A Study in People With Colorectal Cancer to Test Whether Ezabenlimab or Pembrolizumab in Combination With BI 765063 Lead to Side Effects or Delays in Surgery

Study Overview
=================
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.

Official Title
-----------------
A Phase I Open Label Study to Assess Safety, Feasibility, Efficacy, and Biological Activity of Single Administration of Neoadjuvant Treatments Ezabenlimab in Combination With BI 765063 and Pembrolizumab in Combination With BI 765063 in Patients With Newly Diagnosed Surgically-resectable, Locoregional Colorectal Cancer

Conditions
-----------------
Colorectal Cancer

Intervention / Treatment
-----------------
* Drug: Ezabenlimab
* Drug: BI 765063
* Drug: Pembrolizumab


Participation Criteria
=================
Eligibility Criteria
-----------------
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 exclusion criteria apply

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A: Ezabenlimab + BI 765063<br> | Drug: Ezabenlimab<br>* Ezabenlimab<br>Drug: BI 765063<br>* BI 765063<br>|
| Experimental: Cohort B: Pembrolizumab + BI 765063<br> | Drug: BI 765063<br>* BI 765063<br>Drug: Pembrolizumab<br>* Pembrolizumab<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite endpoint: Proportion of patients with at least one occurrence of a safety or feasibility event | Safety is defined as any grade 3 or higher adverse events (according to NCI Common Terminology Criteria for Adverse Event (CTCAE) v5.0) related to study treatments at any point within the follow up period following the administration of study treatments. Feasibility or delay in surgery is defined as any treatment related adverse events leading to delay in surgery. | up to 91 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological response | Pathological response defined as 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. | up to 91 days | 
| 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 |  | up to 91 days | 
| Radiographic response on pre-surgical imaging, following receipt of the neoadjuvant therapy, as per response evaluation criteria in solid tumors (RECIST) v1.1 |  | up to 91 days |