Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Pembrolizumab (Keytruda), 200mg IV Q3W for a total of 2 administrations per patient, integrated into standard-of-care protocol prior to surgery. Based on the well-established time lines, the interval between diagnosis and standard of care hysterectomy is sufficient to treat patients with two cycles of pembrolizumab without interfering with standard of care.

Pembrolizumab (Keytruda)

Hans W Nijman, Prof. Dr.

An KL Reyners, Prof. Dr.

In this feasibility study the investigators intend to treat patients with high mutational uterine cancer with two cycles immune checkpoint inhibition before standard-of-care hysterectomy.

Objective:

The investigators aim to establish proof-of-concept for use of immune checkpoint blockade (ICB) as novel neo-adjuvant therapy in (deficient mismatch repair) dMMR and (Polymerase ε mutation)POLE-EDM uterine cancer (UC). When ICB proves to be feasible as defined in the primary endpoint, a follow-up with a larger multicenter studies to determine clinical efficacy, such as postponing standard-of-care surgery or randomized studies to standard-of-care.

Study design:

The investigators planned a window-of-opportunity study of ICB in primary dMMR UC (n=10) and primary POLE-EDM UC (n=10) patients. ICB (pembrolizumab; anti-PD1) will be administered in two cycles of 3 weeks between diagnosis and standard-of-care hysterectomy.

Tumor responses to pembrolizumab will be assessed 3 weeks after the second cycle of pembrolizumab by a pathologist (primary endpoint) and MRI (secondary endpoint).After treatment with immun checkpoint blockade a hysterectomy will take place (standard-of care). Peripheral blood and tumor samples will be used to evaluate immune responses.

Study population:

Primary dMMR/ POLE-EDM UC patients of any stage and/or grade who are intended to be treated with a hysterectomy recruited from the North-Netherlands oncological region.

Intervention: Pembrolizumab, 200mg IV Q3W for a total of 2 administrations per patient, integrated into standard-of-care protocol prior to surgery. Based on the well-established time lines, the interval between diagnosis and standard of care hysterectomy is sufficient to treat patients with two cycles of pembrolizumab without interfering with standard of care.

Main study endpoints:

The primary endpoint is the response rate of the tumor assessed by pathology in uterine cancer patients treated with neo-adjuvant pembrolizumab. The secondary endpoint is the objective response rate of the tumor by MRI using RECIST. Exploratory objectives are immunogenicity, safety and the value of a pipelle biopsy as a predictor for response.

A window-of-opportunity study of ICB in primary dMMR UC (n=10) and primary POLE-EDM UC (n=10) patients.

Neo-adjuvant Pembrolizumab in dMMR/ POLE-EDM Uterine Cancer Patients: a Feasibility Study

Collection of PBMC (60mL blood by vena puncture) before, during and after treatment to assess antigen specific T cell responses to mutation-associated neo-antigens

Adverse events will be documented according CTCAE.

The number of treatment-related surgical postponements will be counted to assess feasibility.

In order to assess the correlation of pathological response seen in the biopsy and the surgical specimen. A pipelle biopsy will be obtained during surgery and assess as the tumor specimen from hysterectomy in the primary endpoint.

Hematoxylin and eosin staining on endometrium tissue collected during standard-of-care hysterectomy will be assessed by an experienced pathologist for evidence of necrosis and/or viable tumor cells

Hematoxylin and eosin staining on endometrium tissue collected during standard-of-care hysterectomy will be assessed by an experienced pathologist for degree of immune infiltration.

Hematoxylin and eosin staining on endometrium tissue collected during standard-of-care hysterectomy will be assessed by an experienced pathologist for degrees of inflammation, fibrosis, and mucin, consistent with an ongoing immune response.

