Experts Share Intriguing Early-Phase Sarcoma Studies From the 2024 ESMO Congress

John Andrew Livingston, MD, MS

In case you missed the variety of sarcoma sessions at the 2024 ESMO Congress or want to know more about up-and-coming research in the field, key experts in sarcoma have highlighted several studies and emerging therapies to keep an eye on. Read on to see their thoughts and insights.

A Phase 1 Trial of Palbociclib Plus Retifanlimab in Advanced Dedifferentiated Liposarcoma

“One of the studies presented in the sarcoma sessions at the 2024 ESMO Congress evaluated the combination of a CDK4/6 inhibitor and anti–PD-1 therapy in patients with dedifferentiated liposarcoma,” John Andrew Livingston, MD, MS, said in an interview with OncLive^®. “This has been a question of interest for our field. We have data with each [drug] as a single-agent in dedifferentiated liposarcoma, and [in this single-arm phase 2 trial (NCT04438824)], investigators studied the combination [in patients with this disease].”

Livingston is an associate professor in the Department of Sarcoma Medical Oncology in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston.

In this phase 2 trial, palbociclib (Ibrance) plus retifanlimab-dlwr (Zynyz) elicited a confirmed objective response rate (ORR) of 14.3% (95% CI, 4.7%-33.6%) and a disease control rate of 50% (95% CI, 32.6%-67.4%) among 28 patients with unresectable or metastatic dedifferentiated liposarcoma who had received any number of prior lines of therapy.¹ The median duration of response (DOR) was not reached (NR; 95% CI, 9.4-NR). Furthermore, the median progression-free survival (PFS) was 2.2 months (95% CI, 1.8-NR), and the median overall survival (OS) was 24.8 months (95% CI, 24.8-NR).

“We saw some nice efficacy signals, so that warrants follow-up,” Livingston emphasized. “This is a theme that’s being built out further. There’s an ongoing randomized [phase 2] study [NCT05694871] in the United States that’s investigating either palbociclib [monotherapy] or palbociclib plus the immunotherapy cemiplimab[-rwlc (Libtayo)], which will help us better [elucidate the benefit of] adding immunotherapy or immune checkpoint blockade to CDK4/6 inhibitors in dedifferentiated liposarcoma.”

The EREMISS Trial

“One study of interest was the [phase 2] EREMISS trial [NCT03793361],” said Elise F. Nassif Haddad, MD, PhD, who is an assistant professor in the Department of Sarcoma Medical Oncology in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center. “It investigated regorafenib [Stivarga] maintenance after initial first-line treatment with doxorubicin-based chemotherapy [in patients with non-adipocytic soft tissue sarcomas]. Usually, patients then go on a therapeutic break until progression.”

In EREMISS, patients who had achieved stable disease (SD) or partial response (PR) with 6 cycles of doxorubicin-based chemotherapy were randomly assigned to receive regorafenib (n = 65) or placebo (n = 62).² Best responses in the regorafenib arm were PR (8.1%), SD (40.3%), and progressive disease (PD; 51.6%). Best responses in the placebo arm were complete response (1.7%), PR (10.0%), SD (68.3%), and PD (20.0%). The median PFS per blinded central review was 5.6 months (95% CI, 3.9-8.2) with regorafenib vs 3.5 months (95% CI, 1.8-3.6) with placebo (adjusted HR, 0.53; 95% CI, 0.36-0.78; P = .001). The median OS was 27.6 months (95% CI, 19.9-33.0) with regorafenib vs 20.5 months (15.8-25.1) with placebo (adjusted HR, 0.78; 95% CI, 0.50-1.22; P = .28).

“Although the OS data were not statistically significant in that trial, [this treatment approach reflects] a new concept of maintenance therapy that we haven’t been using in sarcoma up to now,” Haddad noted. “However, it’s extremely important [to note that the trial showed] a trend for better OS and a significant benefit in PFS. [These data support the findings from] another [phase 3] French trial, LMS04 [NCT02997358], which was published in The New England Journal of Medicine [on September 4, 2024]. The [study] showed in leiomyosarcoma that trabectedin [Yondelis] maintenance also prolongs OS. Both these trials have shown that potentially using maintenance after an induction with doxorubicin-based chemotherapy will prolong survival for patients.”

Botensilimab Plus Balstilimab in Relapsed/Refractory Metastatic Sarcoma

“I enjoyed the mini oral presentations, not only because I was involved in the [phase 1/2 IMMUNOSARC II (NCT03277924)] presentation of nivolumab [Opdivo] plus sunitinib [Sutent] in patients with clear cell sarcoma, but because there were other presentations [that were] appealing,” Javier Martín-Broto, MD, PhD, a sarcoma medical oncologist at the University Hospital Fundacion Jimenez Diaz in Madrid, Spain, said to OncLive. “For instance, the double effect against CTLA-4 and PD-1 in [a phase 1 trial (NCT03860272)] in the angiosarcoma subset [was interesting]. The ORR, and most importantly the DOR, were striking observations. The combination is clearly promising in this regard.”

In this single-arm phase 1 trial, the combination of botensilimab (AGEN1181) and balstilimab (AGEN2034) produced responses across a broad range of sarcomas. Among efficacy evaluable patients in the overall population (n = 52), the ORR was 23% (95% CI, 13%-37%), and the median DOR was 21.7 months (95% CI, 3.4-NR).³ Among patients with cutaneous or visceral adenosarcoma (n = 18), the ORR was 39% (95% CI, 17%-64%), and the median DOR was 21.7 months (95% CI, 1.9-NR).

“Some other combinations in gastrointestinal stromal tumor [GIST] and in SDH-deficient GIST [incorporating] new compounds previously used in chronic myeloid leukemia also deserve to be published and known. In some rare, niche sarcomas, there were substantial contributions this year at the ESMO Congress,” Martín-Broto concluded.

References

1. Rosenbaum E, Qin L-X, Dickson M, et al. A phase II study of palbociclib combined with the PD-1 inhibitor retifanlimab in patients with advanced dedifferentiated liposarcoma. Ann Oncol. 2024;35(suppl_2):S1031-S1061. doi:10.1016/annonc/annonc1610
2. Penel N, Italiano A, Wallet J, et al. EREMISS trial: A double-blind placebo (PBO)-controlled randomised trial assessing efficacy/safety of regorafenib (REGO) as maintenance therapy after 1st line doxorubicin-based chemotherapy in advanced soft-tissue sarcoma (ASTS) patients (pts). Ann Oncol. 2024;35(suppl_2):S1031-S1061. doi:10.1016/annonc/annonc1610
3. Wilky BA, Trent JC, Tsimberidou AM, et al. Updated efficacy and safety of botensilimab plus balstilimab in patients with refractory metastatic sarcoma from an expanded phase I study. Ann Oncol. 2024;35(suppl_2):S1031-S1061. doi:10.1016/annonc/annonc1610