1725MO - IMMUNOSARC II master trial (phase II of sunitinib and nivolumab): Results from the clear cell sarcoma (CCS) cohort: A GEIS, ISG, and UCL study

Background

CCS is an ultra-rare sarcoma driven by a specific translocation, more often EWSR1-ATF1, for which chemotherapy offers limited activity (mPFS 3 months) in retrospective series. MET inhibitors were prospectively explored, obtaining an ORR of 3.8%, mPFS of 4.4 months, 6-month PFS rate of 27%, and mOS of 9.2 months in 28 treated patients with crizotinib, and an ORR of 9%, and mPFS of 2 months in 11 patients treated with tivantinib. A specific CCS cohort was chosen in this trial based on signals of activity detected in IMMUNOSARC-I (phase I/II trial testing nivolumab and sunitinib (NiSu) in sarcomas) trial.

Methods

Patients aged 12-80 y, with advanced, progressive, and measurable CCS were enrolled after central pathology confirmation. Sunitinib was administered at 37.5 mg/d during the first 2 weeks, from then on at 25 mg/d along with nivolumab 240 mg every 2 weeks. Prior antiangiogenics but not anti-PD1/PDL1 were allowed. The primary endpoint was 6-month PFS rate, and it was considered H0/H1 as 25/55%. With Simon 2-stage Minimax design, error I 0.05 and power 0.90, at least 10 out of 23 patients should be free of progression at 6 months. For each case, a molecular confirmation demonstrating at least EWSR1 rearrangement was required.

Results

At the time of analysis, 20 patients were evaluable for the primary endpoint, 28% were still under treatment, 63% ended the treatment due to progression, and 9% due to toxicity. With a median follow-up of 12.6 months (95% CI 1.10-24.10), the 6-month PFS rate was 50% (95% CI 26-75) while the mPFS was 7.83 months (95% 1.28-14.39). From 18 patients who underwent at least one radiological assessment, 3 obtained PR (17%), 11 SD (61%), and 4 PD (22%). The median of OS was 17 months (95% CI 8-26). The ancillary molecular investigations concluded that all cases had EWSR1 rearrangement, 6 were confirmed by NGS, 12 by FISH and 2 by PCR. Main all-grade drug-related toxicities were lymphocytopenia: 28.6%, anemia: 23.8%, leukopenia: 19.0% and diarrhea: 23.8%. There were 1 G4 (hypercalcemia) and 15 G3 (being anemia 14.3% and lymphopenia 9.5% the most common).

Conclusions

While further studies are needed, initial findings suggest NiSu could be a valuable addition to the current armamentarium for CCS management.

Clinical trial identification

NCT03277924.

Editorial acknowledgement

Legal entity responsible for the study

GEIS (Spanish Group for Research on Sarcoma) Grupo Español De Investigacion En Sarcomas (GEIS).

Funding

Bristol Mayer Squibb; Pfizer.

