Lartruvo (olaratumab)

P1, N=50, Recruiting, Telix Pharmaceuticals (Innovations) Pty Ltd | Not yet recruiting --> Recruiting | Initiation date: Aug 2024 --> Oct 2024 | Trial primary completion date: Dec 2025 --> Mar 2026

P1, N=41, Completed, Eli Lilly and Company | Phase classification: P1a/1b --> P1

P3, N=509, Completed, Eli Lilly and Company | Active, not recruiting --> Completed

P1, N=50, Not yet recruiting, Telix Pharmaceuticals (Innovations) Pty Ltd

P3, N=509, Active, not recruiting, Eli Lilly and Company | Trial completion date: Dec 2024 --> Jul 2024

Antitumor activity was observed in some patients in DEC, combination was well tolerated with manageable safety profile. Further studies are warranted to evaluate efficacy/mechanistic impact of platelet-derived growth factor receptors inhibitor with immune checkpoint modulator coadministration.

The most common 1L treatment was doxorubicin (doxo) with olaratumab (23.5%), followed by gemcitabine and cisplatin (15.7%)...In 2L, eribulin was the most common (21.9%), followed by gemcitabine (15.6%)... Patient demographics are consistent with a 2012 report on 208 patients from 11 institutions (10 European members of the Connective Tissue Cancers Network of Excellence and Memorial Sloan Kettering Cancer Center [New York, NY]); however, median OS observed is lower than the reported 15.2 months. For those receiving 1L doxo monotherapy or in combination, rwPFS was comparable to this report and to a 2017 report on 51 patients at MD Anderson Cancer Center (Houston, TX). These results may highlight an awareness gap between academic centers and community practices for treating DDLPS.

We present the case of a 73-year-old woman with a mismatch repair deficient (MMRd) undifferentiated cardiac sarcoma, who achieved a complete and durable response with the anti-PD1 inhibitor pembrolizumab after the failure of standard treatment consisting of doxorubicin together with olaratumab. The genomic analysis of the cardiac UDS displayed several markers known to predict response to ICIs: the tumor harbored a high TMB (> 10 mutations/Mb) and a MMRd/MSI signature. Of note, inactivating mutations of both FAT1 and NOTCH2 have also been associated with ICI therapy response in epithelial tumors. Moreover, the tumor displayed an extensive infiltrate by CD8+ T cells, and PD-L1 was expressed in the tumor immune microenvironment.

In the first-line setting, the results of this trial were pivotal for numerous reasons; Doxorubicin-Trabectedin is the first combination that has been proven to be more effective in terms of PFS, ORR and trend of OS compared with doxorubicin alone; moreover, it is clear that trials regarding soft tissue sarcoma should strive to be histology-driven.

Its combination with doxorubicin showed encouraging results in a phase II trial, leading to its approval...Previous premedication with dexamethasone and H1 antagonist was administered... Trabectedin plus olaratumab was a safe regimen, allowing full doses of both drugs in combination. Its toxicity and efficacy profiles seem favorable in this limited prospective series. Translational analyses are ongoing.

Our experience from a tertiary care center shows results similar to those reported in the literature. The immunogenicity and heterogeneity of soft tissue sarcomas pose a challenge to the treatment of soft tissue sarcomas, but they also allow a wide array of possible management solutions.

The expression of PDGF ligands and receptors varies across sarcoma histological subtypes. PDGFA and D expression levels independently and inversely correlate with the risk of metastatic relapse.

Patients received olaratumab monotherapy at 15 mg/kg (Part A) or 20 mg/kg (Part B) on Days 1 and 8 of the first 21-day cycle, followed by olaratumab combined with standard fixed doses of chemotherapy with doxorubicin, vincristine/irinotecan, or high-dose ifosfamide by investigator choice for subsequent 21-day cycles. There was one complete response (rhabdomyosarcoma [Part B vincristine/irinotecan arm]) and three partial responses (two rhabdomyosarcoma [Part A doxorubicin arm and Part C doxorubicin arm]; one pineoblastoma [Part B vincristine/irinotecan arm]). Olaratumab was tolerable and safely administered in combination with chemotherapy regimens commonly used in children and adolescents.

Case 1 had PDL-1 + immune cells for which pembrolizumab was started...Doxorubicin and olaratumab were started for palliation. PCSs are challenging to diagnose due to their variable clinical presentations... PCSs are challenging to diagnose due to their variable clinical presentations. Multimodal imaging increases suspicion for malignancy. Treatment is surgical resection when possible.