Abstract 796P
Background
Initial results of the single-arm, phase II trial (NCT04180995) showed neoadjuvant toripalimab (T) plus axitinib (A) in resectable MuM had pathologic responses rate (RR) of 28.6% (4/14, 2 pCR, 2pPR) with good tolerance. We presented the updated data of pathologic RR, RFS at 1.5-years and the multiplex immunohistochemistry (mIHC) analysis before and after surgery.
Methods
Eligible pts were aged 18 to 75 with histologically confirmed resectable MuM. As neoadjuvant therapy, pts received T 3 mg/kg Q2W plus A 5 mg BID for 8 weeks before surgery, then adjuvant T 3 mg/kg Q2W for 52 weeks after surgery. The primary end point is pathologic RR according to the International Neoadjuvant Melanoma Consortium (pCR+pPR). The secondary end point is RFS in ITT population. Tumor infiltrating lymphocytes were quantified by mIHC.
Results
From Aug 2019 to Oct 2021, 29 pts were included. Median age 62 years; M: F 27.6% : 72.4%; primary sites：10 femal genital, 10 anorectal, 5 esophagus, 3 nasal and 1 oral cavity in which 31.0% localized disease, 65.5% regional lymphatic disease, and 3.5% oligometastatic disease. Till last follow up of Apr 2022, 24 pts had received surgery (local excision 8.3%, wide excision 91.7% and 5 pts inoperable for distant metastasis during neoadjuvant therapy), the pathologic RR was 27.6% (8/29, 4 pCR & 4 pPR). With a median follow up time of 17.5 m, 21 pts got recurrence (62.1% distant metastasis, 10.3% local-regional recurrence)，the median RFS was 11.7 m（95% CI: 6.6-16.9 m）, and it was 13.0 m vs. 6.2 m in responder vs. non-responder respectively . The median OS has not been reached. Neoadjuvant therapy was tolerable with grade 3-4 treatment related AEs of 20.7% (liver dysfunction 10.3%, hyperglycemia 6.9%, hypertension 3.4%, dyslipidemia 3.4% and CK increased 3.4%). 16 pts (4 responder, 12 non-responder) with tumor tissue samples at baseline and after surgery were collected to perform mIHC, It showed significant increase of infiltrating CD3+ (P = 0.0063) and CD3+CD8+ (P = 0.0076) T cells after neoadjuvant therapy.
Conclusions
Neoadjuvant T plus A in resectable MuM showed promising pathologic responses with significantly increased infiltrating CD3+ and CD3+CD8+ T cells, which supports further investigation.
Clinical trial identification
NCT04180995.
Editorial acknowledgement
Legal entity responsible for the study
Peking University Cancer Hospital and Institute.
Funding
Beijing Municipal Administration of Hospitals Incubating Program (Code: PX2021046).
Disclosure
L. Si: Financial Interests, Personal, Advisory Board: MSD, Roche, Novartis, Shanghai Junshi Biosciences, Oriengene. J. Guo: Financial Interests, Personal, Advisory Board: MSD, Roche, Bayer, Novartis, Simcere Pharmaceutical Group, Shanghai Junshi Biosciences, Oriengene; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Leadership Role: CSCO. All other authors have declared no conflicts of interest.