Disclosure

J. Martin-Broto: Financial Interests, Personal, Advisory Board, Honoraria: Lilly, PharmaMar, Eisai, Bayer, Roche, Boehringer Ingelheim, Amgen; Financial Interests, Personal, Invited Speaker: PharmaMar; Financial Interests, Personal, Advisory Board, Speaker: Tecnofarma, Asofarma; Financial Interests, Personal, Other, Profits: Sarcoma Research Solutions SL; Financial Interests, Institutional, Coordinating PI: PharmaMar, Eisai, Novartis, IMMIX Biopharma, Lixte, Karyopharm, Bayer, Celgene, Pfizer, BMS, Lilly; Financial Interests, Institutional, Local PI: Blueprint, Deciphera, NEKTAR, FORMA, Amgen, Daiichi Sankyo, AROG, Adaptimmune, GSK, Ran Therapeutics, INHIBRX, Ayala Pharmaceuticals, Philogen, Cebiotex, PTC Therapeutics, Inc. and SpringWorks therapeutics. E. Palmerini: Financial Interests, Personal, Advisory Board: SynOx, Daiichi Sankyo, Deciphera Pharmaceuticals; Financial Interests, Personal, Invited Speaker: Peer View Educational. C.M. Valverde Morales: Financial Interests, Personal, Advisory Board: PharmaMar, Bayer, GSK, Mundipharma, Lilly, Boehringer Ingelheim, Deciphera, NEC OncoImmunity AS; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Institutional, Local PI, Clinical Trial: Adaptimmune, Karyopharm, Lilly, Foghorn Therapeutics, Ayala therapeutics, Inhibrx, Philogen, Intensity Therapeutics; Financial Interests, Institutional, Coordinating PI, Clinical Proyect: Bayer; Financial Interests, Institutional, Local PI, Clinical Trial, clinical project: Boheringer; Financial Interests, Institutional, Local PI, Clincial Trial: PharmaMar, PTC Therapeutics; Financial Interests, Institutional, Coordinating PI, Clincial Trial: Peptomyc S.L; Non-Financial Interests, Member of Board of Directors, President 2018-ongoing: GEIS- Spanish Sarcoma Group for Research. A. Sebio Garcia: Financial Interests, Personal, Advisory Board: Boehringer Ingelhaim, PharmaMar, Deciphera; Financial Interests, Personal, Other, Travel expenses: Cebiotex, Merck; Non-Financial Interests, Member of Board of Directors: Spanish Sarcoma Group. A. Redondo: Financial Interests, Personal, Invited Speaker: MSD, AstraZeneca, GSK, PharmaMar, Pharma&; Financial Interests, Personal, Advisory Board: MSD, AstraZeneca, GSK, PharmaMar, Boehringer Ingelheim; Financial Interests, Institutional, Local PI: Roche, Eisai, PharmaMar. S. Stacchiotti: Financial Interests, Personal, Advisory Board: Bayer, Daiichi Sankyo, Ikena, Regeneron, NEC Oncoimmunity AS, Pharma Essentia; Financial Interests, Personal, Other, Travel Coverage to scientific conference: PharmaMar; Financial Interests, Personal, Advisory Board, Advisory board meeting: Agenus; Financial Interests, Personal, Advisory Board, Advisory board meetings: Boehringer; Financial Interests, Personal, Invited Speaker, Lectures: Gentili; Financial Interests, Personal, Advisory Board, Advisory board: Servier; Financial Interests, Institutional, Local PI: Advenchen, Deciphera, Epizyme, Daiichi Sankyo, GSK, Karyopharm, PharmaMar, SpringWorks, Hutchison MediPharma International Inc, Inhibrix, Inhbrix; Financial Interests, Institutional, Coordinating PI: Bayer; Financial Interests, Institutional, Funding: Blueprint, Novartis; Financial Interests, Institutional, Other, Co-investigator in clinical study: Boehringer; Non-Financial Interests, Member of Board of Directors, Secretary: Connective Tissue Oncology Society; Non-Financial Interests, Advisory Role: Chordoma Foundation, Epithelioid Haemangiondothelioma Foundation, Desmoid Foundation, Epithelioid Hemangioendothelioma (EHE) Rare Cancer Charity (UK); Non-Financial Interests, Other, Secretary: EORTC soft tissue and bone sarcoma group; Non-Financial Interests, Leadership Role, President: Italian Sarcoma Group. S. Strauss: Financial Interests, Personal, Advisory Board: GSK, Inhibrx; Financial Interests, Personal, Advisory Board, medical advisor: Ceridwen Oncology; Financial Interests, Personal, Invited Speaker, speaker at education day: Boehringer Ingelheim. G. Grignani: Financial Interests, Personal, Invited Speaker, Talk: PharmaMar; Financial