Presidents, Rock Stars and Companion Diagnostics: 2016 Review of Immunotherapy

President Jimmy Carter announced this spring that he no longer needed treatments for the metastatic melanoma found in his brain–after treatment with pembrolizumab (Keytruda, Merck), his physicians could no longer detect the cancer. In 2016, high-profile success stories, the inclusion of immunotherapy initiatives in Vice President Joe Biden’s Cancer Moonshot and new therapy options drew attention to immunotherapy, and for maybe the first time scientists considered the possibility of using the word cure when speaking about cancer treatment.

“No recent advance has been more transformative than the rise of immunotherapy, particularly over this past year,” said Julie M. Vose, MD, MBA, FASCO, ASCO President, in a recent article on Cancer.Net.  “These new therapies are not only transforming patient lives, they are also opening intriguing avenues for further research.”

Here we’ll review the year’s progress, setbacks and surprises in the field of immunotherapy and give our forecast for 2017.

FDA Approvals and Studies

There was no shortage of exciting news regarding FDA approvals for immunotherapies.

  • Pembralizumab (Keytruda, anti-PD-1 monoclonal antibody developed by Merck) received approval for additional indications as a single agent for recurrent or metastatic head and neck cancer[1] and first line-treatment for patients with certain types of non-small cell lung cancer (NSCLC).[2] For the target NSCLC patient population (high levels of PD-L1), single agent Keytruda resulted in improved survival over standard chemotherapy regimens.
  • Nivolumab (Opdivo, anti-PD-1 monoclonal antibody developed by Bristol-Myers Squibb) also added indications as a single agent to its label including refractory Hodgkin Lymphoma[3] and recurrent or metastatic head and neck cancer[4].
  • The first combination of two immuno-oncology drugs (Opdivo and the anti-CLTA-4 antibody ipilumimab, Yervoy, also commercialized by Bristol-Myers Squibb) was approved under accelerated approval by the FDA for the treatment of patients with BRAF V600 wild-type and BRAF V600 mutation-positive unresectable or metastatic melanoma.[5]
  • Atezolizumab (Tecentriq, anti PD-L1 monoclonal antibody developed by Roche) entered the market following FDA approvals in advanced or metastatic urothelial cancers[6] (first drug approved in this disease in decades) and in second line treatment of special types of NSCLC.[7]
  •  With these advancements, the list of solid tumors that these drugs are now approved to treat include: melanoma, renal cell carcinoma, HNSCC, urothelial cancer and NSCLC.

In addition to these more traditional approvals, the FDA appears to be getting more comfortable with exploring alternative study designs. For example, Merck recently filed its immunotherapy Keytruda in the U.S. as a potential therapy for previously treated patients with advanced microsatellite instability-high cancer—a condition that refers to a deficiency in a cell’s ability to repair errors in the DNA sequence that occur during cell division. The FDA is reviewing the drug under its Accelerated Approval program and has assigned the submission a priority review, which means that the company should have a decision by March 8.[8] If approved, Keytruda will be the first immuno-oncology drug indicated for a specific molecular alteration spanning different tumor types.

Based on currently ongoing studies, more approvals are expected in 2017 for Opdivo, Tecentriq and Keytruda as well as new comers, like durvalumab (anti-PD-L1 monoclonal antibody developed by Astra Zeneca).

Combination Therapies

This year, efforts towards combining immunotherapies–or supplementing them with traditional treatments like chemotherapy and radiation therapy–also started to pay off.

As mentioned above, in 2016 we witnessed the first approval of the combination of two immunotherapeutic agents (Opdivo and Yervoy) in first line metastatic melanoma. Although the combination was shown to be quite effective, it also increased the frequency and severity of autoimmune side effects, thus requiring careful risk-benefit considerations at the level of the single patient (and patient selection tools).[9]

Preliminary results from combining Keytruda with an IDO inhibitor in metastatic melanoma were particularly promising, showing impressive synergistic activity without increased toxicity. The combination received extra recognition for successfully treating the rock star Rikki Rocket, drummer for the band Poison.[10] In addition, combining Keytruda and chemotherapy in the first-line lung cancer treatment setting also provided initial evidence that the combination may increase response rates and open new treatment paths for a broader range of patients with advanced NSCLC.[11]

Currently more than 800 clinical trials listed on are testing immuno-oncology combinations. In 2017, expect to see more results from combination therapy studies for a better understanding of the benefits and toxicity that accompany combined approaches.

