Abstract 906P
Background
Simlukafusp alfa (SIM; FAP-IL2v) is an interleukin-2 variant moiety fused to a human antibody against fibroblast activation protein-α (FAP). High affinity binding of SIM to FAP, expressed on cancer-associated fibroblasts, mediates its accumulation in malignant lesions. SIM retains binding affinity to IL-2 receptor βγ without binding to IL-2Rα resulting in activation of immune effector NK and CD8 T cells but not regulatory T cells. This phase I study evaluated potential enhancement of ADCC-competent antibody cetuximab (CET) by SIM in patients (pts) with head and neck squamous cell carcinoma (HNSCC) with prior ≥1 lines of treatment.
Methods
In the Dose escalation (DE), 21 pts received SIM 5-20 mg weekly (QW) for 4 weeks and every 2 weeks (Q2W) thereafter. In the Extension (n = 37), SIM was administered at the DE recommended 10 mg QW for 4 weeks and Q2W thereafter. CET was dosed at QW or Q2W schedules. Efficacy endpoints were: primary - ORR by RECIST v1.1, secondary - DCR, DoR.
Results
We enrolled 58 pts of which 50 were males. Median age was 61 years (range 39-79). Of the response-evaluable 46 pts, 34 had prior PD-(L)1 inhibitor (CPI), 28 prior CET, 21 both, 37 prior platinum based therapy. Median number of cycles was 9 (range 1-43). The ORR and DCR were 7% and 50%, respectively, with 4 partial responses, 25 stable diseases. All responders had prior CPI (4/34), and 1 responder also had prior CET (1/21). DoR ranges from 2.3 to 14.3 months. Grade 3-4 adverse events (AE) were reported in 79.3% pts. AEs led to SIM withdrawal in 5.2% pts and dose modification/interruption in 32.8% pts. Class-specific AEs (Gr 3-4) for SIM: Pyrexia, infusion related reaction, capillary leak syndrome and liver function test abnormalities, were reported in 65.5% (1.7%), 37.9% (15.5%), 0% and 34.5% (15.5%) pts, respectively. Gr5 AEs were reported in 2 pts, cardiac arrest and hemorrhage, neither related to study drug.
Conclusions
The safety profile of SIM in combination with CET was consistent with the safety of each component, and did not lead to unexpected overlapping toxicities. Despite exceptional responders with prior CPI, overall low anti-tumor activity does not warrant further clinical exploration in HNSCC.
Clinical trial identification
NCT02627274.
Editorial acknowledgement
Legal entity responsible for the study
F. Hoffmann-La Roche.
Funding
Hoffmann-La Roche.
Disclosure
A.R. Hansen: Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: GlaxoSmithKline; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Institutional, Research Grant: Karyopharm Therapeutics; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: Roche/Genentech; Financial Interests, Institutional, Research Grant: Janssen; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Macrogenics. C.A. Gomez-Roca: Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Invited Speaker: Roche/Genentech; Financial Interests, Institutional, Other, Coordinating PI: BMS; Other, Personal, Other, Steering Committee Member: BMS; Financial Interests, Personal, Other, Local PI: Foundation Medicine; Other, Personal, Other, Steering Committee Member: Genentech; Financial Interests, Institutional, Research Grant: Roche/Genentech; Non-Financial Interests, Other, officer: ESMO - MCBS Extended Working Group; Non-Financial Interests, Other, Officer: ESMO Membership Committee; Non-Financial Interests, Other, Member of Board of Directors: FITC (Société française d'Immuno-Thérapies du Cancer); Non-Financial Interests, Other, Young Investigators Committee at imCORE, officer: inFLAME; Non-Financial Interests, Other, Member of Board of Directors: OncoDistinct; Non-Financial Interests, Leadership Role: FITC (Société française d'Immuno-Thérapies du Cancer). M.P. Lolkema: Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: INCa; Financial Interests, Personal, Advisory Board: Janssen Cilag BV; Financial Interests, Personal, Other, Other, Consulting: Julius Clinical; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Servier; Financial Interests, Institutional, Research Grant: Astellas; Financial Interests, Institutional, Research Grant: Janssen; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Sanofi. L. Verlingue: Financial Interests, Institutional, Principal Investigator, principal/sub investigator: Abbvie, Adaptimmune, Aduro Biotech, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Arno Therapeutics, Astex Pharmaceuticals, AstraZeneca, Aveo, Basilea Pharmaceutica International Ltd, Bayer Healthcare Ag, Bbb Technologies Bv, Beigene, Blueprint Medicine; Financial Interests, Research Grant: AstraZeneca, BMS, Boehringer Ingelheim, Janssen Cilag, Merck, Novartis, Onxeo, Pfizer, Roche, Sanofi; Non-Financial Interests, Other, drug supplies: AstraZeneca, Bayer, BMS, Boringher Ingelheim, Medimmune, Merck, NH TherAGuiX, Onxeo, Pfizer, Roche. A. Italiano: Financial Interests, Funding, research support: AstraZeneca; Financial