Long-term Safety Evaluation of Oral Brigimadlin Monotherapy in Patients with Solid Tumors: A Phase II, Single-Arm, Open-Label Rollover Study

The primary objective of this Phase II, single-arm, open-label, long-term safety rollover trial is to evaluate the long-term **safety** and **tolerability** of brigimadlin monotherapy in patients with solid tumors who have previously participated in another trial within the brigimadlin program. This will be achieved by assessing the incidence of treatment-emergent adverse events (AEs) and characterizing their severity, frequency, seriousness, relationship to the treatment, and outcomes. Understanding the long-term safety profile of brigimadlin is clinically relevant as it informs the risk-benefit assessment for its continued use in patients with solid tumors.

The clinical trial involves a total of **53 participants** who have previously participated in another trial within the brigimadlin program. The study population includes both **male and female subjects** and spans an **age range** that includes adults and older adults. Participants are individuals with **solid tumors** and are required to have adequate organ function. The trial does not include a vulnerable population. Participants were selected based on their ongoing or qualifying status for crossover to brigimadlin treatment in any trial sponsored by Boehringer Ingelheim. Relevant lifestyle considerations include adherence to contraceptive guidelines and compliance with scheduled visits, treatment plans, and other study procedures. The trial population is characterized by the resolution of toxicities related to previous anti-cancer therapies to a manageable level, except for specific conditions such as alopecia and amenorrhea, which can be of any grade, and peripheral neuropathy, which must be of a lower grade. The sponsor has not provided additional information regarding specific lifestyle factors such as diet or physical activity.

The clinical trial is designed as a **Phase II**, single-arm, open-label, long-term safety rollover study to evaluate the safety and tolerability of **brigimadlin** monotherapy in patients with **solid tumors**. The trial will assess the incidence of treatment-emergent adverse events (AEs) and characterize their severity, frequency, seriousness, relationship, and outcome. Participants eligible for this trial are those who are ongoing on brigimadlin treatment or qualify for crossover to brigimadlin treatment in any trial sponsored by Boehringer Ingelheim, referred to as the 'parent trial'. The trial is expected to commence recruitment on December 9, 2024, and is estimated to conclude by December 31, 2036.

The trial involves a sequence of study visits, beginning with an inclusion (screening) visit where eligibility is confirmed based on criteria such as ongoing treatment with brigimadlin, provision of informed consent, and adequate organ function. Participants must also comply with contraceptive guidelines and have resolved toxicities from previous therapies to a specified grade. Follow-up visits will be conducted to monitor the occurrence of treatment-emergent AEs according to CTCAE Version 5.0 throughout the treatment period. The end-of-study visit will mark the conclusion of the participant's involvement, which is expected to last up to 60 days, corresponding to the maximum treatment period.

Participants will be administered brigimadlin in the form of a **film-coated tablet** for **oral use**, with a maximum daily dose of 30 mg or 45 mg, depending on the specific product formulation. The total dose will not exceed 2610 mg or 3915 mg over the treatment period. Conditions that may lead to early termination from the study include non-compliance with the treatment plan, lifestyle, laboratory tests, or other study procedures, as well as the occurrence of severe adverse events that necessitate discontinuation of the treatment. The trial is not categorized as low intervention and is conducted to investigate the long-term safety of brigimadlin in patients with solid tumors.

The clinical trial involves the administration of the experimental medication **BI 907828**, which is provided in the form of a **film-coated tablet**. The active substance in BI 907828 is chemically derived and identified as (3S,3'S,3A'S,10A'S)-6-chloro-3'-(3-chloro-2-fluorophenyl)-1'-(cyclopropylmethyl)-6'-methyl-2-oxo-1,2,3',3A',10',10A'-hexahydro-1'H-spiro[indole-3,2'-pyrrolo[2',3':4,5]pyrrolo[1,2-b]indazole]-7'-carboxylic acid. The medication is administered orally, with a maximum daily dose of 30 mg for some participants and 45 mg for others, depending on the specific protocol requirements. The total maximum dose over the treatment period is 2610 mg or 3915 mg, respectively, with a treatment duration of up to 60 days.

BI 907828 is an orphan drug, designated under the number EU/3/23/2792, and is not formulated for pediatric use. The trial aims to evaluate the long-term safety and tolerability of BI 907828 monotherapy in patients with solid tumors. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen. No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are utilized in this study. The trial is conducted under the sponsorship of Boehringer Ingelheim International, with the product authorized for use in this clinical setting.

The efficacy of the clinical trial will be assessed primarily through the occurrence of treatment-emergent **Adverse Events (AEs)**, as defined by the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. This assessment will be conducted throughout the entire treatment period. The primary endpoint focuses on evaluating the incidence, severity, frequency, seriousness, relationship, and outcome of these treatment-emergent AEs. The trial is designed to monitor the long-term safety and tolerability of brigimadlin monotherapy in patients with solid tumors who have previously participated in another trial within the brigimadlin program. The data collection will be ongoing, with the estimated end date of the trial set for December 31, 2036. The trial will ensure that all toxicities related to previous anti-cancer therapies have resolved to CTCAE Grade ≤1 prior to trial treatment administration, except for alopecia and amenorrhea/menstrual disorders, which can be any grade, and peripheral neuropathy, which must be CTCAE Grade ≤2.