Profiles in GU Oncology: Jérémie Calais, MD, PhD

Dr Jérémie Calais is Director of the Theranostics Program and of the Clinical Research Program in the Ahmanson Translational Theranostics Division and Associate Professor in the Department of Molecular and Medical Pharmacology (DMMP) at the University of California, Los Angeles (UCLA). He leads a clinical research program of nuclear medicine and theranostics, combining radionuclide imaging and therapy. The program has been primarily involved in conducting clinical trials to determine the impact of prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging and PSMA radionuclide therapy on care and outcome of patients with prostate cancer. Dr Calais is especially well known for his work on 68Ga-PSMA–11, the first PSMA PET agent to receive regulatory approval for prostate cancer imaging in the US in 2020.¹ Originally developed by the University of Heidelberg, clinical development of 68Ga-PSMA–11 on which approval was based, was carried out by Dr Calais and colleagues at UCLA and researchers at the University of California, San Francisco (UCSF).^2,3

From France to the US

Dr Calais joined UCLA from Paris in France in 2016. He admits that when he first arrived in the US, he was not anticipating staying for very long. He was looking forward to spending one or two years living a new adventure abroad and working outside his “comfort zone,” he says. That he ended up staying longer than he intended was due to “pure luck and opportunism,” he told GU Oncology Now, during an interview about his life and career to date. The luck was that he fell in love with the outdoor lifestyle that Santa Monica offered him, and the opportunity was that he was offered to lead exciting professional projects as he arrived right just at the time of the theranostics booming in the US.

Growing up in France, Dr Calais had no family connections with professional medicine, and his early ambition was to just play soccer. “I played at competitive, non-professional level and it was a big part of my life for many years,” he recalls. Besides sports, he was also good at science, particularly biology, in school. “So when I realized that I needed to do something in my life other than playing soccer, I decided to go for medicine,” he says. “At first, he intended to specialize in sports medicine. In 2003, he started his first year of medical school at Paris Diderot University (now Paris Cité University). “In France you enter medical school straight after high school, much earlier than in the US,” he explains. “After the first year there is a ranking exam, the result of which determines whether you can progress to the second year.” Only 10-20% of candidates pass this exam, “so anyone can get into the first year of medical school, but to get past that and into the second year is tough,” he notes.

It takes much longer to qualify in medicine in France than in the US. Six years are spent at medical school, the last three years in attendance at a hospital attached to the university, which for Dr Calais was the Faculty of Medicine Xavier Bichat (named after Marie François Xavier Bichat, 1771-1802, known as “the father of modern histology”). A medical internship (residency) of 4 years followed at the University of Rouen School of Medicine and at the Henri Becquerel Cancer Center. In 2014, Dr Calais completed his internship and successfully defended his medical thesis (on FDG uptake in PET/CT in non-small cell lung and esophageal cancers treated with radiation therapy). In the same year, he was awarded the Diplôme d’Etat de docteur en médecine (DE), and became board certified by the French Society of Nuclear Medicine. Dr Calais spent two more years in Paris to get more training, choosing to specialize in nuclear oncology. He also obtained an MSc in biomedical imaging from the University of Paris-Sud (now Paris-Saclay), the equivalent to the first 2 years of a PhD in the US. He did not complete his PhD because in 2016, he moved to UCLA, which he calls “the start of a new adventure.”

Dr Calais explains why he made the move. “The life of a doctor can be sometimes linear,” he says. “After you are done with your training, you usually get a long-term position, either in private practice or public hospital and you follow the track. I was seeking a non-linear pathway and wanted to have a little bit of adventure outside of my ‘doctor career’ life in France by going abroad before moving to a more long-term position with 10 to 20 years of commitment in one place.” “I wanted to experience something different than Paris, but with a professional project that would still advance my clinical career,” Dr Calais adds. He believes that the way physicians are trained in France, “the clinical knowledge we have,” makes it easy for them to adapt to working in other countries.

Language ability restricted where he could go, however. “I was able to speak a little English at that time, but no other languages, so it had to be an English-speaking country.” And as he and his wife were both Parisians “with a really strong network and a great quality of life in Paris,” they preferred to relocate to another large city. “There were only a few cities my wife would have followed me to in the US: New York, Los Angeles, San Francisco, Chicago, Miami and that’s probably it,” he admits. “Los Angeles is different from Paris but is still a great city to live in and we’re very happy here,” he says.

