device or drug trial(s) or receiving other investigational treatment(s). * Patients who have had chemotherapy or radiotherapy within 6 months prior to entering the study for a different primary tumor, or those that have received locoregional therapy (radiation, chemoembolization, etc.) for the target lesion that will be biopsied and subsequently resected. Previous therapy for a different cancer (a different primary) is acceptable. * Prior immune checkpoint inhibitor therapy. * Patients with metastatic or recurrent disease, for which the intent of surgery would not be curative. * Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite Endpoint: Proportion of Patients With at Least One Occurrence of a Safety or Feasibility Event | Up to 91 days after drug administration. | Safety: A safety event was defined as any grade 3 or higher adverse events (AEs; according to National Cancer Institute's Common Terminology Criteria for Adverse Events \[CTCAE\] version 5.0) related to study treatments at any point within the follow-up period following the administration of study treatments. Feasibility (delay in surgery): A feasibility event or delay in surgery was defined as any treatment related AE leading to delay in surgery, which was scheduled to take place between 2 weeks and up to 6 weeks following the study treatment administration will be considered as a relevant AE for this endpoint. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pathologic Response (PR) | Up to 91 days after drug administration. | At least 50% or more tumor regression classified as per Mandard tumor regression grading system, in viable adenocarcinoma cells in the surgical specimen, including lymph nodes. Pathological response includes complete pathology response (CR), near complete pathological response (near CR) and partial pathological response |
| Time From Administration of Trial Treatment to Surgery | Up to 91 days after drug administration. | Time from administration of trial treatment to surgery, defined as the time in days that elapses between administration of neoadjuvant trial therapy and surgical resection. |
| Radiographic Response Rate | Up to 91 days after drug administration. | Radiographic response on pre-surgical imaging, following receipt of the neoadjuvant therapy, as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). The same imaging procedure(s) (computed tomography, magnetic resonance imaging scan) were used throughout the trial. |
Countries
United States
Participant flow
Recruitment details
An open-label, single-center, two-arm, parallel-group Phase I trial to assess the safety and feasibility of a single dose of BI 765063 in combination with either ezabenlimab (Cohort A) or pembrolizumab (Cohort B) in participants with early-stage, resectable colorectal cancer in a neoadjuvant setting.
Pre-assignment details
Only two participants were enrolled in this trial. All participants were screened for eligibility prior to participation and attended a specialist site to ensure strict adherence to all inclusion criteria and none of the exclusion criteria. Participants were not allocated to a treatment group if any entry criteria were violated. The trial was prematurely discontinued due to the low number of enrolled participants.
Participants by arm
| Arm | Count |
|---|---|
| Cohort A: Ezabenlimab + BI 765063 Participants received two separate consecutive intravenous (i.v.) infusions on Day 1. First, they received one flat dose of 240 milligram (mg) ezabenlimab and then one dose of BI 765063. | 1 |
| Cohort B: Pembrolizumab + BI 765063 Participants received two separate consecutive intravenous (i.v.) infusions on Day 1. First, they received one flat dose of 200 milligram (mg) Pembrolizumab and then one dose of BI 765063. | 1 |
| Total | 2 |
Baseline characteristics
| Characteristic | Cohort B: Pembrolizumab + BI 765063 | Total | Cohort A: Ezabenlimab + BI 765063 |
|---|---|---|---|
| Age, Customized >= 18 years | 1 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 1 |
| other Total, other adverse events | 1 / 1 | 1 / 1 |
| serious Total, serious adverse events | 0 / 1 | 0 / 1 |
Outcome results
Primary
Composite Endpoint: Proportion of Patients With at Least One Occurrence of a Safety or Feasibility Event
Safety: A safety event was defined as any grade 3 or higher adverse events (AEs; according to National Cancer Institute's Common Terminology Criteria for Adverse Events \[CTCAE\] version 5.0) related to study treatments at any point within the follow-up period following the administration of study treatments. Feasibility (delay in surgery): A feasibility event or delay in surgery was defined as any treatment related AE leading to delay in surgery, which was scheduled to take place between 2 weeks and up to 6 weeks following the study treatment administration will be considered as a relevant AE for this endpoint.
