JTCC and Georgetown’s Alliance in Cancer Research Achieves New Level With Immunotherapy Breakthrough

It was 5:00 PM on a Monday, and Andrew Pecora, MD, FACP, CPE, was just wrapping up his practice for the day when one of his nurses came to the door, asking if he could see one more patient.

“‘This is a 19-year-old that they just rolled in, and he’s on a stretcher’,” Pecora recounted the nurse telling him in May 2019. “‘He’s in the room crying with his family.”

He walked in to see a patient with stage 4 epithelioid sarcoma, along with a large soft tissue back mass that was leading into his spine. Pecora, division chief of skin cancer and sarcoma services at John Theurer Cancer Center (JTCC), Hackensack Meridian Health, estimated that he was weeks away from dying. 

The patient had an ECOG performance status of 4 with rapidly progressing bulky disease, and had progressed on tazemetostat (Tazverik), pazopanib (Votrient), surgery, chemotherapy with doxorubicin and ifosfamide, and involved field radiation.¹

The standard choice for this patient, he said, would be hospice, “but not many parents want to hear that when it’s their 19-year-old on the stretcher.” 

Pecora knew that there were some early data with checkpoint inhibitors in sarcoma, but because the patient had epithelioid sarcoma, a rarer subtype, the information was even more limited. Relapsed/refractory epithelioid sarcoma in particular has a poor expected survival. 

In came Jeffrey Toretsky, MD, a professor of oncology and pediatrics at Georgetown Lombardi Comprehensive Cancer Center with a focus on sarcoma biology. Through numerous conversations with him and leaders from Dana-Farber Cancer Institute, it became obvious to Pecora and colleagues that checkpoint inhibitors could be effective in this case, especially once it was identified that the tumor had SMARCB1 inactivation.

As part of a compassionate use authorization, the combination of nivolumab (Opdivo) and ipilimumab (Yervoy) was administered to the patient, and within 2 weeks had responded to treatment followed by a PET-negative complete remission. Once a second negative PET/CT scan occurred, the combination therapy was discontinued. 

“This all happened that night—people stayed until like 10 PM,” said Pecora, adding that the patient was admitted to the hospital shortly after receiving immunotherapy. “His immune system turned on and started killing his cancer. Within 3 weeks, [the mass] on his back almost evaporated. It was a miracle; his disease completely went away.” 

Collaboration Adds Value

The collaboration to save this young patient, who achieved a complete response by October 2019, is a byproduct of the Georgetown Lombardi Comprehensive Cancer Center Consortium, of which JTCC and Georgetown are both part of. Georgetown was formally recognized as a National Comprehensive Cancer Center research consortium in 2019.

It had been an ambition of JTCC to be part of a National Cancer Institute (NCI)–designated comprehensive cancer center, and it was in Georgetown’s interest to expand its footprint, especially in acute leukemias and multiple myeloma, Pecora added.

The first step was putting a bone marrow transplant program back at Georgetown, “and with the success of that program, that gave us the confidence to work closer together,” he reflected. 

Pecora worked in tandem with Louis M. Weiner, MD, director of Georgetown Lombardi Comprehensive Cancer Center and the MedStar Georgetown Cancer Institute, to bring the 2 organizations together before applying to become a designated consortium. 

 “We’re one of the largest providers of cancer services, and we have always been a major contributor to advances in this field,” said Pecora. “But we wanted to go to the next level and become a recognized entity—both on translational science as well as clinical science. The way to do that was to be become part of an NCI-designated cancer center.”

The joint efforts feature work on phase 1 and beyond studies of novel cancer therapies. Both institutions also evaluate new technologies, as well as develop and launch research that will provide a greater understanding of the ways in which northern New Jersey and Washington D.C. populations are impacted by cancer.²

Michael B. Atkins, MD, deputy director of the Georgetown Lombardi Comprehensive Cancer Center and the Scholl Professor and vice chair of the Department of Medical Oncology at Georgetown University Medical Center, said the Consortium has also led to their institution having strong multiple myeloma and transplant programs, a growing leukemia program, and has allowed them to get involved in chimeric antigen receptor (CAR) T-cell therapy for patients with hematologic malignancies.

“That is something that will grow in the future to probably a broader cellular therapy service, [one] that involves the treatment of not only hematologic malignancies with cellular therapy, but solid tumors using tumor-infiltrating lymphocyte [TILs] protocols that will hopefully soon be commercially available,” said Atkins. 

Both campuses have merged their clinical research efforts across various diseases, expanded their investigator-initiated clinical trials, and Atkins added, have expanded their bedside to bench reverse translational research protocols.

Moreover, Atkins cited Georgetown’s robust population science program as another way to collaborate with JTCC, which focuses on issues from cancer detection to cancer policy. 

“Our Cancer Prevention and Control Program has been heavily focused on addressing the needs within our patient catchment area of Washington D.C., which has some of the highest rates of cancer of any region within the United States,” Atkins said. “Those are unique needs that are focused more on a particular set of minority communities. Although the population in New Jersey is different, we have begun the work of identifying their needs and establishing a framework for addressing them.”

Georgetown leaders are now working to set up a satellite, population science–focused effort within JTCC to address the needs of the geographical area, which, he said, is a population of more Hispanic individuals, heavy smoking history, and various cancer types.

