A phase 2 study using ipilimumab, nivolumab, and trabectedin for previously untreated metastatic soft tissue sarcoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11562-11562
Author(s):  
Erlinda Maria Gordon ◽  
Victoria S. Chua ◽  
Ted T. Kim ◽  
Neal Shiv Chawla ◽  
Don Arlen Brigham ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Phase 2 ◽  
First Line ◽  
Phase 2 Study ◽  
Common Grade ◽  
Metastatic Soft Tissue Sarcoma

11562 Background: Sarcoma cells are most immunogenic earlier in the disease course and before treatment when the immune system can recognize and destroy them. Hypothesis: Immune checkpoint inhibitors would be most effective when given to previously untreated patients with metastatic soft tissue sarcoma. Methods: Eligible patients for this Phase 2 study are previously untreated patients ≥ 18 years of age with unresectable or metastatic soft tissue sarcoma, with measurable disease by RECIST v1.1. Immune checkpoint inhibitors Ipilimumab (I) and Nivolumab (N) were given with Trabectedin (T), a marine derived alkaloid with defined doses of I (1 mg/kg i.v. q 12 weeks), N (3 mg/kg i.v. q 2 weeks), and T (1.2 mg/m2 i.v. q 3 weeks). Primary endpoints: (1) Objective response rate by RECIST v1.1 via CT scan or MRI, (2) Progression-free survival (PFS): from first day of treatment to disease progression or death due to any cause; otherwise, it is censored at the time of last follow-up, and (3) Overall survival: from first day of treatment to death due to any cause; otherwise, it is censored at the time of last follow-up. Results: There were eighty-two evaluable subjects, having completed the first cycle of I, N, and T and have had a CT or MRI scan at the 6-week follow-up period. Best Overall Response by RECIST v1.1 = 7 CR (2 surgical CR), 9 PR, 54 SD, and 12 PD. Disease control rate was 85.4%. The median PFS was >6.4 (range: 0-32) months; 6-month PFS rate: 57.3%. The median OS was >12.0 (0-38) months; 6-month OS rate: 78.8%. Safety analysis: The most common Grade 3 TRAEs include increased ALT (26), anemia (11), increased AST (9), and fatigue (8). Common Grade 4 TRAEs include thrombocytopenia (2), increased AST (2), increased ALT (2), and increased CPK (2). There was one Grade 5 TRAE of rhabdomyolysis (1). Conclusions: Taken together, these results suggest that first-line combinatorial therapy with I, N, and T are (1) synergistic, and (2) may be equal or superior to, and safer than, standard first line therapy for advanced/metastatic soft tissue sarcoma. Clinical trial information: NCT03138161.

SAINT: Results of an expanded phase II study using safe amounts of ipilimumab (I), nivolumab (N), and trabectedin (T) as first-line treatment of advanced soft tissue sarcoma [NCT03138161].

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 11520-11520
Author(s):  
Erlinda Maria Gordon ◽  
Victoria S. Chua-Alcala ◽  
Katherine Kim ◽  
Paul Stendahl Dy ◽  
Micaela Kristina Paz ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Disease Control ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Synergistic Activity ◽  
First Line

