Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Clinical Results

Immune checkpoint-targeted therapies have received FDA approvals in ten tumour types or categories of cancer between 2011 and 2017: MM, NSCLC, renal cell carcinoma (RCC), urothelial cancers, head and neck squamous cell carcinoma (HNSCC), Hodgkin lymphoma (HL), Merkel cell carcinoma (MCC), hepatocellular carcinoma, gastric cancer and a range of MSI-H cancers.


The only anti-CTLA-4-blocking antibody that has received FDA approval is ipilimumab in MM patients, first as monotherapy in 2011, and in combination with nivolumab in 2015. Approval was based on the pivotal data of the CheckMate 067 trial, with an objective response rate (ORR) of 72.1% with nivolumab plus ipilimumab versus 21.3% with ipilimumab alone and statistically significant updated OS results for the combination versus ipilimumab (not reached [NR] versus 19.9 months in the ipilimumab group). Similarly, first-line combination therapy with nivolumab and ipilimumab has recently demonstrated clinical benefit in patients with previously untreated advanced or metastatic RCC. Results from the phase III CheckMate 214 trial showed significant improvement in OS (NR versus 26 months) and progression-free survival (PFS) (11.6 months versus 8.4 months) compared with sunitinib in intermediate- and poor-risk patients with metastatic RCC. In advanced NSCLC, the phase I CheckMate 012 trial showed significant clinical benefit for this combination, with an overall response in up to 47% of the patients; a phase III trial (CheckMate 227) is currently ongoing to confirm these results. This combination is also currently being evaluated in patients with unresectable pleural mesothelioma, in the CheckMate 743 study. In patients with advanced MM and patients with relapsed malignant mesothelioma, tremelimumab failed to demonstrate significant survival benefits compared with standard-of-care (SoC) ChT and placebo, respectively. Recently, the combination of durvalumab and tremelimumab did not reach the PFS outcome primary endpoint in the MYSTIC study in first-line treatment for patients with metastatic NSCLC, while the OS analysis is still pending.


Nivolumab was first approved for patients with MM (CheckMate 066 and CheckMate 037) and for adjuvant therapy of resected stage III melanoma (CheckMate 238). Nivolumab is approved for patients with squamous (CheckMate 017) and non-squamous (CheckMate 057) NSCLC, RCC (CheckMate 025), HNSCC (CheckMate 141), urothelial carcinoma (CheckMate 275), dMMR metastatic colorectal cancer (CheckMate 142) and classical HL after failure of first-line therapies. Treatment in patients with HL must follow relapse after autologous haematopoietic stem cell transplantation and post-transplantation brentuximab vedotin (CheckMate 205 and CheckMate 039). Most surprisingly, in NSCLC, nivolumab failed to demonstrate its superiority over ChT in the randomised phase III study CheckMate 026, in first-line treatment of patients with tumours with PD-L1 tumour expression ≥5%. Of note, there was imbalance in terms of TMB level between the two therapeutic arms, which could have contributed to this negative result. Indeed, patients with a high TMB showed a higher ORR and PFS when treated with nivolumab compared with ChT, and the inverse was shown in patients with low TMB. Interestingly, there was no correlation between the level of tumour PD-L1 expression and TMB.

Like nivolumab, pembrolizumab has been approved as second-line treatment of refractory/relapsing MM, NSCLC (with PD-L1 >1%), HNSCC, classical HL, urothelial carcinoma and any solid tumour expressing MSI-H status. In previously untreated advanced or metastatic NSCLC, pembrolizumab has been approved for patients harbouring PD-L1 expression on at least 50% of tumour cells, with an ORR of 44.8% versus 27.8% in the ChT group, from the pivotal phase III KEYNOTE-024 trial. Also, the combination of pembrolizumab with carboplatin and pemetrexed is now a SoC for patients with metastatic NSCLC, irrespective of PD-L1 expression, based on the results of the KEYNOTE-021 study (ORR 55% versus 29%). Pembrolizumab has also been approved as first-line treatment of cisplatin-ineligible urothelial carcinoma patients, thanks to the results of KEYNOTE-052 (ORR of 29%).


Anti-PD-L1-blocking antibodies have also been approved in certain other tumour types, such as advanced bladder carcinoma for durvalumab and atezolizumab, based on the results of the phase III DANUBE and phase II IMvigor 210 trials, respectively. In patients with metastatic NSCLC, atezolizumab has been approved based on the results of the phase II POPLAR and phase III OAK trials with OS of 12.6 months versus 8.9 months for second-line treatment. Recently, durvalumab has shown statistically significant improvement in PFS (16.8 months versus 5.6 months) after chemoradiotherapy in patients with locally advanced NSCLC (PACIFIC trial). A third anti-PD-L1 agent, avelumab, was approved in 2017 as both second-line treatment of metastatic urothelial carcinoma and first-line treatment of metastatic MCC.

Predictive and Prognostic Biomarkers of Clinical Relevance Potential Future Developments

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.