406P - Phase Ib safety and efficacy of nadunolimab/gemcitabine/carboplatin in mTNBC

Background

Nadunolimab (Nad; CAN04) is an ADCC-enhanced IgG1 antibody targeting IL-1 Receptor Accessory Protein (IL1RAP) expressed on tumor and stroma cells. Nad blocks downstream IL-1 signaling, including both IL-1α/β signaling. Nad has shown promising clinical activity in PDAC and NSCLC studies. Among breast cancer subtypes, TNBC has the highest IL1RAP expression. TRIFOUR is a phase 1b/randomized phase 2 trial to evaluate NadGC in mTNBC patients (pts). Preliminary safety and efficacy from the phase 1b dose-escalation are presented. Analysis of immunological biomarkers are ongoing.

Methods

Standard 3+3 dose-escalation design was used for phase 1b. mTNBC pts received NadGC on days 1 and 8, in cycles of 3 weeks. Two dose levels (DLs) of Nad (DL1=1 mg/kg; DL2=2.5 mg/kg) were evaluated with standard G (1000 mg/m2) and C (area under the curve 2 mg/mL/min). Nad DL2 was considered the target dose and further dose escalation was not planned.

Results

Phase 1b recruitment is completed with 15 stage IV female pts. Median age was 50 years (32-69), six pts (40%) were pre-/perimenopausal, 14 pts (93%) had visceral disease. BRCA1/2 was known in 47% and was wild type in all. All pts but one received prior (neo)adjuvant therapy; four pts had received platinum. 33% received NadGC as first-line for mTNBC. Overall, 13 patients were evaluable for the DLT period (3 DL1, 10 DL2). Two patients had DLT, both in DL2: one Grade (Gr) 3 febrile neutropenia and one delay >1 week in C2D1 due to Gr3 neutropenia. Gr3/4 AEs in >one pt were neutropenia 47%, thrombocytopenia 33%, anemia 20% and febrile neutropenia 13%. All were considered related by the investigator. At data cut-off, seven pts were still on treatment. Efficacy analysis was available in 12 pts with 1 CR and 5 PR; overall response rate 50% (95% CI: 21-79%).

Conclusions

Nadunolimab at 2.5 mg/kg plus standard G and C is well tolerated and shows promising antitumor activity. Neutropenia is the most frequent toxicity but does not limit treatment. The randomized phase 2 part is currently enrolling with the 2.5 mg/kg dose.Nadunolimab at 2.5 mg/kg plus standard G and C is well tolerated and shows promising antitumor activity. Neutropenia is the most frequent toxicity but does not limit treatment. The randomized phase 2 part is currently enrolling with the 2.5 mg/kg dose.

Clinical trial identification

NCT05181462.

Editorial acknowledgement

Legal entity responsible for the study

Cantargia AB.

Funding

This work was supported by Cantargia AB. It is performed in collaboration with the Spanish Breast Cancer Group (GEICAM).

Disclosure

S. Lopez-Tarruella Cobo: Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo, Gebro Pharma, Gilead, GSK, Lilly, Menarini_Stemline, Novartis, Pierre Fabre, Roche, Seagen; Non-Financial Interests, Personal, Member of Board of Directors: GEICAM, SEOM. A. Stradella: Financial Interests, Personal, Advisory Board, Advisory about CAPITELLO 291 trial: AstraZeneca; Financial Interests, Personal, Advisory Board, Advisory on new activities for residents: Novartis; Financial Interests, Personal, Invited Speaker, Trastu-Deruxtecan clinical case meeting: Daiichi; Financial Interests, Personal, Invited Speaker, meeting on new data on cyclin inhibitors: Novartis. P. Tolosa Ortega: Financial Interests, Personal, Invited Speaker: Novartis, Pfizer, Lilly, Seagen, AstraZeneca, Daiichi Sankyo and MSD; Financial Interests, Personal, Advisory Board: Novartis, Adamed, Seagen and Daiichi Sankyo; Financial Interests, Personal, Full or part-time Employment, Medical Advisor and Madical Monitor: SOLTI; Financial Interests, Institutional, Funding: Novartis. S. Antolín-Novoa: Financial Interests, Personal, Invited Speaker: Pfizer, Lilly, Novartis; Financial Interests, Personal, Advisory Board: Astra-Daiichi; Financial Interests, Personal, Expert Testimony: ROCHE. M. Santisteban Eslava: Financial Interests, Personal, Other, Travel expenses: iltenyi, Roche, Gilead, Daiichi Sankyo, Lilly; Financial Interests, Personal, Advisory Role: Gilead, Daiichi Sankyo, Pfizer, AstraZeneca, Novartis; Financial Interests, Personal, Research Grant: Genentech. A.L. Guerrero Zotano: Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Personal, Advisory Role: Pfizer, AstraZeneca, Pierre Fabre, Novartis, Exact Science, Stemline; Financial Interests, Personal, Speaker, Consultant, Advisor: Roche, MSD, Novartis, Pfizer, AstraZeneca, Daiichi Sankyo, Pierre Fabre, Exac Science. M. Ruiz Borrego: Financial Interests, Personal, Research Grant: Roche, AstraZeneca, Daiichi Sankyo, Pierre FABRE, PFIZER, Novartis, Gilead ; Financial Interests, Personal, Advisory Role: Daiichi Sankyo, Gilead, Pierre Fabre. N. Losic: Financial Interests, Personal, Full or part-time Employment: Cantargia AB; Financial Interests, Personal, Stocks/Shares: Cantargia AB. E. Jaensson Gyllenbäck: Financial Interests, Personal, Full or part-time Employment, Employee: Cantargia AB; Financial Interests, Personal, Stocks/Shares, Stock holder: Cantargia AB; Financial Interests, Personal, Other, IP: Cantargia AB. P. Skoog: Financial Interests, Personal, Full or part-time Employment, Full time Senior Scientist at Cantargia AB: Cantargia AB; Financial Interests, Personal, Stocks/Shares, Stocks and Options in Cantargia AB: Cantargia AB. H. Johansen Blanco: Financial Interests, Personal, Full or part-time Employment: Cantargia AB; Financial Interests, Personal, Stocks/Shares, 6101 stocks with Cantargia AB: Cantargia AB. I. Garcia Ribas: Financial Interests, Personal, Other, Medical advisor: Cantargia AB, Oncomatryx; Financial Interests, Personal, Stocks/Shares: Sanofi, Cantargia. All other authors have declared no conflicts of interest.