Preliminary results from two independent, phase II clinical trials investigating a new PD-1 (programmed cell death protein 1)-based immune therapy for metastatic cervical cancer suggest potential new treatment options for a disease that currently has limited effective options and disproportionately impacts younger women.
Dr David O’Malley, of The Ohio State University Comprehensive Cancer Centre – Arthur G James Cancer Hospital and Richard J Solove Research Institute (OSUCCC – James), presented the preliminary study results at the European Society for Medical Oncology (ESMO) Virtual Congress 2020. O’Malley was the lead presenter for both trials, which were sponsored by Agenus Inc.
Each study involved more than 150 patients with recurrent or metastatic cervical cancer from cancer treatment centres across the US and Europe. All patients were previously treated with platinum-based chemotherapy as a first-line therapy. The two independent but consecutive phase II trials tested a new immune-based agent called balstilimab given alone or in combination with a second monoclonal antibody drug called zalifrelimab.
Balstilimab is part of a class of drugs called checkpoint inhibitors. These drugs target the PD-1 protein within cancer cells and act as an “on” switch to help the immune system recognise and destroy cancer cells that would otherwise go undetected. Zalifrelimab is a drug that delivers engineered molecules (monoclonal antibodies) that allow for improved immune response to attack cancer cells.
For the first study, 160 patients were treated with single-agent balstilimab, resulting in a 14% response rate in all treated patients and a 19% response rate in PD-L1 positive patients.
For the second study, 155 patients were treated with balstilimab given in combination with zalifrelimab, resulting in a 22% response rate in all patients and a 27% response rate in PD-L1 positive patients.
“These two studies represent the largest trials of immuno-oncology therapies in relapsed cervical cancer to date and show that balstilimab and zalifrelimab may present meaningful new therapies for patients with cervical cancer,” O’Malley says. “Advances in these agents offer renewed hope for patients who have limited treatment options. This is especially important because this disease disproportionately affects younger women.”
Background: Second line treatment for R/M CC continues to be a high unmet clinical need. We present data from 2 ph2 trials, of single-agent balstilimab (bal) and in combination with zalifrelimab (zal) in R/M CC.
Methods: Patients received single-agent bal 3mg/kg q2w (NCT03104699) or in combination with zal 1mg/kg q6w (NCT03495882) up to 2 yrs. The primary endpoint was objective response rates (ORR) assessed per RECIST 1.1 by independent review, secondary endpoints included safety and DOR.
Results: We treated161 & 155 pts in the bal and bal/zal, respectively with 160 & 143 pts had baseline measurable disease (modified ITT population). All pts previously received platinum-based treatment for their first line as per protocol. Squamous-cell cancer (SCC) (63% bal; 74% bal/zal) was the predominant histologic subtype with adenocarcinoma/adenosquamous/other (AC) also represented. PD-L1 positive was defined as CPS ≥ 1% (62% bal; 55% bal/zal), negative as CPS <1% (26% bal; 25% bal/zal) or unknown (12% bal; 20% bal/zal). Efficacy data are below.
Treatment was well tolerated in both trials. 49 (30%) pts had immune-related AEs in bal & 50 (35%) in bal/zal trial (all grades) and severe (Grade 3+) 13 (8.0%) and 15 (10.5%) respectively. Treatment discontinuation were seen in 22 pts (13.7%) in bal and 15 pts (10%) in bal/zal. There were no treatment related deaths on the bal trial and 2 in the bal/zal trial (nephritis; pneumonitis). No new safety signals were identified. Table: LBA34
Efficacy bal (160) N (%) bal/zal (143) N (%)
ORR 24 (14) 31 (22)
CR 3 (2) 8 (6)
PR 20 (12) 23 (16)
DOR (m) 15.4 [1.1+,15.4] NR [1.3+,16.6+]
SCC 18/100 (18) 28/106 (27)
AC 5/59 (8) 3/37 (7)
PD-L1 + 19/99 (19) 21/79 (27)
PD-L1 – 4/42 (10) 4/36 (11)
Unknown PD-L1 0/19 (0) 6/28 (21)
Conclusions: These results show that both single-agent bal and bal/zal are active and well tolerated in R/M CC. Adding bal to zal increased both ORR and DOR with marginal increase in AEs. Responses were more common in the PD-L1 + and SCC pts, but responses were seen in PD-L1-, AC pts. This is by far the largest reported study of checkpoint inhibitors in cervical cancer to date.
DM O’Malley, A Oaknin, BJ Monk, A Leary, F Selle, J Alexandre, LM Randal, C Rojas, M Neffa, A Kryzhanivska, L Gladieff, D Berton, T Meniawy, I Lugowska, I Bondarenko, KN Moore, WI Ortuzar Feliu, M Ancukiewicz, I Shapiro, IL Ray-Coquard
Ohio State University Wexner Medical Centre material
ESMO 2020 Virtual Conference abstract