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Clinical Trial
. 2025 Jan 1;131(1):e35628.
doi: 10.1002/cncr.35628. Epub 2024 Nov 14.

Nivolumab and sunitinib in patients with advanced bone sarcomas: A multicenter, single-arm, phase 2 trial

Emanuela Palmerini  1 , Antonio Lopez Pousa  2 , Giovanni Grignani  3 , Andres Redondo  4 , Nadia Hindi  5   6   7 , Salvatore Provenzano  8 , Ana Sebio  2 , Jose Antonio Lopez Martin  9 , Claudia Valverde  10 , Javier Martinez Trufero  11 , Antonio Gutierrez  12 , Enrique de Alava  13   14 , Maria Pilar Aparisi Gomez  15   16 , Lorenzo D'Ambrosio  3   17 , Paola Collini  18 , Alberto Bazzocchi  19 , David S Moura  20 , Toni Ibrahim  1 , Silvia Stacchiotti  8 , Javier Martin Broto  5   6   7
Affiliations
Clinical Trial

Nivolumab and sunitinib in patients with advanced bone sarcomas: A multicenter, single-arm, phase 2 trial

Emanuela Palmerini et al. Cancer. .

Abstract

Background: Herein, we present the results of the phase 2 IMMUNOSARC study (NCT03277924), investigating sunitinib and nivolumab in adult patients with advanced bone sarcomas (BS).

Methods: Progressing patients with a diagnosis of BS were eligible. Treatment was comprised of sunitinib (37.5 mg/day on days 1-14, 25 mg/day afterword) plus nivolumab (3 mg/kg every 2 weeks). Primary end point was progression-free survival rate (PFSR) at 6 months based on central radiology review. Secondary end points were overall survival (OS), overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, and safety.

Results: A total of 46 patients were screened, 40 patients entered the study, and 38 underwent central radiological review and were evaluable for primary end point. Median age was 47 years (range, 21-74). Histologies include 17 (43%) osteosarcoma, 14 chondrosarcoma (35%, 10 conventional, four dedifferentiated [DDCS]), eight (20%) Ewing sarcoma, and one (2%) undifferentiated pleomorphic sarcoma. The PFSR at 6 months was 42% (95% confidence interval [CI], 27-58). With a median follow-up of 39.8 months (95% CI, 37.9-41.7), the median PFS and OS were 3.8 months (95% CI, 2.7-4.8) and 11.9 months (95% CI, 5.6-18.2). ORR by RECIST was 5%, with two of 38 partial responses (one of four DDCS and one of 17 osteosarcoma), 19 of 38 (50%) stable disease, and 17 of 38 (45%) progressions. Grade ≥3 adverse events were neutropenia (six of 40, 15%), anemia (5/40, hypertension (6/40, 15%), 12.5%), ALT/AST elevation (5/40, 12.5%), and pneumonitis (1/40, 2.5%). Seventeen percent of patients discontinued treatment due to toxicity, including a treatment-related grade 5 pneumonitis CONCLUSION: The trial met its primary end point in the BS cohort with >15% of patients progression-free at 6 months. However, the toxicity profile of this regimen was relevant.

Keywords: Ewing sarcoma; PD‐L1 inhibitor; anti‐angiogeninic; bone; dedifferentiated chondrosarcoma; immunotherapy; nivolumab; osteosarcoma; sarcoma; sunitinib.

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Conflict of interest statement