Interests, Personal, Advisory Board: Lilly, Eisai, Merck, Bayer, GSK, Boehringer Ingelheim, Incyte, deciphera; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Institutional, Other, Grant: PharmaMar, Bayer, Novartis. S. Aliberti: Financial Interests, Personal, Writing Engagement, Role To Write Scientific Works: Eisai, Gentili; Non-Financial Interests, Principal Investigator, PI of clinical trial: PharmaMar; Non-Financial Interests, Principal Investigator, PI OF Clinical Trial: Boehringher Ingelheim; Other, Travel, Accomodations Expenses For Scientific Meeting: Gentili, PharmaMar. E. Gonzalez Billalabeitia: Financial Interests, Personal, Invited Speaker: Astellas, Janssen, Bayer; Financial Interests, Personal, Advisory Board: Astra Zeneca, Pfizer; Financial Interests, Personal, Other, Travel Grant: Pfizer, Janssen; Financial Interests, Institutional, Coordinating PI, IIS Phase II Pembrolizumab in combination with Carboplatin and Cabazitaxel in AVPC: MSD; Financial Interests, Institutional, Research Grant, Translational research project in PTEN defective prostate cancer: AstraZeneca; Financial Interests, Institutional, Research Grant, Translational research grant for biomarkers associated with a clinical trial.: Janssen. J. Cruz Jurado: Financial Interests, Personal, Advisory Board: PharmaMar, Roche, Lilly, Pfyzer, Novartis, Gilead, AstraZeneca, Daiichi Sankyo, Seagen, GSK, Bayer, Deciphera, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: PharmaMar, Roche, Lilly, Pfyzer, Novartis, Eisai, Gilead, AstraZeneca, Daiichi Sankyo, Seagen, Esteve, Daiichi Sankyo; Financial Interests, Personal, Steering Committee Member: Roche. P. Ledesma: Financial Interests, Institutional, Officer, Chief Executive Officer: Sofpromed Investigacion Clinica, SL; Financial Interests, Institutional, Ownership Interest, Chief Executive Officer and Founder: Sofpromed Investigacion Clinica, SL; Financial Interests, Institutional, Other, Customer for CRO services: Karyopharm Therapeutics, Advenchen Laboratories, Philogen, Blueprint Medicines. D. Da Silva Moura: Financial Interests, Personal, Invited Speaker: Tecnofarma; Financial Interests, Personal, Stocks/Shares: Sarcoma Research Solutions; Other, Other, Funding related with flight and accommodation at scientific meetings.: PharmaMar. N. Hindi Muñiz: Financial Interests, Personal, Invited Speaker, Invited speaker: PharmaMar; Financial Interests, Personal, Advisory Board, Expert testimony: PharmaMar; Financial Interests, Personal, Other, Travel Grants/Inscriptions to Scientific Conferences: PharmaMar; Financial Interests, Personal, Other, Preceptorship: Tecnofarma; Financial Interests, Personal, Advisory Board, Participation in advisory board: Deciphera; Financial Interests, Institutional, Research Grant, Research grant for preclinical experiments: Immix BioPharma; Financial Interests, Institutional, Research Grant, Grant for preclinical studies: PharmaMar; Financial Interests, Institutional, Local PI, Clinical trial: Lilly; Financial Interests, Institutional, Other, SI clinical trial: Deciphera, INBRX therapeutics, Cebiotex, COGENT, PTC therapeutics, Phyllogen; Financial Interests, Institutional, Other, Subinvestigator: Adaptimmune, Karyopharm, GSK; Financial Interests, Institutional, Research Grant, Clinical trial and support for preclinical studies: Lixte; Financial Interests, Institutional, Other, Subinvestigator in clinical trial: Rain Therapeutics; Financial Interests, Institutional, Other, SI in clinical trial: Ayala Therapeutics, Boehringer Ingelheim; Financial Interests, Institutional, Other, SI of clinical trial: Abbisko; Non-Financial Interests, Member of Board of Directors, Member of Board of Directors: Spanish Group for Research on Sarcoma (GEIS); Non-Financial Interests, Other, Member of Coordination Team: SELNET Consortium; Non-Financial Interests, Member of Board of Directors, Member of Board of Directos and Educational Committee: CTOS; Non-Financial Interests, Member: ESMO, SEOM, ASCO, CTOS, EORTC. All other authors have declared no conflicts of interest.