But one of the larger mergers between the 2 groups comes from the experience with immunotherapy. Between JTCC’s robust cellular therapy efforts with CAR T-cell therapy in hematologic cancers, and Georgetown’s interest in expanding immunotherapy, the two groups felt they could combine their expertise to build one of the leading immunotherapy efforts on the East coast. 

“We will be able to not only provide standard of care, cellular therapies, but we’ll also be able to participate in industry-sponsored cellular therapy research of all different types, and develop our own investigator-initiated cellular therapy trials,” Atkins envisioned. 

Research Continues

Regularly, the 2 institutions interact through their 8 respective disease groups with monthly conference calls to review research portfolios, share updates with patients on studies, and discuss ideas for future clinical trials. While such conversations previously took place on traditional phone calls, the format turned virtual via Zoom and WebEx once the coronavirus disease 2019 pandemic hit.

“We also use those calls to discuss clinical cases that are potentially problematic and how we would best manage those patients,” Atkins explained. “Those calls function as virtual tumor boards to discuss what happened in a particular case that might help us better understand the biology of that particular disease and its response to a specific therapy, and to potentially use that information to design a clinical trial to address our working hypothesis.”

Bi-weekly discussions also take place with leaders of disease groups and cancer research programs to review institutional-only challenges and identify solutions, issues in melding clinical research efforts, and to present on investigator-initiated trials that could add correlative science.

“We're doing lots of research efforts across the whole array of cancer, everything from prevention, early detection, to treatment of all forms of cancer,” Pecora said. “The Consortium is involved in a number of clinical trials together; we are truly working together to stamp out cancer. The fact that we have a reach from northern New Jersey down to Washington is one of the most densely populated parts of the country so we can influence you know, tens of millions of Americans.”

Case in Point

During the 2019 Connective Tissue Oncology Society (CTOS) Annual Meeting in Tokyo, Japan, where Pecora and Toretsky were in attendance and talking science with other colleagues, they came to figure out why checkpoint inhibitors were effective in this patient—and the paper was published in the Journal of Immunotherapy, of which Pecora is the lead author of. 

Because the patient’s tumor was INI1-deficient, it also had extensive cytotoxic T-cell infiltration, which is known to be a predictor of response to immunotherapy.^3-5 

For Atkins, who has been involved with immunotherapy for more than 3 decades and has been a key player in the development of nivolumab and ipilimumab in renal cell carcinoma and melanoma, it was gratifying to see the combination have an effect in epithelioid sarcoma. 

“We need to keep doing research to identify more tumors, and more biomarkers, that identify which subset of patients with different tumors use these checkpoints to escape the immune response,” he said.

In the Journal of Immunotherapy paper, the investigators concluded that combination immunotherapy warrants further exploration for patients with INI1-deficient sarcomas in the salvage setting, regardless of prior treatment, level of tumor mutational burden, and microsatellite instability status. Extent of disease and performance status may also be characteristics to disregard when deciding to give checkpoint inhibition to a patient with sarcoma.

Andre Goy, MD, MS, physician-in-chief of the Hackensack Meridian Health Oncology Care Transformation Service, and chairman and executive director of JTCC, Lydia Pfund chair for Lymphoma, chief of the Division of Lymphoma, professor of medicine at Georgetown University, said the Consortium showcases the importance of pushing the envelope to find actionable items even, and in particularly, in difficult situations.

“It highlights the power of fantastic outcomes when you find the Achillean heel of a given tumor, and fantastic power of the immune system as durable therapy,” Goy added. 

As of the 19-year-old’s last visit in June 2020, he had resumed normal activities. His sarcoma was asymptomatic.

“Now, there’s a whole new bridge—literally a breakthrough treatment—and a disease that otherwise was 100% fatal in a young person. It’s an amazing story,” Pecora concluded. “Had we not been part of the Consortium, I wouldn’t have known Dr. Turetsky, we wouldn’t have had those conversations, and we may not have treated this man this way. And, we clearly would not have been able to publish it with the underlying science elucidated. That’s the power of the Consortium.”

References

1. Pecora A, Halpern S, Weber M, et al. Rapid and complete response to combination anti-CTLA-4 and anti-PD-1 checkpoint inhibitor therapy in a patient with stage IV refractory end-stage epithelioid sarcoma: a case report. J Immunother. 2020;43(9):286-290. doi:10.1097/CJI.0000000000000332
2. Our Research Collaborations. Georgetown Lombardi Comprehensive Cancer Center. https://bit.ly/3jDPI5l
3. Leruste A, Tosello J, Ramos R, et al. Clonally expanded T cells reveal immunogenicity of rhabdoid tumors. Cancer Cell. 2019;36(6):1-16. doi:10.1016/j.ccell.2019.10.008
4. Chun HJ, Johann P, Milne K, et al. Identification and analyses of extra-cranial and cranial rhabdoid tumor molecular subgroups reveal tumors with cytotoxic T cell infiltration. Cell Rep. 2019;29:2338–2354. doi:10.1016/j.celrep.2019.10.013
5. Geoerger B, Karski EE, Zwaan M, et al. A phase I/II study of atezolizumab in pediatric and young adult patients with refractory/relapsed solid tumors (iMATRIX-atezolizumab). J Clin Oncol. 2017;35(suppl_15):10524. doi:10.1200/JCO.2017.35.15_suppl.10524