Abstract 1015P
Background
HBM4003 is a fully heavy-chain-only monoclonal antibody (mAb) to CTLA-4, which was engineered to deplete Treg cells by enhanced ADCC.
Methods
This is a first-in-human, phase I study to evaluate the safety, anti-tumor activity, PK/PD and recommended phase II dose of HBM4003. In part 1 (presented here), patients (pts) were enrolled into 3 dose levels (DL): 0.3mg/kg QW (28-day cycle), 0.45mg/kg Q3W (21-day cycle), and 0.6mg/kg Q3W (21-day cycle). Part 2 is a dose-expansion study.
Results
The study is ongoing. Twenty pts with advanced solid tumors have been treated at 4 Australian sites; 13 pts received ≥ 2 lines of systemic therapies and 8 received previous PD-1/PD-L1 mAb. The most common treatment-related AE (TRAE) of all grades was diarrhea (8[40%] pts), followed by colitis (5[25%] pts). Grade (Gr) 3 TRAEs are shown in the table. Table: 1015P
Grade (Gr) 3 TRAEs
| DL | N, Enrolled (n, evaluable) | Gr 3 TRAE n, % | Gr 3 Diarrhea * n, % |
| 0.3mg/kg QW | 7 (6) | diarrhea, 2, 28.6% | diarrhea, 2, 28.6% |
| 0.45mg/kg Q3W | 7 (6) | increased blood bilirubin and LFT increased**,1, 14.3% | 0 |
| 0.6mg/kg Q3W | 6 (6) | diarrhea, 4, 66.7% | diarrhea, 4, 66.7% |
*No associated colitis or typical pathological changes, resolved with standard steroid treatment **Total bilirubin increased from normal to Gr 3, and LFT increased from Gr 1 to Gr 3. Other TRAEs included pruritus (3 [15%] pts), rash (4 [20%] pts), and hyperhidrosis (1 [5%] pt); all were Gr 1 or 2. There was 1 DLT (0.3mg/kg QW) with Gr 2 colitis and Gr 3 diarrhea. TRAE leading to discontinuation occurred in 8 pts. No DLT was observed in the Q3W DL. No Gr 4 or Gr 5 TRAE was reported. Fourteen pts were evaluable for efficacy: 9 had SD as best response, whereas 1 pt had confirmed PR as best response [0.45mg/kg Q3W, HCC, pre-treated with sorafenib, lenvatinib, and anti-PD-1, with tumor shrinkage of 22.2% (Week 6), 48.9% (Week 12), 53.3% (Week 16), and 64.4% (Week 24); AFP also declined from 170 u/l to <10u/l at Week 24], and 1pt (0.3mg/kg QW, CRPC) had SD with a PSA response. HBM4003 demonstrated near dose-proportional PK and extended PD effect. Immunogenicity was low.
Conclusions
Preliminary results for HBM4003 are encouraging. At 0.45mg/kg Q3W, there was no DLT and no cases of grade 3 diarrhea. There was one confirmed PR. Hence 0.45mg/kg Q3W was selected as the RP2D for part 2.
Clinical trial identification
NCT04135261.
Editorial acknowledgement
Legal entity responsible for the study
Harbour BioMed US, Inc.
Funding
Harbour BioMed US, Inc.
Disclosure
J. Ji: Financial Interests, Institutional, Full or part-time Employment: HBM Holdings Limited. M.M. de Assis: Financial Interests, Institutional, Full or part-time Employment: HBM Holdings Limited. X. Chen: Financial Interests, Institutional, Full or part-time Employment: HBM Holdings Limited. X. Gan: Financial Interests, Institutional, Full or part-time Employment: HBM Holdings Limited. X. Tao: Financial Interests, Institutional, Full or part-time Employment: HBM Holdings Limited. R. Zuo: Financial Interests, Institutional, Full or part-time Employment: HBM Holdings Limited. G. Ross: Financial Interests, Personal, Full or part-time Employment, Director: Graham Ross Oncology Consulting Services Ltd; Financial Interests, Personal, Stocks/Shares, Former Employee: Roche; Financial Interests, Personal, Stocks/Shares, Wife - Spouse: Roche; Financial Interests, Personal, Stocks/Shares, Former Employee: AstraZeneca; Financial Interests, Institutional, Other, Consultant: HBM Holdings Limited. L. Lu: Financial Interests, Institutional, Full or part-time Employment: HBM Holdings Limited. All other authors have declared no conflicts of interest.