A Study to Investigate Efficacy & Safety of Intratumoral INT230-6 Compared to US Standard of Care in Adults With Soft Tissue Sarcomas (INVINCIBLE-3)

Summary

To compare Overall Survival (OS) for INT230-6 vs United States (US) Standard of Care (SOC) in participants with unresectable or metastatic liposarcoma, undifferentiated pleomorphic sarcoma or leiomyosarcoma who have disease progression prior to study enrollment following no more than 2 standard therapies, which must have included an anthracycline-based regimen, unless contraindicated, and then a maximum of 1 additional regimen.

Timeline

Start

2024-06-28

Primary completion

2027-12

Completion

2028-12

Publications

• Background Billingsley KG, Burt ME, Jara E, Ginsberg RJ, Woodruff JM, Leung DH, Brennan MF. Pulmonary metastases from soft tissue sarcoma: analysis of patterns of diseases and postmetastasis survival. Ann Surg. 1999 May;229(5):602-10; discussion 610-2. doi: 10.1097/00000658-199905000-00002.
• Background Beaver JA, Hazarika M, Mulkey F, Mushti S, Chen H, He K, Sridhara R, Goldberg KB, Chuk MK, Chi DC, Chang J, Barone A, Balasubramaniam S, Blumenthal GM, Keegan P, Pazdur R, Theoret MR. Patients with melanoma treated with an anti-PD-1 antibody beyond RECIST progression: a US Food and Drug Administration pooled analysis. Lancet Oncol. 2018 Feb;19(2):229-239. doi: 10.1016/S1470-2045(17)30846-X. Epub 2018 Jan 18.
• Background Bender LH, Abbate F, Walters IB. Intratumoral Administration of a Novel Cytotoxic Formulation with Strong Tissue Dispersive Properties Regresses Tumor Growth and Elicits Systemic Adaptive Immunity in In Vivo Models. Int J Mol Sci. 2020 Jun 24;21(12):4493. doi: 10.3390/ijms21124493.
• Background Bloom AC, Bender LH, Tiwary S, Pasquet L, Clark K, Jiang T, Xia Z, Morales-Kastresana A, Jones JC, Walters I, Terabe M, Berzofsky JA. Intratumorally delivered formulation, INT230-6, containing potent anticancer agents induces protective T cell immunity and memory. Oncoimmunology. 2019 Jul 16;8(10):e1625687. doi: 10.1080/2162402X.2019.1625687. eCollection 2019.
• Background Cassier PA, Polivka V, Judson I, Soria JC, Penel N, Marsoni S, Verweij J, Schellens JH, Morales-Barrera R, Schoffski P, Voest EE, Gomez-Roca C, Evans TR, Plummer R, Gallerani E, Kaye SB, Olmos D. Outcome of patients with sarcoma and other mesenchymal tumours participating in phase I trials: a subset analysis of a European Phase I database. Ann Oncol. 2014 Jun;25(6):1222-8. doi: 10.1093/annonc/mdu108. Epub 2014 Mar 7.
• Background Dasari S, Tchounwou PB. Cisplatin in cancer therapy: molecular mechanisms of action. Eur J Pharmacol. 2014 Oct 5;740:364-78. doi: 10.1016/j.ejphar.2014.07.025. Epub 2014 Jul 21.
• Background Demetri GD, von Mehren M, Jones RL, Hensley ML, Schuetze SM, Staddon A, Milhem M, Elias A, Ganjoo K, Tawbi H, Van Tine BA, Spira A, Dean A, Khokhar NZ, Park YC, Knoblauch RE, Parekh TV, Maki RG, Patel SR. Efficacy and Safety of Trabectedin or Dacarbazine for Metastatic Liposarcoma or Leiomyosarcoma After Failure of Conventional Chemotherapy: Results of a Phase III Randomized Multicenter Clinical Trial. J Clin Oncol. 2016 Mar 10;34(8):786-93. doi: 10.1200/JCO.2015.62.4734. Epub 2015 Sep 14.
• Background Gronchi A, Miah AB, Dei Tos AP, Abecassis N, Bajpai J, Bauer S, Biagini R, Bielack S, Blay JY, Bolle S, Bonvalot S, Boukovinas I, Bovee JVMG, Boye K, Brennan B, Brodowicz T, Buonadonna A, De Alava E, Del Muro XG, Dufresne A, Eriksson M, Fagioli F, Fedenko A, Ferraresi V, Ferrari A, Frezza AM, Gasperoni S, Gelderblom H, Gouin F, Grignani G, Haas R, Hassan AB, Hecker-Nolting S, Hindi N, Hohenberger P, Joensuu H, Jones RL, Jungels C, Jutte P, Kager L, Kasper B, Kawai A, Kopeckova K, Krakorova DA, Le Cesne A, Le Grange F, Legius E, Leithner A, Lopez-Pousa A, Martin-Broto J, Merimsky O, Messiou C, Mir O, Montemurro M, Morland B, Morosi C, Palmerini E, Pantaleo MA, Piana R, Piperno-Neumann S, Reichardt P, Rutkowski P, Safwat AA, Sangalli C, Sbaraglia M, Scheipl S, Schoffski P, Sleijfer S, Strauss D, Strauss S, Sundby Hall K, Trama A, Unk M, van de Sande MAJ, van der Graaf WTA, van Houdt WJ, Frebourg T, Casali PG, Stacchiotti S; ESMO Guidelines Committee, EURACAN and GENTURIS. Electronic address: [email protected]. Soft tissue and visceral sarcomas: ESMO-EURACAN-GENTURIS Clinical Practice Guidelines for diagnosis, treatment and follow-up☆. Ann Oncol. 2021 Nov;32(11):1348-1365. doi: 10.1016/j.annonc.2021.07.006. Epub 2021 Jul 22. No abstract available.
