Study of Pembrolizumab, Radiation and Immune Modulatory Cocktail in Cervical/Uterine Cancer

This is a Phase II study in patients with advanced and/refractory cervical cancer, endometrial carcinoma or uterine sarcoma. Patients will be treated with an immunomodulatory cocktail (Vitamin D, aspirin, Cyclophosphamide and Lansoprazole), followed by pembrolizumab, combined with radiation. In addition, patients will take Curcumin, a food supplement.

Sex

Female

Minimum age

18 Years

Inclusion Criteria:

* Have histologically confirmed endometrial carcinoma, cervical carcinoma or uterine sarcoma, refractory or persistent to chemotherapy or recurrent disease after at least one line of chemotherapy.
* Presence of an index lesion amenable to hypofractionated stereotactic radiotherapy
* At least one lesion outside the radiation field that can be followed by imaging for clinical response according to RECIST and irRC
* Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion before and after radiotherapy if technically feasible.
* Have a performance status of 0 or 1 or 2 on the ECOG Performance Scale.
* Demonstrate adequate organ function

Exclusion Criteria:

* Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
* Prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2 agent
* Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 2 weeks prior to the first dose of trial treatment,
* Known history of active TB (Bacillus Tuberculosis), Human Immunodeficiency Virus (HIV), HTLV or syphilis,non-infectious pneumonitis, has active autoimmune disease.
* Has active central nervous system metastases and/or carcinomatous meningitis

• DERIVEDBaiden-Amissah REM, Tuyaerts S, Annibali D, Herreros-Pomares A, De Wispelaere W, Benedetto RM, De Jaeghere EA, Van Nuffel AMT, Vuylsteke P, Henry S, Bich Trinh X, Van Dam PA, Aspeslagh S, De Caluwe A, Naert E, Vandecasteele K, Denys HG, Amant F. Circulating immune cell profiling in advanced cervical and endometrial cancer patients treated with PD-1 blockade, radiotherapy, and immune modulation in the PRIMMO trial. Front Immunol. 2026 May 21;17:1794131. doi: 10.3389/fimmu.2026.1794131. eCollection 2026. PMID 42253973
• DERIVEDDe Jaeghere EA, Hamerlinck H, Tuyaerts S, Lippens L, Van Nuffel AMT, Baiden-Amissah R, Vuylsteke P, Henry S, Trinh XB, van Dam PA, Aspeslagh S, De Caluwe A, Naert E, Lambrechts D, Hendrix A, De Wever O, Van de Vijver KK, Amant F, Vandecasteele K, Verhasselt B, Denys HG. Associations of the gut microbiome with outcomes in cervical and endometrial cancer patients treated with pembrolizumab: Insights from the phase II PRIMMO trial. Gynecol Oncol. 2024 Dec;191:275-286. doi: 10.1016/j.ygyno.2024.10.020. Epub 2024 Nov 7. PMID 39515198
• DERIVEDDe Jaeghere EA, Tuyaerts S, Van Nuffel AMT, Belmans A, Bogaerts K, Baiden-Amissah R, Lippens L, Vuylsteke P, Henry S, Trinh XB, van Dam PA, Aspeslagh S, De Caluwe A, Naert E, Lambrechts D, Hendrix A, De Wever O, Van de Vijver KK, Amant F, Vandecasteele K, Denys HG. Pembrolizumab, radiotherapy, and an immunomodulatory five-drug cocktail in pretreated patients with persistent, recurrent, or metastatic cervical or endometrial carcinoma: Results of the phase II PRIMMO study. Cancer Immunol Immunother. 2023 Feb;72(2):475-491. doi: 10.1007/s00262-022-03253-x. Epub 2022 Aug 12. PMID 35960332
• DERIVEDTuyaerts S, Van Nuffel AMT, Naert E, Van Dam PA, Vuylsteke P, De Caluwe A, Aspeslagh S, Dirix P, Lippens L, De Jaeghere E, Amant F, Vandecasteele K, Denys H. PRIMMO study protocol: a phase II study combining PD-1 blockade, radiation and immunomodulation to tackle cervical and uterine cancer. BMC Cancer. 2019 May 28;19(1):506. doi: 10.1186/s12885-019-5676-3. PMID 31138229