CAR T-cell Immunotherapy

CAR-T approaches, where T-cells are modified to identify tumor cells, were shown to have important clinical activity in certain B-cell hematologic malignancies.[12] Kite Pharma and Novartis will file for FDA approval soon as they have demonstrated impressive results from their CAR-T therapies in hematologic malignancies.[13]

However, concerns about toxic side effects continue to cloud this emerging form of immunotherapy, particularly in the wake of Juno Therapeutics’ halted CAR-T trial,[14] which has been plagued by patient deaths from neurological side effects. There is additional skepticism stemming from pricing uncertainties in this increasingly competitive landscape of hematologic cancer treatment and difficulties in getting CAR-T to work for solid tumors.

Companion Diagnostics

Companion diagnostics and the value of patient selection in drug development gained attention when two studies assessing the efficacy of two different monoclonal antibodies with similar mechanisms of action (i.e. anti-PD-1 antibodies), Keytruda and Opdivo, for the first line treatment of patients with advanced NSCLC, produced sharply different outcomes when compared to standard of care chemotherapy.

In the case of the Keytruda Keynote-024 trial, only patients with a tumor that had more than 50 percent of cells expressing PD-L1 were included in the trial. For that pre-selected population, single agent Keytruda showed to improve survival over standard chemotherapy, leading to FDA approval for Keytruda as a first-line treatment for NSCLC for that population.[2] However, surprisingly, the Opdivo CheckMate 026 trial failed to demonstrate a benefit over standard chemotherapy.[15]

A crucial difference between the two study designs was the biomarker enrichment strategy: unlike the Keynote-024 study, CheckMate 026 enrolled previously untreated patients with NSCLC who had ≥ 1 percent PD-L1 expression and pre-specified a conservative 5 percent PD-L1 cut-off to define their primary analysis population. This contrast in trial designs and outcomes brought attention to the value of companion diagnostic tests, like those created by NanoString Technologies, Inc., in the successful development of immuno-oncology drugs.

Efforts are ongoing in both industry and academia to develop predictive biomarkers that improve on currently approved PD-L1 tests. Several biomarkers are currently embedded in pivotal trials which could mature in 2017.

Find more information on tools for researching biomarkers that may form the basis for companion diagnostics.


  1. Inman, S. “FDA Approves Keytruda for Head and Neck Cancer,” Cure Today, August 5, 2016, LINK.
  2. Merck. (2016). FDA Approves Merck’s Keytruda (pembrolizumab) in Metastatic NSCLC for First-Line Treatment of Patients Whose Tumors Have High PD-L1 Expression With No EGFR or ALK Genomic Tumor Aberrations [Press release]. Retrieved from
  3. Broderick, J.M. “FDA Approves Opdivo for Classical Hodgkin Lymphoma,” Cure Today, May 17, 2016, LINK.
  4. Broderick, J.M. “Opdivo Approved in Head and Neck Cancer Subset,” Cure Today, November 10, 2016, LINK.
  5. Broderick, J.M. “FDA Approves Frontline Opdivo for BRAF-Mutant Melanoma,” Cure Today, January 25, 2016, LINK.
  6. FDA. (2016). FDA Approves New, Targeted Treatment for Bladder Cancer [Press release]. Retrieved from
  7. Roche. (2016). FDA Approves Roche’s Cancer Immunotherapy Tecentriq (atezolizumab) for People With a Specific Type of Metastatic Lung Cancer [Press release]. Retrieved from
  8. Broderick, J.M. “Keytruda Granted a Priority Review by the FDA for Advanced Microsatellite Instability-High (MSI-H) Cancer,” Cure Today, November 28, 2016, LINK.
  9. Inman, S. “Immunotherapy Combination Shows Promise in High-Risk Melanoma,” Cure Today, November 8, 2016, LINK.
  10. Staton, T. “Now Cancer-free After Keytruda Combo, Poison Drummer Rikki Rockett Ready to Spread the Word,” FiercePharma, July 20, 2016, LINK.
  11. Martins, I. “Keytruda, Chemotherapy Combo Shown as Promising First Line Therapy for Advance NSCLC,” Lung Cancer News Today, October 25, 2016, LINK.
  12. Park, J.H, et. al, Blood, 2016, doi:
  13. Adams, B. “Rivals Kite and Novartis Post New CAR-T Data as Both Plot FDA Approval,” FierceBiotech, December 5, 2016, LINK.
  14. Garde, D. “Two Patient Deaths Halt Trial of Juno’s New Approach to Treating Cancer,” STAT News, November 23, 2016, LINK.
  15. European Society for Medical Oncology. (2016). Greater Patient Selection May be Needed for First Line Nivolumab to Improve Progression-free Survival in Advanced Lung Cancer [Press release]. Retrieved from
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