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Pembrolizumab · 3 trials · 3 indications
Overall survival (OS) is defined as the time from randomization to death due to any cause
To compare OS in subjects treated with TTFields concomitant with pembrolizumab and platinum-based chemotherapy compared to OS of those treated with pembrolizumab and platinum-based chemotherapy alone (superiority analysis).
To compare PFS per RECIST v1.1 as assessed by BICR, in subjects treated with TTFields concomitant with pembrolizumab and platinum-based chemotherapy compared to PFS of those treated with pembrolizumab and platinum-based chemotherapy alone (superiority analysis)
Time from enrollment to progression or death or censoring, whichever occurs first. The study team will use the one-sample log-rank test to compare PFS in the triple combination arm relative to the historical control arm to determine whether the triple combination treatment increases PFS in newly diagnosed GBM patients when compared to TTFields+TMZ historical control patients from the EF-14 study. Evaluability for progression free survival required participants to receive adjuvant TMZ, Optune and at least 1 dose of pembrolizumab.
| Arm | Type | Description |
|---|---|---|
| Treatment Group | EXPERIMENTAL | - |
| Control Group | PLACEBO_COMPARATOR | - |
| Arm 1: NovoTTF-200T, Pembrolizumab, and Platinum-based Chemotherapy | EXPERIMENTAL | Subjects in this arm receive three treatments - TTFields using the NovoTTF-200T device, pembrolizumab, and platinum-based chemotherapy. |
| Arm 2: Pembrolizumab and Platinum-based Chemotherapy | ACTIVE_COMPARATOR | Subjects in this arm receive two treatments - pembrolizumab and platinum-based chemotherapy. |
| Optune System combined with Temozolomide (TMZ) + Pembrolizumab | EXPERIMENTAL | Patients with newly-diagnosed GBM who undergo maximal safe resection (biopsy alone is eligible) followed by chemoradiation consisting of concomitant TMZ daily and radiation therapy (RT) with minimal RT will be eligible for this trial. Four to six weeks after finishing chemoradiation, patients will start monthly cycles of adjuvant TMZ. Treatment with Optune will start at approximately the same time as the first cycle of adjuvant TMZ and continue until second disease progression or a maximum of 2 years. Within one week after starting Cycle 2 of adjuvant TMZ and Optune therapy, patients will begin open-label treatment with pembrolizumab every 3 weeks until first disease progression or unacceptable toxicities or 2 years, whichever comes first. |
| Historical Control | OTHER | Historical control of patients treated with Optune System combined with Temozolomide alone from the EF-14 study will be compared with the Optune System combined with Temozolomide (TMZ) + pembrolizumab |
| Name | Type | Description |
|---|---|---|
| Optune® device | DEVICE | Optune® device delivering TTFields therapy at 200 kHz. |
| Temozolomide | DRUG | Temozolomide per approved labeling. |
| Pembrolizumab | DRUG | Pembrolizumab dose throughout this study is 200 mg IV Q3W for a maximum of 35 cycles. |
| Placebo | DRUG | Placebo (saline solution) dose throughout this study is 200 mg IV Q3W for a maximum of 35 cycles. |
| NovoTTF-200T | DEVICE | The NovoTTF-200T is a portable, battery operated system intended for continuous home use, which delivers TTFields at a frequency of 150kHz to the subject by means of insulated transducer arrays. TTFields physically disrupt the rapid cell division exhibited by cancer cells. The physical disruption induced by TTFields can lead to to downstream immunogenic cell death. |
| Platinum based chemotherapy | DRUG | Platinum-based chemotherapy is a standard chemotherapy regimen commonly used in the treatment of non-small cell lung cancer |
| Temozolomide (TMZ) | DRUG | Patients will begin treatment with adjuvant TMZ at least 4 weeks but no more than 6 weeks from last dose of concomitant temozolomide or radiation therapy (the latter of the two). A minimum of 6 and maximum of 12 cycles of adjuvant TMZ will be given depending on tolerability and toxicity. |
| Optune System | DEVICE | Patients will undergo 24-months of planned treatment with Optune therapy. |
Inclusion Criteria: 1. The participant (or legally acceptable representative) has provided documented informed consent for the study. 2. Be ≥ 18 years of age on day of providing informed consent. 3. Participant with new diagnosis of GBM according to World Health Organization (WHO) 2021 Classificati...
Pembrolizumab is an investigational oncology therapy being studied in glioblastoma and metastatic non-small cell lung cancer. In glioblastoma, it is evaluated in combination with temozolomide and Tumor Treating Fields. In metastatic non-small cell lung cancer, it is studied with platinum-based chemotherapy and Tumor Treating Fields. It is not approved for these uses.
Pembrolizumab targets PDCD1, also known as programmed cell death protein 1, and acts as an inhibitor of this target. By inhibiting PDCD1, it is designed to modulate immune responses in the tumor microenvironment. This mechanism is being investigated across multiple oncology indications.
Pembrolizumab is being developed by NovoCure Limited, a company traded on NASDAQ under the ticker NVCR. NovoCure is conducting clinical trials to evaluate the drug in combination with other therapies for glioblastoma and metastatic non-small cell lung cancer.
Pembrolizumab is in Phase 3 clinical development. Two Phase 3 trials are actively recruiting patients: one for metastatic non-small cell lung cancer and one for newly diagnosed glioblastoma. A Phase 2 trial for glioblastoma has completed enrollment but is still active.
Pembrolizumab is being studied in three clinical trials. NCT06216301 is a Phase 3 trial for metastatic non-small cell lung cancer. NCT06556563 is a Phase 3 trial for newly diagnosed glioblastoma. NCT03405792 is a Phase 2 trial for glioblastoma. All trials are active.
Pembrolizumab is the generic name for the drug marketed as KEYTRUDA. In the clinical trials listed, pembrolizumab is used as an add-on therapy to Tumor Treating Fields and chemotherapy. The trials are sponsored by NovoCure, which is evaluating pembrolizumab in combination regimens.