Career Moves: From Theranostics to Radioligand Therapies

Dr Calais was already in contact with his mentor at UCLA, Johannes Czernin, MD, Chief of the Ahmanson Translational Theranostics Division, Professor of Molecular and Medical Pharmacology/Nuclear Medicine. Dr Czernin himself had relocated from Europe when he moved from the University of Vienna to UCLA in 1989. Dr Calais was appointed assistant professor in his department. “I arrived at the time of the rise of new theranostics techniques, focused mostly on PSMA,” Dr Calais recalls. He worked first with colleagues from Germany, Drs Wolfgang Fendler, Ken Herrmann and Matthias Eiber, who eventually had to return home. “Dr Czernin wanted to develop PSMA PET and therapy and our German colleagues were instrumental in starting things up here, based on their expertise from Germany. Then PSMA PET works so well and the technique is so effective that referring physicians were sending us more and more patients and it became quite big very rapidly, so there was a real need for someone to handle all the new work,” Dr Calais explains.

Dr Calais was appointed to his current position of director of clinical research program in 2018. He attributes this to “the combination of the opportunity, my being there at the right time, the emergence of this new, practice-changing technology, and my doing a good job at using it, selling it to physicians, and planning.” “Dr Czernin gave me a lot of confidence and, gradually, a lot of projects,” he acknowledges. “Things went very well for me. We did about ‘5000’ PSMA PET 68Ga PSMA-11 scans in 4 years and the FDA approval was a whole new adventure. We initiated many clinical trials to answer many clinical questions.”

He also worked on 177Lu-PSMA-617 (Pluvicto, Novartis), the first targeted radioligand therapy approved for treatment of PSMA-positive metastatic castration-resistant prostate cancer.⁴ “There are still many clinical questions that we are trying to answer to improve the use of PSMA-targeted imaging and therapy,” Dr Calais admits. “What are the best thresholds, what are the best indications, what do you do with that information? Maybe one day we will have the same questions in other diseases with other targets using similar approaches,” he suggests. “We’re not there yet, and that’s exactly why we’re doing these studies.”

Dr Calais appreciates the way research in the life science environment is conducted in the US. “You benefit from the whole US university resource and financial support and power that you get here,” he says. “You get many more initiatives, credits, and resources to be a health care researcher. Innovation is rewarded with money by industry. That is why the US is attractive for researchers, and people come here,” he declares. For the future in his field, Dr Calais hopes to see more applications of artificial intelligence (AI) tools in PET imaging. He is confident that it will further refine the ability to more accurately identify and stage prostate cancer and locate metastases; it will be used as an imaging biomarker to help guide therapy. Dr Calais has been working with PYLARIFY AI™ (Lantheus), the first AI platform approved by the US FDA in 2021.⁵ It uses a deep learning algorithm to assist in standardized quantification of prostate cancer images acquired using PSMA PET/CT.

Dr Calais is also looking at the promise of new radionuclide agents for treatment of prostate cancer and neuroendocrine tumors such as additional lutetium PSMA beta-emitters like 177Lu-PNT2002 (177Lu-PSMA-I&T), 177Lu-rhPSMA-7.3, and 177Lu-rhPSMA-10.1. Actinium and lead-labelled alpha-emitting agents including 225Ac-PSMA-617 and 212Pb-NG001 are in development. High-energy, short-range emissions will be able to pinpoint tumor targeting more efficiently, he explains. As to the future in his personal life, Dr Calais says his family is now settled in Santa Monica, He and his wife now have a Santa Monica-born daughter, in addition to their son. “We love it here; we love the lifestyle, the weather, the outdoors,” he declares. “We’re always at the beach or hiking, and we love visiting all the national parks in the US.” He likes the water, he loves his bike, he does triathlons…and he still plays soccer.

Linda Brookes, MSc is a freelance medical writer/editor based in New York and London.

References

1. FDA approves first PSMA-targeted PET imaging drug for men with prostate cancer. Food and Drug Administration; December 1, 2020. Accessed July 10. https://www.fda.gov/news-events/press-announcements/fda-approves-first-psma-targeted-pet-imaging-drug-men-prostate-cancer
2. Fendler WP, Calais J, Eiber M et al. Assessment of 68Ga-PSMA-11 PET accuracy in localizing recurrent prostate cancer: a prospective single-arm clinical trial. JAMA Oncol. 2019;5(6):856-863. DOI: 10.1001/jamaoncol.2019.0096
3. Hope TA, Eiber E, Armstrong WR, et al. Diagnostic accuracy of 68Ga-PSMA-11 PET for pelvic nodal metastasis detection prior to radical prostatectomy and pelvic lymph node dissection: a multicenter prospective phase 3 imaging trial. JAMA Oncol. 2021;7(11): 1635-1642. DOI 10.1001/jamaoncol.2021.3771
4. FDA approves Pluvicto for metastatic castration-resistant prostate cancer. Food and Drug Administration; March 23, 2022. Accessed July 10. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pluvicto-metastatic-castration-resistant-prostate-cancer
5. FDA authorizes software that can help identify prostate cancer. Food and Drug Administration; September 21, 2021. Accessed July 10. https://www.fda.gov/news-events/press-announcements/fda-authorizes-software-can-help-identify-prostate-cancer