A Study to Find the Best Dose of BI 1387446 Alone or in Combination With Ezabenlimab (BI 754091) in Patients With Different Types of Advanced or Metastatic Cancer (Solid Tumors)

Phase 1

Completed

Conditions: Neoplasms

Interventions: Drug: BI 1387446 50 μg
Drug: BI 1387446 100 μg
Drug: BI 1387446 200 μg
Drug: BI 1387446 400 μg
Drug: BI 754091

Registration Number: NCT04147234

Lead Sponsor: Boehringer Ingelheim

Brief Summary: This is a study in adults with advanced cancer (solid tumours) in whom previous treatment was not successful. The study tests 2 medicines called BI 1387446 and BI 754091. Both medicines may help the immune system fight cancer. In this study, BI 1387446 is given to humans for the first time.

The purpose of this study is to find out the highest dose of BI 1387446 alone and in combination with BI 754091 the participants can tolerate. BI 1387446 is injected directly into the tumour.

Participants get BI 1387446 injections every week at the beginning and then every 3 weeks.

Some participants get BI 754091 in addition to BI 1387446. BI 754091 is given as an infusion into a vein every 3 weeks.

As long as they benefit from treatment and can tolerate it, participants can stay in the study for up to 2 years and 8 months. During this time, they visit the study site regularly. At these visit, doctors record any unwanted effects. The doctors also regularly check participants' health.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 42

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A: BI 1387446 50 μg	BI 1387446 50 μg	Participants were administered 50 μg of BI 1387446 intratumorally under visual inspection for visible skin tumors or under imaging guidance. The injection volume depended on tumor diameter.
Arm A: BI 1387446 100 μg	BI 1387446 100 μg	Participants were administered 100 μg of BI 1387446 intratumorally under visual inspection for visible skin tumors or under imaging guidance. The injection volume depended on tumor diameter.
Arm A: BI 1387446 200 μg	BI 1387446 200 μg	Participants were administered 200 μg of BI 1387446 intratumorally under visual inspection for visible skin tumors or under imaging guidance. The injection volume depended on tumor diameter.
Arm A: BI 1387446 400 μg	BI 1387446 400 μg	Participants were administered 400 μg of BI 1387446 intratumorally under visual inspection for visible skin tumors or under imaging guidance. The injection volume depended on tumor diameter.
Arm B: BI 1387446 50 μg / ezabenlimab 240 mg	BI 754091	Participants were administered 50 μg of BI 1387446 intratumorally under visual inspection for visible skin tumors or under imaging guidance. BI 754091 (ezabenlimab) was administered intravenously at the recommended phase II dose of 240 mg once every 3 weeks. The maximum duration of ezabenlimab treatment was 34 cycles. BI 1387446 injections were preferably performed after completing the ezabenlimab infusion.
Arm B: BI 1387446 100 μg / ezabenlimab 240 mg	BI 754091	Participants were administered 100 μg of BI 1387446 intratumorally under visual inspection for visible skin tumors or under imaging guidance. BI 754091 (ezabenlimab) was administered intravenously at the recommended phase II dose of 240 mg once every 3 weeks. The maximum duration of ezabenlimab treatment was 34 cycles. BI 1387446 injections were preferably performed after completing the ezabenlimab infusion.
Arm B: BI 1387446 200 μg / ezabenlimab 240 mg	BI 754091	Participants were administered 200 μg of BI 1387446 intratumorally under visual inspection for visible skin tumors or under imaging guidance. BI 754091 (ezabenlimab) was administered intravenously at the recommended phase II dose of 240 mg once every 3 weeks. The maximum duration of ezabenlimab treatment was 34 cycles. BI 1387446 injections were preferably performed after completing the ezabenlimab infusion.

Primary Outcome Measures

Name	Time	Method
Maximum Tolerated Dose (MTD) Based on Number of Dose-limiting Toxicities (DLTs)	From first administration of BI 1387446 until to end of treatment cycle 1 (up to 3 weeks).	The MTD in each arm is defined as the highest dose that is expected to cause less than 25% risk of the true DLT rate being above or equal to 33% during the MTD evaluation period. Estimation of the MTD will be based upon the estimation of the posterior probability of the incidence of DLT in toxicity categories during the MTD evaluation period for all evaluable participants. The MTD evaluation period is defined as the time from the first administration of any trial medication to the start of the second treatment cycle. Specifically, this is the time from the first dose to either the second administration of ezabenlimab or the fourth administration of BI 1387446, whichever occurs first. If the second dose of ezabenlimab or the fourth dose of BI 1387446 is not given, the evaluation period ends 90 days after the last administration.
Number of Patients With DLT in the MTD Evaluation Period	From first administration of BI 1387446 until to end of treatment cycle 1 (up to 3 weeks).	The MTD evaluation period is defined as the time from the first administration of any trial medication to the start of the second treatment cycle. Specifically, this is the time from the first dose to either the second administration of ezabenlimab or the fourth administration of BI 1387446, whichever occurs first. If the second dose of ezabenlimab or the fourth dose of BI 1387446 is not given, the evaluation period ends 90 days after the last administration.

