Phase II Study of Pembrolizumab in Combination With Cisplatin or Carboplatin and Pemetrexed as Induction Chemo+Immunotherapy in Resectable Epithelioid and Biphasic Pleural Mesothelioma (CHIMERA Study)
This is a prospective, open-label, multi-site Phase II trial of pembrolizumab in combination with pemetrexed and cisplatin or carboplatin as neo-adjuvant therapy followed by surgery and adjuvant pembrolizumab in patients affected by resectable stage I-IIIa chemonaïve epithelioid/biphasic pleural mesothelioma.
• Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of surgical resectable stage I-IIIA treatment-naïve epithelioid/biphasic pleural mesothelioma will be enrolled in this study.
• Diagnosis of epithelioid/biphasic pleural mesothelioma must be histologically confirmed, preferably by video-assisted thoracoscopic surgery (VATS).
• At screening, complete surgical resection of the mesothelioma must be deemed achievable, as assessed by a multidisciplinary evaluation.
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
• Measurable disease, defined as at least 1 lesion measured in two positions at three separate levels on transverse cuts of CT scan that is suitable for repeated assessment using modified Response Evaluation Criteria in Solid Tumours \[m-RECIST 1.1\] for pleural mesothelioma is preferred; however, inclusion of specific cases without measurable disease could be discussed with the medical monitor and during the multidisciplinary team discussion of the surgical centers.
• Histologically proved diagnosis of treatment-naive epithelioid/biphasic pleural mesothelioma.
• Surgical resectable disease \[stage I - II - IIIA (T1-3 - N0/1-M0) according to ninth TNM edition\].
• No previous surgical resection of mesothelioma.
• Archival tumor tissue sample or newly obtained \[core, incisional or excisional\] biopsy of a tumor lesion not previously irradiated has been provided. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Has adequate PFT defined as an FEV1 \>50% (of predicted normal volume) or ≥ 1.2 L/Sec and a DLCO \>40% of predicted normal value. Participants for whom DLCO measurements are not available will be deemed to have adequate oxygen transfer if pulse oximetry (O2 saturation) ≥90% room air.
• Have adequate organ function as defined in the following table (Table 3). Specimens must be collected within 10 days prior to the start of study intervention.