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)

Boehringer Ingelheim42 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Neoplasms

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion criteria * Histologically or cytologically confirmed diagnosis of an advanced, unresectable and/or metastatic malignant solid tumor and indication for treatment * Patient must have exhausted established treatment options known to prolong survival for the malignant disease, or is not eligible for established treatment options. * Medically fit and willing to undergo all mandatory trial procedures. * At least one tumor lesion which is suitable for injection (Screening/initial administration), appropriate for the allocated treatment arm, and measurable. * At least 1 discrete lesion, in addition to the lesion proposed for injection, which is amenable to biopsy and is not located in the brain, mediastinum or pancreas. * Adequate organ function or bone marrow reserve * Further inclusion criteria apply Exclusion criteria: * Any investigational or antitumour treatment (including antibodies targeting Programmed Cell Death-1 (PD1) - or programmed Death-Ligand 1 (PDL1)) within 4 weeks or 5 half-life periods (whichever is shorter) prior to the initial administration of BI 1387446 or BI 754091. * Persistent toxicity from previous treatments (including Immune-related Adverse Events (irAEs)) that has not resolved to ≤ Grade 1, except for alopecia, xerostomia, and immunotherapy related endocrinopathies which may be included if clinically stable on hormone supplements or antidiabetic drugs as per Investigator judgement * History or evidence of active, non-treatment related autoimmune disease, except for endocrinopathies which may be included if clinically stable on hormone supplements or antidiabetic drugs. * History or evidence of pneumonitis related to prior immunotherapy * Immunosuppressive corticosteroid doses (\>10 mg prednisone daily or equivalent) within 2 weeks prior to the first dose of BI 1387446 or BI 754091. * The tumor at the projected injection site has a high risk for local complications, e.g. bleeding related to encasement/infiltration of major blood vessels or contact with liver capsule, compression of vital structures in case of swelling of injected lesion, in the opinion of the Investigator. * Active infection requiring systemic therapy at the start of treatment in the trial, including active viral hepatitis infection or active tuberculosis infection. * Cardiac insufficiency New York Heart Association (NYHA) III or IV * Left ventricular ejection fraction \< 50% measured by echocardiography or Multigated Acquisition (MUGA) scan * Mean resting corrected QT interval (QTc) \>470 msec * Further exclusion criteria apply

Outcomes

Primary Outcomes

Maximum Tolerated Dose (MTD) Based on Number of Dose-limiting Toxicities (DLTs)

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.

Time frame: From first administration of BI 1387446 until to end of treatment cycle 1 (up to 3 weeks).

Number of Patients With DLT in the MTD Evaluation Period

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.

Time frame: From first administration of BI 1387446 until to end of treatment cycle 1 (up to 3 weeks).

Secondary Outcomes

Objective Response Based on Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1)

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.

Time frame: From start of treatment up to the earliest of progression, death or end of trial (up to 1 year).

Objective Response Based on Response Criteria for Intratumoural Immunotherapy in Solid Tumours (itRECIST)

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.

Time frame: From start of treatment up to the earliest of progression, death or end of trial (approximately 1 year).

Best Percentage Change From Baseline in Size of Injected Lesions (CTP Version 1 or 2)

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.

Time frame: From start of treatment up to the earliest of progression, death or end of trial (approximately 1 year).

Best Percentage Change From Baseline in Size of Injected Target Lesions (CTP v3.0 or Later Versions)

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.

Time frame: From start of treatment up to the earliest of progression, death or end of trial (approximately 1 year).

Best Percentage Change From Baseline in Size of Target Lesions (CTP Version 1 or 2)

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.

Time frame: From start of treatment until the earliest of progression, death or end of trial (approximately 1 year).

Best Percentage Change From Baseline in Size of Non-injected Target Lesions (CTP v3.0 or Later Versions)

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.

Time frame: From start of treatment until the earliest of progression, death or end of trial (approximately 1 year).

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)

Overview

Conditions

Interventions

Eligibility

Locations (8)

Outcomes

Primary Outcomes

Secondary Outcomes