The first patient has been dosed in a Phase 2 trial testing an all-oral, triple-combination treatment that includes Cellcentric’s investigational therapy inobrodib in people with multiple myeloma who have failed prior treatments.
The DOMMINO-1 (NCT07096778) study will evaluate the efficacy and safety of a 20 mg dose of inobrodib in combination with two standard myeloma therapies — pomalidomide (sold as Pomalyst and generics) and dexamethasone — in a regimen called InoPd in people with relapsed or refractory multiple myeloma (RRMM), meaning their disease has returned or no longer responds to treatment.
The trial has begun treating patients at the Royal Marsden NHS Foundation Trust in London, and is enrolling up to 100 participants at additional sites in the U.K. and the U.S., the company said.
“Dosing the first patient in DOMMINO-1 marks an important milestone as we advance InoPd in registration-enabling studies,” Naseer Qayum, MD, PhD, chief strategy officer and head of research and development at Cellcentric, said in a company press release.
Myeloma is a type of blood cancer marked by the uncontrolled growth of plasma cells (a type of immune cell) in the bone marrow, the spongy tissue inside bones where blood cells are made.
‘New treatment options are urgently needed’
While patients are seeing better outcomes as a result of advances in treatment, “many people ultimately relapse or become refractory to these therapies, and new treatment options are urgently needed,” said Charlotte Pawlyn, MD, honorary consultant hematologist at the Royal Marsden NHS Foundation Trust and principal investigator for the study.
Given as an oral capsule, inobrodib targets p300 and CREB-binding protein (CBP), two proteins that together regulate the activity of key genes involved in cancer cell survival. By blocking these proteins, the therapy aims to limit myeloma cells’ ability to survive and grow.
“Inobrodib represents a novel mechanism through inhibition of p300/CBP and has demonstrated the ability to be used in combination with established therapies,” Pawlyn said. “We look forward to further evaluating InoPd in this trial.”
The therapy was evaluated in an earlier Phase 1/2a clinical trial (NCT04068597) involving more than 450 patients with multiple blood cancer types. In people with RRMM, inobrodib was tested both alone and in combination regimens, including with pomalidomide and dexamethasone.
In the Phase 2a dose-optimization portion, participants received 20 mg, 30 mg, or 40 mg of inobrodib in combination with standard doses of pomalidomide and dexamethasone. Results, recently shared by the company at a scientific conference, showed that among 44 evaluable patients at the time of the analysis, the overall response rate (ORR, or the proportion of patients whose cancer shrinks or disappears after treatment) was 69% in the 20 mg group. Response rates were lower at higher doses, with 54% in the 30 mg group and 33% in the 40 mg group.
In patients who had received at least five prior lines of therapy and whose disease no longer responded to pomalidomide, response rates reached 60% in the 20 mg group and 75% in the 30 mg group. These rates are substantially higher than those typically seen with certain currently available treatments in similar heavily pretreated patients, where real-world response rates are usually around 25% to 30%, according to the company.
Encouraging results
Data from the dose optimization study confirmed the favorable safety profile of InoPd. The combination was generally well tolerated at the 20 mg dose, with a safety profile consistent with pomalidomide and dexamethasone alone. Overall, the findings supported selecting the 20 mg dose for further evaluation in the ongoing DOMMINO-1 trial.
“Inobrodib 20 mg with [pomalidomide and dexamethasone] has demonstrated encouraging clinical activity, including a 60% objective response rate, and a tolerability profile consistent with [pomalidomide and dexamethasone] alone,” Qayum said. “We believe InoPd may deliver a transformative all-oral treatment for RRMM patients and look forward to further evaluating its potential in this Phase 2 trial.”
DOMMINO-1 is enrolling adults, ages 18 and older, whose disease is resistant to at least one proteasome inhibitor, one anti-CD38 antibody, and pomalidomide. Patients must also have been previously treated with a bispecific T-cell engager. These are lab-made antibodies that bring cancer cells into contact with T-cells (immune cells that can kill them), helping the immune system attack myeloma cells more effectively.
Participants will receive 20 mg of inobrodib by mouth twice daily for four days, followed by a three-day break, in repeated 28-day cycles. Inobrodib will be given alongside pomalidomide and dexamethasone, which will be administered according to standard schedules. Treatment will continue until the disease worsens, unacceptable side effects occur, or patients discontinue for other reasons.
The study’s main goal is to evaluate ORR. Secondary goals include changes in progression-free survival, or the length of time patients live without their disease getting worse, as well as overall survival and duration of response.
“InoPd appears to be a promising option in multiple myeloma treatment, not only for its tolerability and efficacy observed to date, but also for the practical benefits it may offer patients,” said Nisha Joseph, MD, associate professor at Emory University School of Medicine and a principal investigator for the DOMMINO-1 study at the first U.S. trial site. “More than 70% of patients are treated in the community setting, and an all-oral regimen may help expand access for those living with this disease, as well as their caregivers and healthcare providers.”
The post 1st patient dosed in trial of all-oral myeloma treatment combo appeared first on Rare Cancer News.