Emanuela Palmerini has served on advisory boards for Daiichi Sankyo, Deciphera Pharmaceuticals, Eusa Pharma, and SynOx Therapeutics. Giovanni Grignani reports grants and personal fees from PharmaMar, grants from Novartis, and personal consulting fees from Lilly, Pfizer, Bayer, and Eisai. Andres Redondo reports grants and personal fees from PharmaMar; personal fees from Lilly, Novartis, Amgen, AstraZeneca, and Tesaro; grants and personal fees from Roche; and grants from Eisai. Nadia Hindi reports grants, personal fees, and nonfinancial support from PharmaMar; personal fees from Lilly; grants from Eisai and Novartis; and research funding for clinical studies (institutional) from PharmaMar, Eli Lilly, AROG, Bayer, Eisai, Lixte, Karyopharm, Deciphera, GlaxoSmithKline, Novartis, Blueprint, Nektar, Forma, Amgen, and Daiichi Sankyo. Salvatore Provenzano reports personal fees for consultancy from Italfarmaco and Boehringer Ingelheim; and the spouse employed in AstraZeneca. Silvia Stacchiotti reports personal financial interests including honoraria, consultancy, or advisory role from Agentus, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Deciphera, Ikena, Gentili, GlaxoSmithKline, Ipsen, Nec Oncolimmunity, Novartis, Pharmamar, Pharma Essentia, Regeneron Springworks, and Servier; and institutional financial interests from Abbisko, Adaptimmune, Advenchen, Bayer, Blueprint, Boehringer Ingelheim, Daiichi Sankyo, Deciphera, EISAI, Epizyme, Foghorn, Hutchinson, Inhbrix, Karyopharm, Novartis, Pharmamar, RainThera, and Springworks. Jose Antonio Lopez Martin reports honoraria for advisory board participation and travel support from PharmaMar, Eli Lilly, Bayer, Eisai, Novartis, Bristol‐Myers Squibb, MSD, Roche, Celgene, Pierre Fabre, Pfizer, GlaxoSmithKline, Daiichi Sankyo, Amgen, and Chobani. Javier Martinez Trufero reports honoraria for advisory board participation and travel support from PharmaMar, Eli Lilly, Eisai, Merck Sharp & Dohm, Merck, GlaxoSmithKline, and Roche. Lorenzo D’Ambrosio reports advisory board participation for Boehringer Ingelheim, AstraZeneca, PSI CRO Italy, and GlaxoSmithKline; and travel support from PharmaMar, GlaxoSmithKline, and AstraZeneca. Enrique de Alava reports personal fees and nonfinancial support from Roche, Bristol‐Myers Squibb, and PharmaMar; and personal fees from Bayer. David S. Moura reports institutional research grants from PharmaMar, Eisai, Immix BioPharma, and Novartis outside the submitted work; travel support from PharmaMar, Eisai, Celgene, Bayer, and Pfizer, and personal fees from Tecnopharma. Javier Martin Broto reports research grants from PharmaMar, Eisai, Immix BioPharma, and Novartis; honoraria for advisory board participation and expert testimony from PharmaMar, Eli Lilly, Bayer, and Eisai; and research funding for clinical studies (institutional) from PharmaMar, Eli Lilly, AROG, Bayer, Eisai, Lixte, Karyopharm, Deciphera, GlaxoSmithKline, Novartis, Blueprint, Nektar, Forma, Amgen, and Daiichi Sankyo. The other authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
CONSORT diagram. CONSORT, Consolidated Standards of Reporting Trials; ECOG, Eastern Cooperative Oncology Group; RECIST, Response Evaluation Criteria in Solid Tumors.
FIGURE 2
FIGURE 2
Progression‐free survival in 38 patients with relapsed bone sarcomas undergoing sunitinib and nivolumab.
FIGURE 3
FIGURE 3
Overall survival in 40 patients with relapsed bone sarcomas undergoing sunitinib and nivolumab.
FIGURE 4
FIGURE 4
Response to treatment by patient according to RECIST 1.1. All evaluable patients (n = 40) are shown. Tumor diameter was measured in millimeters. The dashed lines represent 20% increase in diameter and 30% decrease in diameter (RECIST progression and response cutoffs, respectively). *No size variation. RECIST, Response Evaluation Criteria in Solid Tumors.
FIGURE 5
FIGURE 5
Progression‐free survival rate to treatment by patient based on RECIST central radiological assessment. Each patient in the efficacy population is represented as bars (n = 40). The vertical dashed line represents the median progression‐free survival. The stars represent patients achieving RECIST objective responses. The arrows represent patients nonprogressing in the last central radiological assessment. RECIST, Response Evaluation Criteria in Solid Tumors.
See this image and copyright information in PMC

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