11520 Background: Sarcoma cells are most immunogenic earlier in the disease. Hypothesis: Immune checkpoint inhibitors would be most effective when given as first-line therapy. Methods: Eligible patients include previously untreated male or female patients, ≥ 18 years of age with locally advanced unresectable or metastatic soft tissue sarcoma (STS), with measurable disease by RECIST v1.1. Immune checkpoint inhibitors I (1 mg/kg i.v. q 12 weeks) and N (3 mg/kg i.v. q 2 weeks) were given with T (1.2 mg/m2 i.v. q 3 weeks), a tumoricidal agent that depletes growth-promoting macrophages in the tumor microenvironment. Primary endpoint: Objective response rate by RECIST v1.1; Secondary endpoints: (1) Progression-free survival (PFS) at 6 months, (2) Overall survival (OS) at 6, 9, 12, 24, and 48 months, and (3) Incidence of adverse events. Results: Efficacy analysis: There were forty-one evaluable subjects. Best overall response rate was 19.5%; disease control rate 87.8%. The median OS was >12.5 months; median PFS was >6.0 months (6-month OS rate: 75%; 6-month PFS rate: 50%). Safety analysis: Grade 3 TRAEs include fatigue (n = 5), increased TSH (n = 3), decreased TSH (n = 1), adrenal insufficiency (n = 1), hyperglycemia (n = 1), dehydration (n = 1), hyponatremia (n = 2), bipedal edema (n = 2), increased AST (n = 8), increased ALT (n = 19), increased ALP (n = 2), increased CPK (n = 3), port site infection (n = 2), psoriasis exacerbation (n = 1), anemia (n = 6), thrombocytopenia (n = 2), and neutropenia (n = 2). Grade 4 TRAES include neutropenia (n = 1), thrombocytopenia (n = 2), and increased CPK (n = 2). Conclusions: These data suggest that combinatorial therapy with Ipilimumab, Nivolumab and Trabectedin (1) may have synergistic activity in achieving disease control, and (2) is safe with manageable toxicity for patients with previously untreated STS. Clinical trial information: NCT03138161 . [Table: see text]

scholarly journals Phase 2 study of eribulin in patients with previously treated advanced or metastatic soft tissue sarcoma†

2016 ◽  
Vol 47 (2) ◽  
pp. 137-144 ◽  
Author(s):  
Akira Kawai ◽  
Nobuhito Araki ◽  
Yoichi Naito ◽  
Toshifumi Ozaki ◽  
Hideshi Sugiura ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Phase 2 ◽  
Phase 2 Study ◽  
Metastatic Soft Tissue Sarcoma ◽  
Previously Treated

Tislelizumab in combination with chemotherapy in Chinese patients with advanced gastric or gastroesophageal junction (G/GEJ) cancer: Results from one cohort of an ongoing phase 2 study.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 11-11
Author(s):  
Yu-Xian Bai ◽  
En Xiao Li ◽  
Buhai Wang ◽  
Xianglin Yuan ◽  
Nong Xu ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Gastroesophageal Junction ◽  
Chinese Patients ◽  
Phase 2 ◽  
First Line ◽  
Cancer Data ◽  
Cell Clearance ◽  
Phase 2 Study ◽  
Target Disease

11 Background: Tislelizumab, a humanized IgG4 mAb with high affinity and specificity for PD-1, was specifically engineered to minimize FcγR binding on macrophages, thus abrogating antibody-dependent phagocytosis, a potential mechanism of T-cell clearance and resistance to anti-PD-1 therapy. This phase 2 study (NCT03469557) evaluated safety, tolerability, and antitumor activity of first-line tislelizumab plus chemotherapy in Chinese pts with advanced G/GEJ or esophageal cancer; data from the G/GEJ cohort are presented here. Methods: Adult pts with histologically or cytologically confirmed HER2 negative G/GEJ were treated with tislelizumab (200 mg IV Q3W) + oxaliplatin (130 mg/m² IV Q3W for up to 6 cycles) + capecitabine (1000 mg/m² BID, Days 1–14 Q3W). AEs were assessed per CTCAE v4.03; tumor responses were assessed every 9 wks. Results: As of 13 June 2018, 15 G/GEJ pts (median age, 59 yr; M/F, 11/4) were enrolled; median treatment duration was 171 days (range 21-251). AEs in > 2 pts considered related to chemotherapy and/or tislelizumab are detailed in the Table. No fatal AEs occurred. Three pts discontinued treatment due to ascites or increased ALT, AST, or total bilirubin. With a median follow up of 181 days, 46.7% (n = 7) had confirmed PR, 20% (n = 3) had SD, 13.3% (n = 2) with non-target disease only at baseline had non-CR/non-PD, 6.7% (n = 1) had PD, and 13.3% (n = 2) did not have evaluable disease. ORR and DCR were 46.7% (n = 7/15) and 80% (n = 12/15), respectively. Conclusions: First-line tislelizumab plus chemotherapy was generally well tolerated and antitumor activity was observed in pts with advanced G/GEJ cancer. Clinical trial information: NCT03469557. [Table: see text]

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