Interests, Funding, research support: Bayer; Financial Interests, Funding, research support: BMS; Financial Interests, Funding, research support: Merck Sharp and Dohme; Financial Interests, Funding, research support: Roche; Financial Interests, Funding, research support: Pharmamar; Financial Interests, Advisory Board: Bayer; Financial Interests, Advisory Board: Daiichi Sankyo; Financial Interests, Advisory Board: Epizyme; Financial Interests, Advisory Board: Ipsen; Financial Interests, Advisory Board: Merck Sharp Dohme; Financial Interests, Advisory Board: Roche; Financial Interests, Advisory Board: Springworks. J. Spicer: Financial Interests, Institutional, Other: Achilles; AstraZeneca; Bayer; BergenBio; Boehringer-Ingelheim; BMS; Celgene; Curis; Genmab; Roche; Shionogi; Starpharma; Taiho; Financial Interests, Institutional, Other, Research funding and honoraria: Achilles; Financial Interests, Institutional, Other, Research funding and honoraria: AstraZeneca; Financial Interests, Institutional, Other, Research funding and honoraria: Bayer; Financial Interests, Institutional, Other, Research funding and honoraria: BergenBio; Financial Interests, Institutional, Other, Research funding and honoraria: Boehringer-Ingelheim; Financial Interests, Institutional, Other, Research funding and honoraria: BMS; Financial Interests, Institutional, Other, Research funding and honoraria: Celgene; Financial Interests, Institutional, Other, Research funding and honoraria: Curis; Financial Interests, Institutional, Other, Research funding and honoraria Research funding and honoraria: Genmab; Financial Interests, Institutional, Other, Research funding and honoraria: Roche; Financial Interests, Institutional, Other, Research funding and honoraria: Shionogi; Financial Interests, Institutional, Other, Research funding and honoraria: Starpharma; Financial Interests, Institutional, Other, Research funding and honoraria: Taiho; Financial Interests, Other, Co-founder and shareholder: Epsilogen. N. Steeghs: Financial Interests, Advisory Role, consultation: AIMM Therapeutics, Boehringer Ingelheim, Ellipses Pharma; Financial Interests, Research Grant: AB Science, Abbvie, Actuate Therapeutics, Amgen, Array, AstraZeneca/MedImmune, Bayer, Blueprint Medicines, Boehringer Ingelheim, Bristol-Myers Squibb, Cantargia, CellCentric, Cytovation, Deciphera, Genentech/Roche, GlaxoSmithKline, Incyte, Lilly, Merck Sh. J.E. Bauman: Non-Financial Interests, Institutional, Other, Coordinating PI: AstraZeneca; Non-Financial Interests, Institutional, Other, Coordinating PI: Aveo; Non-Financial Interests, Institutional, Other, Local PI: Bristol Myers Squibb; Non-Financial Interests, Institutional, Other, Steering Committee Member: Celldex; Non-Financial Interests, Institutional, Other, Local PI: CUE Biopharma; Non-Financial Interests, Institutional, Research Grant: Lilly; Non-Financial Interests, Institutional, Other, Local PI: Moderna; Non-Financial Interests, Institutional, Research Grant: Novartis. J. Fayette: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Innate Pharma; Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Institutional, Other, Research Funding: Seagens; Non-Financial Interests, Principal Investigator: AstraZeneca. J. Niu: Financial Interests, Principal Investigator: Roche; Financial Interests, Institutional, Invited Speaker, Honoraria: Onclive; Financial Interests, Advisory Role: Boehringer Ingelheim, Merck, AstraZeneca, Blueprint Medicines, Immvira, Johnson & Johnson, Takeda, Exelexis, Beigene, Mirati Therapeutics. H. Prenen: Financial Interests, Institutional, Advisory Board: Amgen; Financial Interests, Institutional, Invited Speaker: Bayer; Financial Interests, Institutional, Invited Speaker: Ipsen; Financial Interests, Institutional, Invited Speaker: Lilly; Financial Interests, Institutional, Advisory Board: Lilly; Financial Interests, Institutional, Invited Speaker: Sanofi; Financial Interests, Institutional, Invited Speaker: Vifor pharma. D. Dejardin: Financial Interests, Personal, Full or part-time Employment: Roche; Financial Interests, Personal, Stocks/Shares: Roche. C. Boetsch: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche. A. Kraxner: Financial Interests, Institutional, Full or part-time Employment: Roche; Financial Interests, Personal, Stocks/Shares: Roche. S. Evers: Financial Interests, Personal, Full or part-time Employment: Roche; Financial Interests, Personal, Stocks/Shares: Roche. T. Vardar: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche. N. Keshelava: Financial Interests, Personal, Stocks/Shares: Roche; Financial Interests, Personal, Stocks/Shares: Jazz Pharmaceutical; Financial Interests, Personal, Full or part-time Employment: Roche. V. Teichgräber: Financial Interests, Personal, Full or part-time Employment: Roche; Financial Interests, Personal, Stocks/Shares: Roche. All other authors have declared no conflicts of interest.