• Background Jones RL, Maki RG, Patel SR, Wang G, McGowan TA, Shalaby WS, Knoblauch RE, von Mehren M, Demetri GD. Safety and efficacy of trabectedin when administered in the inpatient versus outpatient setting: Clinical considerations for outpatient administration of trabectedin. Cancer. 2019 Dec 15;125(24):4435-4441. doi: 10.1002/cncr.32462. Epub 2019 Sep 10.
• Background Lammers T, Peschke P, Kuhnlein R, Subr V, Ulbrich K, Huber P, Hennink W, Storm G. Effect of intratumoral injection on the biodistribution and the therapeutic potential of HPMA copolymer-based drug delivery systems. Neoplasia. 2006 Oct;8(10):788-95. doi: 10.1593/neo.06436.
• Background Meyer M, Seetharam M. First-Line Therapy for Metastatic Soft Tissue Sarcoma. Curr Treat Options Oncol. 2019 Jan 24;20(1):6. doi: 10.1007/s11864-019-0606-9.
• Background von Mehren M, Kane JM, Agulnik M, Bui MM, Carr-Ascher J, Choy E, Connelly M, Dry S, Ganjoo KN, Gonzalez RJ, Holder A, Homsi J, Keedy V, Kelly CM, Kim E, Liebner D, McCarter M, McGarry SV, Mesko NW, Meyer C, Pappo AS, Parkes AM, Petersen IA, Pollack SM, Poppe M, Riedel RF, Schuetze S, Shabason J, Sicklick JK, Spraker MB, Zimel M, Hang LE, Sundar H, Bergman MA. Soft Tissue Sarcoma, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2022 Jul;20(7):815-833. doi: 10.6004/jnccn.2022.0035.
• Background Obeid M, Panaretakis T, Tesniere A, Joza N, Tufi R, Apetoh L, Ghiringhelli F, Zitvogel L, Kroemer G. Leveraging the immune system during chemotherapy: moving calreticulin to the cell surface converts apoptotic death from "silent" to immunogenic. Cancer Res. 2007 Sep 1;67(17):7941-4. doi: 10.1158/0008-5472.CAN-07-1622.
• Background Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982 Dec;5(6):649-55. No abstract available.
• Background Padhani AR, Ollivier L. The RECIST (Response Evaluation Criteria in Solid Tumors) criteria: implications for diagnostic radiologists. Br J Radiol. 2001 Nov;74(887):983-6. doi: 10.1259/bjr.74.887.740983. No abstract available.
• Background Phillips E, Jones RL, Huang P, Digklia A. Efficacy of Eribulin in Soft Tissue Sarcomas. Front Pharmacol. 2022 Mar 30;13:869754. doi: 10.3389/fphar.2022.869754. eCollection 2022.
• Background Stiller CA, Trama A, Serraino D, Rossi S, Navarro C, Chirlaque MD, Casali PG; RARECARE Working Group. Descriptive epidemiology of sarcomas in Europe: report from the RARECARE project. Eur J Cancer. 2013 Feb;49(3):684-95. doi: 10.1016/j.ejca.2012.09.011. Epub 2012 Oct 15.
• Background Rizvi NA, Hellmann MD, Brahmer JR, Juergens RA, Borghaei H, Gettinger S, Chow LQ, Gerber DE, Laurie SA, Goldman JW, Shepherd FA, Chen AC, Shen Y, Nathan FE, Harbison CT, Antonia S. Nivolumab in Combination With Platinum-Based Doublet Chemotherapy for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer. J Clin Oncol. 2016 Sep 1;34(25):2969-79. doi: 10.1200/JCO.2016.66.9861. Epub 2016 Jun 27.
• Background Sok M, Sentjurc M, Schara M, Stare J, Rott T. Cell membrane fluidity and prognosis of lung cancer. Ann Thorac Surg. 2002 May;73(5):1567-71. doi: 10.1016/s0003-4975(02)03458-6.
• Background Subbiah V, Hess KR, Khawaja MR, Wagner MJ, Tang C, Naing A, Fu S, Janku F, Piha-Paul S, Tsimberidou AM, Herzog CE, Ludwig JA, Patel S, Ravi V, Benjamin RS, Meric-Bernstam F, Hong DS. Evaluation of Novel Targeted Therapies in Aggressive Biology Sarcoma Patients after progression from US FDA approved Therapies. Sci Rep. 2016 Oct 17;6:35448. doi: 10.1038/srep35448.
• Background Wolchok JD, Hoos A, O'Day S, Weber JS, Hamid O, Lebbe C, Maio M, Binder M, Bohnsack O, Nichol G, Humphrey R, Hodi FS. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res. 2009 Dec 1;15(23):7412-20. doi: 10.1158/1078-0432.CCR-09-1624. Epub 2009 Nov 24.

Drugs

Indications