Time frame: Up to 91 days after drug administration.
Population: The trial was discontinued early due to slow participant enrollment. Only a patient profile listing containing data collected for individual participants was compiled and statistical outputs and analyses i.e. the primary and secondary outcome measurements were not assessed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ezabenlimab + BI 765063 | Composite Endpoint: Proportion of Patients With at Least One Occurrence of a Safety or Feasibility Event | 0 Percentage of Participants |
| Pembrolizumab + BI 765063 | Composite Endpoint: Proportion of Patients With at Least One Occurrence of a Safety or Feasibility Event | 0 Percentage of Participants |
Secondary
Pathologic Response (PR)
At least 50% or more tumor regression classified as per Mandard tumor regression grading system, in viable adenocarcinoma cells in the surgical specimen, including lymph nodes. Pathological response includes complete pathology response (CR), near complete pathological response (near CR) and partial pathological response
Time frame: Up to 91 days after drug administration.
Population: The trial was discontinued early due to slow participant enrollment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ezabenlimab + BI 765063 | Pathologic Response (PR) | Complete pathology response (CR) | 0 Percentage of Participants |
| Ezabenlimab + BI 765063 | Pathologic Response (PR) | Near complete pathological response (near CR) | 0 Percentage of Participants |
| Ezabenlimab + BI 765063 | Pathologic Response (PR) | Partial pathological response | 0 Percentage of Participants |
| Ezabenlimab + BI 765063 | Pathologic Response (PR) | No response | 1 Percentage of Participants |
| Pembrolizumab + BI 765063 | Pathologic Response (PR) | No response | 1 Percentage of Participants |
| Pembrolizumab + BI 765063 | Pathologic Response (PR) | Complete pathology response (CR) | 0 Percentage of Participants |
| Pembrolizumab + BI 765063 | Pathologic Response (PR) | Partial pathological response | 0 Percentage of Participants |
| Pembrolizumab + BI 765063 | Pathologic Response (PR) | Near complete pathological response (near CR) | 0 Percentage of Participants |
Secondary
Radiographic Response Rate
Radiographic response on pre-surgical imaging, following receipt of the neoadjuvant therapy, as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). The same imaging procedure(s) (computed tomography, magnetic resonance imaging scan) were used throughout the trial.
Time frame: Up to 91 days after drug administration.
Population: The trial was discontinued early due to slow participant enrollment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ezabenlimab + BI 765063 | Radiographic Response Rate | Complete Response (CR) | 0 Percentage of participants |
| Ezabenlimab + BI 765063 | Radiographic Response Rate | Partial Response (PR) | 0 Percentage of participants |
| Ezabenlimab + BI 765063 | Radiographic Response Rate | Progressive Disease (PD) | 0 Percentage of participants |
| Ezabenlimab + BI 765063 | Radiographic Response Rate | Stable Disease (SD) | 100 Percentage of participants |
| Pembrolizumab + BI 765063 | Radiographic Response Rate | Stable Disease (SD) | 100 Percentage of participants |
| Pembrolizumab + BI 765063 | Radiographic Response Rate | Complete Response (CR) | 0 Percentage of participants |
| Pembrolizumab + BI 765063 | Radiographic Response Rate | Progressive Disease (PD) | 0 Percentage of participants |
| Pembrolizumab + BI 765063 | Radiographic Response Rate | Partial Response (PR) | 0 Percentage of participants |
Secondary
Time From Administration of Trial Treatment to Surgery
Time from administration of trial treatment to surgery, defined as the time in days that elapses between administration of neoadjuvant trial therapy and surgical resection.
Time frame: Up to 91 days after drug administration.
Population: The trial was discontinued early due to slow participant enrollment.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Ezabenlimab + BI 765063 | Time From Administration of Trial Treatment to Surgery | 19 days |
| Pembrolizumab + BI 765063 | Time From Administration of Trial Treatment to Surgery | 19 days |