Neeta Somaiah, MD, associate professor, deputy department chair, Department of Sarcoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses enrollment criteria for the phase 3 Peak trial (NCT05208047) in patients with gastrointestinal stromal tumor (GIST) and the advantages of this trial’s design.

The Peak trial is investigating bezuclastinib (CGT9486) in combination with sunitinib (Sutent) vs sunitinib alone in patients with GIST. The first portion of part 1 of this trial enrolled patients who had received at least 1 prior line of therapy for GIST. The second evaluation of part 1 enrolled patients who had received at least 2 prior TKIs for GIST. Part 2 of this trial is enrolling patients who progressed on or are intolerant to imatinib.

Many patients with GIST receive imatinib (Gleevec) in the first line and may switch to local treatment options upon local progression, Somaiah says. Patients who progress with more diffuse disease may be eligible for enrollment in the Peak trial, Somaiah notes. GIST is a relatively easier-to-treat sarcoma because it has standard first-, second-, third-, and fourth-line therapeutic options, which patients may be referred to upon progression on imatinib, according to Somaiah. However, community oncologists should consider the Peak trial before prescribing standard lines of therapy beyond imatinib. Patients with GIST who receive treatment beyond imatinib are not eligible for enrollment in Peak and lose the chance to receive an additional line of targeted therapy, Somaiah emphasizes.

Data from part 1 of Peak, which were presented at the 2023 ASCO Annual Meeting, showed that bezuclastinib plus sunitinib was well tolerated, Somaiah notes. The safety profile of this combination supports further enrollment in this trial, Somaiah says.

Additionally, even patients in the Peak trial who are not randomly assigned to receive the investigative combination will receive sunitinib monotherapy in the control arm, Somaiah explains. This trial is distinct from placebo-controlled trials because it offers patients standard benefits in both arms, Somaiah emphasizes. Furthermore, patients who are randomly assigned to receive sunitinib monotherapy may have the option of crossing over to the investigative arm upon disease progression, Somaiah notes. Raising awareness about the advantages of this second-line trial can help more patients access a potentially beneficial treatment combination, Somaiah concludes.

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Neeta Somaiah, MD, discusses enrollment criteria for the phase 3 Peak trial in patients with gastrointestinal stromal tumor and the advantages of this trial’s design.

Dr Somaiah on the Peak Trial in GIST

Neeta Somaiah, MD, associate professor, Department of Sarcoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses ​remaining challenges in soft tissue sarcoma.

Due to the number of ​sarcoma subtypes, defining ​the optimal treatment for patients with soft tissue sarcoma remains an ongoing challenge, says Somaiah.

Additionally, other factors such as the degree of responsiveness and the likelihood of recurrence could also inform treatment selection​, Somaiah explains. Notably, many institutions have their own approach to adjuvant therapy.

In recent years, significant advances have been made in the advanced/metastatic setting; however, there is still room for improvement. Future research should include more subtype​-specific trials ​to better define which patient populations should receive targeted therapy, Somaiah concludes.

Neeta Somaiah, MD, discusses ​remaining challenges in soft tissue sarcoma.

 Dr. Somaiah on Remaining Challenges in Soft Tissue Sarcoma  

Neeta Somaiah, MD, assistant professor, Department of Sarcoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the next steps following the phase I findings of the CMB305 trial in patients with NY-ESO-1–positive recurrent soft tissue sarcoma. 

The initial next step is to determine the patient population who will benefit the most from this regimen, explains Somaiah. 

This drug can be compared against other regimens in the maintenance or third-line setting in order to determine if CMB305 will help a patient delay progression, states Somaiah. 

Neeta Somaiah, MD, assistant professor, Department of Sarcoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the next steps following the phase I findings of the CMB305 trial in patients with NY-ESO-1–positive recurrent soft tissue sarcoma.

Dr. Somaiah on Next Steps for CMB305 in Soft Tissue Sarcoma

Neeta Somaiah, MD, assistant professor, Department of Sarcoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the expression of NY-ESO-1 in patients with soft tissue sarcoma.

There were previous studies looking at the NY-ESO-1 expression across different sarcoma subtypes, explains Somaiah. However, the percentage of NY-ESO-1 expression in those other subtypes is around 30% whereas it is around 80% to 100% for soft tissue sarcoma.

Neeta Somaiah, MD, assistant professor, Department of Sarcoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the expression of NY-ESO-1 in patients with soft tissue sarcoma.


Dr. Somaiah on NY-ESO-1 Expression in Soft Tissue Sarcoma

Neeta Somaiah, MD, assistant professor, Department of Sarcoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses phase I findings of CMB305 in patients with NY-ESO-1—positive recurrent soft tissue sarcoma.

CMB305 is a prime boost immunotherapy that targets the NY-ESO-1 antigen, Somaiah explains. It consists of a dendritic cell targeting that is co-administered with G305, which is a potent agonist given with the entire NY-ESO-1 protein. This leads to robust immune response with both T cells and antibodies.

This is a phase I dose-escalation study with a dose-expansion cohort. Of the total 49 patients included in the safety population, 25 had sarcoma—the majority of which had synovial sarcoma or myxoid liposarcoma. The results of this study included patients who had relapsed metastatic sarcoma with a limited tumor burden.

It was found that the median overall survival (OS) of these 25 patients had not yet been reached. Eighty-three percent of patients were still alive at 1 year; the 12-month OS rate was 83%, and 76% of patients are still alive at 19 months.

Neeta Somaiah, MD, assistant professor, Department of Sarcoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses phase I findings of CMB305 in patients with NY-ESO-1–positive recurrent soft tissue sarcoma.

Neeta Somaiah, MD

Articles

Dr Somaiah on the Peak Trial in GIST

Dr. Somaiah on Remaining Challenges in Soft Tissue Sarcoma

Dr. Somaiah on Next Steps for CMB305 in Soft Tissue Sarcoma

Dr. Somaiah on NY-ESO-1 Expression in Soft Tissue Sarcoma

Dr. Somaiah on CMB305 in Soft Tissue Sarcoma