Secondary Outcome Measures

Name	Time	Method
Objective Response Based on Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1)	From start of treatment up to the earliest of progression, death or end of trial (up to 1 year).	Objective response, as defined by the Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1), in accordance with Clinical Trial Protocol (CTP) Version 1 and 2, will be presented in terms of the objective response rate (ORR). The ORR is the proportion of patients whose best overall response is a confirmed complete response (CR) or partial response (PR). This determination is based on the investigator's assessment according to RECIST 1.1 criteria, from the date of the first treatment administration until the earliest occurrence of any of the following events: disease progression, death, the last evaluable tumor assessment before the initiation of subsequent anti-cancer therapy, loss to follow-up, or withdrawal of consent. Cross-over patients are shown in both Arm A (reflecting their initial treatment) and Arm B (reflecting their first treatment post-crossover). Their best overall response is counted, regardless of whether it occurred before or after the crossover.
Objective Response Based on Response Criteria for Intratumoural Immunotherapy in Solid Tumours (itRECIST)	From start of treatment up to the earliest of progression, death or end of trial (approximately 1 year).	Objective Response based on Response Criteria for Intratumoural Immunotherapy in Solid Tumours (itRECIST): (CTP version 3 and later) Objective response (OR) by itRECIST will be presented in terms of objective response rate (ORR), which is defined as the rate of patients whose best overall response is confirmed itCR or itPR as determined by the Investigator's assessment according to itRECIST from date of first treatment administration until the earliest of confirmed disease progression, death or last evaluable tumor assessment before start of subsequent anti-cancer therapy, loss to follow-up or withdrawal of consent. Cross-over patients are shown in both Arm A (reflecting their initial treatment) and Arm B (reflecting their first treatment post-crossover). Their best overall response is counted, regardless of whether it occurred before or after the crossover.
Best Percentage Change From Baseline in Size of Injected Lesions (CTP Version 1 or 2)	From start of treatment up to the earliest of progression, death or end of trial (approximately 1 year).	This endpoint evaluated the best percentage change (i.e., greatest reduction) in the size of injected lesions from baseline (the first measurement at the start of treatment) over time. The best percentage change from baseline in the size of injected lesions was analyzed using descriptive statistics. All lesion measurements recorded from the start of trial treatment until the earliest of the following were considered: disease progression (assessed under CTP v1 and v2 using RECIST 1.1), initiation of subsequent anti-cancer therapy, loss to follow-up, or withdrawal of consent. Cross-over patients appear in both Arm A (initial treatment) and Arm B (post-crossover treatment). Their best overall response is counted, regardless of timing. Negative values indicate a reduction in injected lesion diameters; positive values indicate an increase.
Best Percentage Change From Baseline in Size of Injected Target Lesions (CTP v3.0 or Later Versions)	From start of treatment up to the earliest of progression, death or end of trial (approximately 1 year).	This endpoint evaluated the best percentage change (i.e., greatest reduction) in the size of injected target lesions from baseline (the first measurement at the start of treatment) over time. The best percentage change from baseline in the size of injected target lesions was analyzed using descriptive statistics. All lesion measurements recorded from the start of trial treatment until the earliest of the following were considered: disease progression (assessed under CTP version 3 and later using itRECIST), initiation of subsequent anti-cancer therapy, loss to follow-up, or withdrawal of consent. Negative values indicate reduced lesion diameters; positive values indicate increases. Cross-over patients are included in Arm A (initial treatment) and Arm B (first post-crossover treatment), with their best response counted regardless of timing.
Best Percentage Change From Baseline in Size of Target Lesions (CTP Version 1 or 2)	From start of treatment until the earliest of progression, death or end of trial (approximately 1 year).	This endpoint evaluated the best percentage change (i.e., greatest reduction) in the size of target lesions from baseline (the first measurement at the start of treatment) over time. The best percentage change from baseline in the size of target lesions was analyzed using descriptive statistics. All lesion measurements recorded from the start of trial treatment until the earliest of the following were considered: disease progression (assessed under CTP v1 and v2 using RECIST 1.1), initiation of subsequent anti-cancer therapy, loss to follow-up, or withdrawal of consent. Cross-over patients appear in both Arm A (initial treatment) and Arm B (post-crossover treatment). Their best overall response is counted, regardless of timing. Negative values indicate a reduction in lesion diameters; positive values indicate an increase.
Best Percentage Change From Baseline in Size of Non-injected Target Lesions (CTP v3.0 or Later Versions)	From start of treatment until the earliest of progression, death or end of trial (approximately 1 year).	This endpoint evaluated the best percentage change (i.e., greatest reduction) in the size of non-injected target lesions from baseline (the first measurement at the start of treatment) over time. The best percentage change from baseline in the size of non-injected target lesions was analyzed using descriptive statistics. All lesion measurements recorded from the start of trial treatment until the earliest of the following were considered: disease progression (assessed under CTP version 3 and later using itRECIST), initiation of subsequent anti-cancer therapy, loss to follow-up, or withdrawal of consent.

Trial Locations

Locations (8): The University of North Carolina at Chapel Hill
🇺🇸
Chapel Hill, North Carolina, United States
Hospital Vall d'Hebron
🇪🇸
Barcelona, Spain
Froedtert and The Medical College of Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States
CIO Clara Campal
🇪🇸
Madrid, Spain
Hospital Clínico de Valencia
🇪🇸
Valencia, Spain
The Royal Marsden Hospital, Chelsea
🇬🇧
London, United Kingdom
Churchill Hospital
🇬🇧
Oxford, United Kingdom
The Royal Marsden Hospital, Sutton
🇬🇧
Sutton, United Kingdom
The University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States