To assess the objective response rate of the tumor by MRI using RECIST1.1 in uterine cancer patients treated with 2 cycles neo-adjuvant pembrolizumab

Merck Sharp & Dohme LLC

University Medical Center Groningen

Principal Investigator

Symptoms and General Pathology

Respiratory Tract (Lung and Bronchial) Diseases

Death

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Micronutrients

Hematinics

Vitamins

Carboplatin

Pemetrexed

Immunomodulating Agents

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Folinic Acid

Folate

Vitamin B9

Drug: IO102 100µg administered subcutaneously (SC) on Day 1 of each 3 week cycle PLUS Drug: pembrolizumab (Keytruda) 200 mg intravenous (IV) infusion on Day 1 of each 3 week cycle

Drug: pembrolizumab (Keytruda) 200 mg IV infusion on Day 1 of each 3 week cycle

Drug: IO102 100µg SC on Day 1 of each 3 week cycle PLUS Drug: pembrolizumab (Keytruda) 200 mg IV on Day 1 of each 3 week cycle PLUS Drug: carboplatin (Carboplatin Kabi) at a target AUC of 5 mg/mL IV infusion on Day 1 of each 3 week cycle for a max of 4 administrations PLUS Drug: pemetrexed (Pemetrexed Alvogen) at 500 mg/m2 IV infusion on Day 1 of each 3 week cycle

Drug: pembrolizumab (Keytruda) 200 mg IV on Day 1 of each 3 week cycle PLUS Drug: carboplatin (Carboplatin Kabi) at a target AUC of 5 mg/mL IV infusion on Day 1 of each 3 week cycle for a max of 4 administrations PLUS Drug: pemetrexed (Pemetrexed Alvogen) at 500 mg/m2 IV infusion on Day 1 of each 3 week cycle

IO102

pembrolizumab (Keytruda)

Carboplatin (Carboplatin Kabi)

Pemetrexed (Pemetrexed Alvogen)

James Spicer, MD Prof

The purpose of this study is to determine if IO102 combined with pembrolizumab with or without chemotherapy is safe tolerable and effective in the treatment of Non-small Cell Lung Carcinoma (NSCLC).

The hypothesis is that IO102 will improve the objective response rate (ORR) in patients with metastatic NSCLC.

IO102 With Pembrolizumab, With or Without Chemotherapy, as First-line Treatment of Metastatic NSCLC

An Open-label, Randomized, Phase I/II Trial Investigating the Safety and Efficacy of IO102 in Combination With Pembrolizumab, With or Without Chemotherapy, as First-line Treatment for Patients With Metastatic Non-Small Cell Lung Cancer

All unpublished information relating to this trial and/or to the trial treatments is considered confidential by the Sponsor and shall remain the sole property of the Sponsor.

The Investigator must accept that the Sponsor may use the information from this clinical trial in connection with the development of the IO102, and therefore, may disclose it as required to other Investigators, to government licensing authorities, to regulatory agencies of other governments, stock exchange market, and commercial partners.

Dose Limiting Toxicity graded per Common Terminology Criteria for Adverse Events (CTCAE) version 4.03

Objective Response Rate (ORR) evaluated by RECIST 1.1 and defined as the rate of complete response (CR) + partial response (PR)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Neo-adjuvant Pembrolizumab in dMMR/ POLE-EDM Uterine Cancer Patients: a Feasibility Study	NCT04262089	Uterine Cancer	Pembrolizumab (...	18 Years -	University Medical Center Groningen
Neo-adjuvant Pembrolizumab in dMMR/ POLE-EDM Uterine Cancer Patients: a Feasibility Study	NCT04262089	Uterine Cancer	Pembrolizumab (...	18 Years -	University Medical Center Groningen
IO102 With Pembrolizumab, With or Without Chemotherapy, as First-line Treatment of Metastatic NSCLC	NCT03562871	NSCLC	IO102 pembrolizumab (... Carboplatin (Ca... Pemetrexed (Pem...	18 Years -	IO Biotech

Spots Global Cancer Trial Database for pembrolizumab (keytruda)