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2022-RA-638-ESGO Pembrolizumab with multimodal immunomodulation in chemotherapy-pretreated cervical, endometrial, and uterine cancer: the PRIMMO phase II trial
  1. Emiel A De Jaeghere1,
  2. Sandra Tuyaerts2,
  3. An MT van Nuffel3,
  4. Ann Belmans4,
  5. Kris Bogaerts4,
  6. Regina Baiden-Amissah5,
  7. Peter Vuylsteke6,
  8. Stéphanie Henry6,
  9. Xuan Bich Trinh7,
  10. Peter A van Dam7,
  11. Sandrine Aspeslagh2,
  12. Alex de Caluwé8,
  13. Eline Naert1,
  14. Diether Lambrechts9,
  15. An Hendrix10,
  16. Olivier de Wever10,
  17. Koen K van de Vijver11,
  18. Frédéric Amant12,
  19. Katrien Vandecasteele13 and
  20. Hannelore G Denys1
  1. 1Medical Oncology, Ghent University Hospital, Ghent, Belgium
  2. 2Medical Oncology, University Hospital Brussels, Brussels, Belgium
  3. 3Anticancer Fund, Strombeek-Bever, Belgium
  4. 4Biostatistics and Statistical Bioinformatics Centre (L-BioStat), KU Leuven, Leuven, Belgium
  5. 5Leuven Cancer Institute, Leuven, Belgium
  6. 6Department of Hemato-Oncology, Centre Hospitalier Universitaire Université Catholique de Louvain Namur (Sainte-Elisabeth), Namur, Belgium
  7. 7Department of Gynecologic Oncology and Senology, University Hospital Antwerp, Edegem, Belgium
  8. 8Department of Radiation Oncology, Jules Bordet Institute, Brussels, Belgium
  9. 9VIB-KU Leuven Center for Cancer Biology, Leuven, Belgium
  10. 10Laboratory for Experimental Cancer Research, Ghent University, Ghent, Belgium
  11. 11Department of Pathology, Ghent University Hospital, Ghent, Belgium
  12. 12Center for Gynecologic Oncology Amsterdam (CGOA), Netherlands Cancer Institute and Amsterdam Medical Center, Amsterdam, Netherlands
  13. 13Department of Radiation Oncology, Ghent University Hospital, Ghent, Belgium


Introduction/Background To decrease immunosuppression and enhance T-cell activation in the tumour microenvironment, we conducted an open-label, investigator-initiated, multicohort, phase II trial (NCT03192059) of pembrolizumab with multimodal immunomodulation.

Methodology Chemotherapy-pretreated patients were recruited into two experimental cohorts (cervical carcinoma or endometrial carcinoma) and one exploratory cohort (uterine sarcoma). Patients received an immunomodulatory five-drug cocktail consisting of low-dose cyclophosphamide, aspirin, lansoprazole, vitamin D, and curcumin starting two weeks before radioimmunotherapy (figure 1). Pembrolizumab, 200 mg/dose, was administered on day 1 of each 21-day cycle from day 15 onwards; one of the tumour lesions was irradiated (8Gyx3) on days 15, 17, and 19. The primary endpoint was objective response rate (irORR) per immune-related response criteria (irRC) at week 26; a lower bound of its 90% confidence interval (CI) of >10% in either experimental cohort was considered successful.

Results Fifty patients were enrolled and treated across the cohorts (cervical, n=18; endometrial, n=25; sarcoma=7). Pathology review revealed that 3/7 sarcoma patients had carcinosarcoma. At week 26, the irORR was 11.1% (90%CI, 2.0 to 31.0) in cervical cancer, 12.0% (90%CI, 3.4 to 28.2) in endometrial cancer, and 14.3% (90% CI, 0.7 to 52.1) in uterine (carcino)sarcoma. The best overall response rate per RECIST v1.1 was 22.2% (90%CI, 8.0 to 43.9), 12.0% (90%CI, 3.4 to 28.2), and 28.6 (90%CI, 5.3 to 65.9). Median PFS was 13.4 weeks (11.3 to 26.1), 13.1 weeks (13.1 to 19.4), and 34.3 weeks (95%CI, 5.6 to 77.9) (figure 2A-C). Grade≥3 treatment-related adverse events were reported in 10 (55.6%), 9 (36.0%), and 4 (57.1%) patients. Overall, there was one (2.0%) possible treatment-related death. Health-related quality of life was generally stable over time. Multi-parameter immune monitoring characterised the patients and revealed changes throughout study treatment.

Abstract 2022-RA-638-ESGO Figure 1
Abstract 2022-RA-638-ESGO Figure 2

Combined waterfall and swimmer plot of the (A) cervical cohort, (B) endometrial cohort, and © (carcino) sarcoma cohort. Each row (i.e., response bar + characteristics + swimmer lane) corresponds to one patient. Waterfall plot showing best percentage change from baseline in the sum of diameters of the target lesions best overall response is indicated by color coding of bars and includes assessment of target, nontarget, and new lesions. The dotted lines at -30% abd +20% indicate thresholds for partial Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1). Swimmer plot (event chart) for tumor response (response category indicated by color coding), progressive disease per RECIST v1.1, safety, time on study, and death. The solid lines at week 3 and week 26 indicate the first pembrolizumab dose and timing of the primary endpoint, respectively

Conclusion PRIMMO did not show sufficient evidence of a positive risk-to-benefit ratio to recommend a confirmatory phase III trial.

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