Trial Participants: This trial will include an estimated number of 35 participants with melanoma cancer who have not been helped by standard treatments.
The main purposes of this trial are :
1. To learn about the safety and tolerability of BI1607 when received in combination with ipilimumab and pembrolizumab,
2. To determine the best dose (quantity) of both BI-1607 and ipilimumab when combined with pembrolizumab, and
3. To see if this triple combination therapy of BI-1607/ipilimumab/ pembrolizumab is more effective.
To investigate this, the researchers will study:
* what medical problems can happen during the trial, whether there are changes in the participants' health, how many participants reduce their dose of treatment or stop treatment for a period during the trial, and how many participants have medical problems that cause them to stop their trial treatment early.
* how many participants have dose-limiting toxicities (also called "DLTs", which are medical problems severe enough to stop the trial doctors from increasing a treatment dose in the next group of participants).
2\. The researchers will also study the following additional questions in this trial:
* how BI-1607 acts in the body when received with ipilimumab/pembrolizumab.
* whether the triple combination at varying doses of BI-1607 and ipilimumab acts in the participants' bodies as expected and has a desired effect on certain proteins in the participants' immune systems.
* the number of participants who produce "antibodies" against BI-1607 and tolerability. Antibodies are proteins which are part of the immune system that help fight an infection. However, the body can produce antibodies against a treatment, which can stop the treatment from working properly.
* how many participants' tumors shrink after receiving BI-1607 in combination with ipilimumab/pembrolizumab, and how long do their tumors shrink before their melanoma get worse or they pass away.
What is planned to happen during this trial: The participants are planned to be in this trial for a maximum of 25.5 months. This trial started end of 2024 and is planned to end in 2028.
This trial will have 2 parts, called Phase 1 and Phase 2.
In Phase 1, at least 15 participants will receive BI-1607 and ipilimumab once every three weeks over four treatment time points, i.e., 12 weeks. Pembrolizumab will be added to the combination treatment at the third and fourth treatment. If the participant continues in the trial thereafter, pembrolizumab will be administered alone every third week from the fifth week onwards, up to a total of 35 treatments or approximately 2 years. This phase 1 will likely contain 4 groups of participants receiving different dose levels of treatments. After the participants in the first dose group have received their first treatments, the Sponsor, in collaboration with researchers, decides if this dose is safe, and the dose will be increased in the next group of participants.
In Phase 2, approximately 20 participants will receive BI-1607 at the selected dose that the Sponsor and researchers decide is safe during Phase 1. BI-1607 will be administered once every three weeks in combination with both ipilimumab and pembrolizumab over four treatment time points, i.e., 12 weeks. Thereafter, pembrolizumab will be administered alone every third week, up to a total of 35 treatments or approximately 2 years.
In both phases, the treatments will be administered via an "IV infusion" in which an IV line is inserted into a vein usually in the arm. The treatments will be dosed in milligrams, also called "mg". The lowest dose of BI-1607 will be 350 mg, and the highest possible dose will be 700 mg. Ipilimumab will be given to participants at a dose of 1 mg/kg body weight or 3 mg/kg. The dose of pembrolizumab will be 200 mg.
Throughout the trial, the researchers will check the participants' health and any medical problems, ask about any medications they are receiving, take blood, tumor, and urine samples, and scan their tumors. The researchers will do these tests to learn how safe BI-1607 is in combination with ipilimumab/pembrolizumab, how the drug acts in the body, and how the treatment affects the participants' tumors.
Benefits of this trial: There is no guarantee that the participants will receive any benefit from participating in this trial. However, their participation may help other people who have melanoma receive better care in the future.
Risks of this trial: Participant safety is the most important factor in clinical trials. However, it cannot be guaranteed that the participants will not have medical problems during this trial. The clinical researcher will determine if the participant should no longer take part in the study if the results show the treatment doses are not safe. The Sponsor, Ethics Committee, or Regulatory Authority may also decide to stop the study at any time for any reason.
