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Published on: February 7, 2021
Phase 2 study of pembrolizumab in patients with advanced rare cancers
Aung Naing1, Funda Meric-Bernstam2, Bettzy Stephen2
1Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA anaing@mdanderson.org.
Background:
Patients with advanced rare cancers have poor prognosis and few treatment options. As immunotherapy is effective across multiple cancer types, we aimed to assess pembrolizumab (programmed cell death 1 (PD-1) inhibitor) in patients with advanced rare cancers.
Methods:
In this open-label, phase 2 trial, patients with advanced rare cancers whose tumors had progressed on standard therapies, if available, within the previous 6 months were enrolled in nine tumor-specific cohorts and a 10th cohort for other rare histologies. Pembrolizumab 200 mg was administered intravenously every 21 days. The primary endpoint was non-progression rate (NPR) at 27 weeks; secondary endpoints were safety and tolerability, objective response rate (ORR), and clinical benefit rate (CBR).
Results:
A total of 127 patients treated between August 15, 2016 and July 27, 2018 were included in this analysis. At the time of data cut-off, the NPR at 27 weeks was 28% (95% CI, 19% to 37%). A confirmed objective response (OR) was seen in 15 of 110 (14%) evaluable patients (complete response in one and partial response in 14). CBR, defined as the percentage of patients with an OR or stable disease ≥4 months, was 38% (n=42). Treatment was ongoing in 11 of 15 patients with OR at last follow-up. In the cohort with squamous cell carcinoma (SCC) of the skin, the NPR at 27 weeks was 36%, ORR 31%, and CBR 38%. In patients with adrenocortical carcinoma (ACC), NPR at 27 weeks was 31%, ORR 15%, and CBR 54%. In the patients with carcinoma of unknown primary (CUP), NPR at 27 weeks was 33%, ORR 23%, and CBR 54%. In the paraganglioma-pheochromocytoma cohort, NPR at 27 weeks was 43%, ORR 0%, and CBR 75%. Treatment-related adverse events (TRAEs) occurred in 66 of 127 (52%) patients, and 12 (9%) had grade ≥3 TRAEs. The most common TRAEs were fatigue (n=25) and rash (n=17). There were six deaths, all of which were unrelated to the study drug.
Conclusions:
The favorable toxicity profile and antitumor activity seen in patients with SCC of skin, ACC, CUP, and paraganglioma-pheochromocytoma supports further evaluation of pembrolizumab in this patient population.
Trial Registration Number:
NCT02721732.
Insights
Pembrolizumab showed antitumor activity in advanced rare cancers. This immunotherapy demonstrated a favorable toxicity profile, supporting further investigation in patients with specific rare tumor types like skin SCC and ACC.
Area of Science:
- Oncology
- Immunotherapy
- Rare Cancers
Background:
- Advanced rare cancers present significant challenges with limited treatment options and poor prognoses.
- Immunotherapy has shown efficacy across various cancer types, prompting investigation in rare malignancies.
Purpose of the Study:
- To evaluate the efficacy and safety of pembrolizumab (a programmed cell death 1 (PD-1) inhibitor) in patients with advanced rare cancers.
- To assess the non-progression rate (NPR), objective response rate (ORR), and clinical benefit rate (CBR) of pembrolizumab treatment.
Main Methods:
- An open-label, phase 2 trial enrolled 127 patients with advanced rare cancers who had progressed on standard therapies.
- Pembrolizumab 200 mg was administered intravenously every 21 days across nine tumor-specific cohorts and one rare histology cohort.
- Primary endpoint was NPR at 27 weeks; secondary endpoints included safety, tolerability, ORR, and CBR.
Main Results:
- The overall NPR at 27 weeks was 28% (95% CI, 19% to 37%).
- An objective response rate (ORR) of 14% was observed, with a clinical benefit rate (CBR) of 38%.
- Notable activity was seen in squamous cell carcinoma of the skin (NPR 36%, ORR 31%), adrenocortical carcinoma (NPR 31%, ORR 15%), carcinoma of unknown primary (NPR 33%, ORR 23%), and paraganglioma-pheochromocytoma (NPR 43%, CBR 75%). Treatment-related adverse events occurred in 52% of patients, with 9% experiencing grade ≥3 events.
Conclusions:
- Pembrolizumab demonstrated antitumor activity in patients with advanced rare cancers, including specific subtypes like SCC of the skin, ACC, CUP, and paraganglioma-pheochromocytoma.
- The drug exhibited a favorable toxicity profile, supporting its further evaluation in these rare cancer populations.
- These findings suggest pembrolizumab as a potential therapeutic option for select patients with advanced rare cancers.
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