GALLANT: A phase 2 study using metronomic gemcitabine, doxorubicin, nivolumab, and docetaxel as second/third-line therapy for advanced sarcoma (NCT04535713).

Authors

null

Noufil Adnan

Sarcoma Oncology Center, Santa Monica, CA

Noufil Adnan , Simranjit Sekhon , Sant P. Chawla , Ted T. Kim , Victoria S. Chua-Alcala , Mitchel Fernando , Amir Ahari , William Feske , Doris V. Quon , Erlinda Maria Gordon

Organizations

Sarcoma Oncology Center, Santa Monica, CA, Cancer Center Of Southern California, Santa Monica, CA, Sarcoma Oncology Research Center, Santa Monica, CA, Sarcoma Oncology Center, Tracy, CA, Medical Imaging Center of Southern California, Santa Monica, CA

Research Funding

No funding received

Background: In our experience, combinatorial therapy with lower doses of doxorubicin, gemcitabine, and docetaxel has been effective with a manageable toxicity profile in patients with advanced soft tissue sarcomas. Hypothesis: The addition of nivolumab will have synergistic effects and improve treatment outcomes. Methods: Primary objective: To assess progression-free survival; Secondary objectives: (1) To evaluate best overall response during treatment period confirmed in a 6-week follow-up, (2) PFS rate at 6 and 9 months, (3) Overall survival rate at 6, 12 months, and (4) Incidence of treatment-related adverse events (TRAEs). Inclusion criteria: Previously treated male and female subjects, > 18 years of age, pathologically confirmed diagnosis of locally advanced, unresectable, or metastatic sarcoma, measurable disease by RECIST v1.1, and acceptable hematologic and organ functions. Exclusion Criteria: History of autoimmune disorder. Treatment schedule: Metronomic doses of gemcitabine (600 mg/m2 max:1000 mg), doxorubicin (18 mg/m2; max: 32 mg), docetaxel (25 mg/m2; max:42 mg) on Day 1 and Day 8, and nivolumab (240 mg) on Day 1 only. Repeat treatment cycles may be given every three weeks if toxicity grade is <1. Results: This is an Interim Report on the modified Intent-to-treat population (n = 43). This population completed at least one treatment cycle and had a follow-up CT or MRI scan at week 6. The most common histological subtypes in this group include leiomyosarcoma (n = 15), pleomorphic sarcoma (n = 4), synovial sarcoma (n = 4), liposarcoma (n = 3), osteosarcoma (n = 3) and other (n = 10). Best Overall Response = 2 CR (surgical CR), 6 PR, 30 SD, 5 PD. The disease control rate (CR+PR+SD) was 88.4%. Median PFS was > 4.6 (range: 1-27) months; 4 month PFS rate 60%. Median OS 6.2 months, with 4-month OS 74%. Historically, the median PFS on preceding lines of therapy was 2 (range: 1-14) months. There were no unexpected side effects noted in this study. The most common grade 3/4 TRAEs include Fatigue (n = 13), Nausea (n = 9), Neutropenia (n = 8), thrombocytopenia (n = 6), Anemia (n = 6). Conclusions: The GALLANT protocol using metronomic Gemcitabine, Doxorubicin (Adriamycin), Nivolumab, and Docetaxel (Taxotere) (1) is an effective regimen as second/third-line therapy for advanced sarcoma with no unexpected side effects, and (2) may have synergistic activity when this metronomic chemotherapy is combined with an immune checkpoint inhibitor. Clinical trial information: NCT04535713.

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Abstract Details

Meeting

2022 ASCO Annual Meeting

Session Type

Poster Discussion Session

Session Title

Sarcoma

Track

Sarcoma

Sub Track

Soft Tissue Tumors

Clinical Trial Registration Number

NCT04535713

Citation

J Clin Oncol 40, 2022 (suppl 16; abstr 11518)

DOI

10.1200/JCO.2022.40.16_suppl.11518

Abstract #

11518

Poster Bd #

423

Abstract Disclosures