City of Hope has entered into a licensing agreement with the immuno-oncology company Imugene Ltd. for the patents covering a combination immunotherapy that enables CD19-directed CAR T-cell therapies to target and eradicate solid tumors that are difficult to treat with CAR T-cell therapy alone.

The novel immunotherapy combination is comprised of a CD19-expressing oncolytic virus developed at City of Hope and a CD19-directed CAR T-cell therapy, which was examined in preclinical research recently published in 

In this research, investigators examined the ability of the genetically-engineered oncolytic virus to enter tumor cells and force the expression of the CD19 protein on the cell surface.

 Investigators hope this new research will expand the utility of CD19-targeted CAR T-cell therapy, a modality that is currently FDA approved for use in patients with certain hematologic malignancies, to those with solid tumors.

“Our research demonstrates that oncolytic viruses are a powerful and promising approach that can be combined strategically with CAR T-cell therapy to effectively target solid tumors in patients,” Saul Priceman, PhD, senior study author and an assistant professor in the Department of Hematology & Hematopoietic Cell Transplantation at City of Hope, stated in a press release. “This therapeutic platform addresses 2 major challenges that make solid tumors so difficult to treat with immunotherapy. There are limited solid tumor targets that T cells can be redirected against with CARs. Solid tumors are surrounded by a brick wall—a so-called immunosuppressive tumor microenvironment. When a CAR T cell attempts to enter the tumor, survive, and kill cancer cells, it can’t effectively because of this barrier.”

Through the licensing agreement, Imugene Ltd. will acquire, further develop, and commercialize the cell therapy technology, which includes CF33-CD19, (onCARlytics

), a drug that tags cancer cells for CAR T-cell elimination.

The oncolytic virus was first designed at City of Hope to infiltrate tumor cells and produce truncated CD19; this was successfully demonstrated in several cell lines, including triple-negative breast cancer, prostate cancer, ovarian cancer, head and neck cancer, and brain tumors. Then, CD19-targeted CAR T cells and the CD19-expressing oncolytic virus were combined in vitro to be evaluated in mouse models.

Results from the studies showed that truncated CD19 was expressed by tumor cells more quickly than the virus was able to eradicate it; this provided investigators with the opportunity to target this marker with CD19-directed CAR T-cell therapy. Moreover, results showed that the mice that were cured of their cancer with the combination experienced prolonged protective antitumor immunity.

“When we infected tumor cells with the virus, we observed the first signal that this may work. CD19t was being expressed by tumor cells much sooner than the virus was able to kill them, giving us a window of opportunity to be targeted by CD19-CAR T cells,” Anthony Park, PhD, study investigator and a postdoctoral fellow at City of Hope, stated in the press release. “The combination of the 2 had a powerful, synergistic effect. The immune system built a memory response to the tumor. Once it eradicated tumors, following the initial combination treatment, the mice were shielded against tumor recurrences.”

Investigators hope to launch a phase 1 clinical trial further examining this approach in 2022.

Imugene licenses CD19 oncolytic virus from City of Hope to turn Car T Therapy against solid tumors. News release. City of Hope. May 18, 2021. Accessed May 24, 2021. 

City of Hope scientists use two powerful immunotherapies to eradicate solid tumors. News release. City of Hope. September 2, 2020. Accessed May 24, 2021. 

Park AK, Fong Y, Kim S-I, et al. Effective combination immunotherapy using oncolytic viruses to deliver CAR targets to solid tumors. 

. 2020;12(559):eeaz1863. doi:10.1126/scitranslmed.aaz1863

Articles

City of Hope has entered into a licensing agreement with Imugene Ltd. for the patents covering a combination immunotherapy that enables CD19-directed CAR T-cell therapies to target and eradicate difficult-to-treat solid tumors.

Oncolytic Virus/CAR T-Cell Therapy Combo Shows Preclinical Potential in Solid Tumors  

Kaiku Health has announced that they are partnering with the global healthcare company Novartis to develop a digital patient monitoring and management system specifically for patients with melanoma who are receiving BRAF/MEK combination therapies.

“Kaiku Health is a digital application that guides cancer patients through treatment and recovery. The application interviews the patient along the care journey. Then, based on patient reporting and feedback, it provides personalized feedback, information, and education for the patient. At the same time, the data is securely transmitted to the patient’s care team and Kaiku provides them with their own dashboard, “explained Lauri Sippola, the chief executive officer of Kaiku in an interview with 

. “In this collaboration we have announced with Novartis, we are creating a specific patient module to support [patients with] melanoma who will receive BRAF/MEK combination therapies. We are cocreating personalized support and targeted algorithms for supporting patients and the care team to achieve optimal therapy of each patient.”

Founded in Finland in 2012, Kaiku Health’s platform is utilized in clinical routine use in over 40 cancer clinics and hospitals in Europe.

The new module from Kaiku and Novartis will utilize machine learning to optimally personalize care and symptom management information for each patient. It is designed to track symptoms and relay them, along with additional information, to the patient’s care team. The collaboration also aims to generate novel insights into patient outcomes in a real-world setting and to continue to advance the machine learning–based algorithms to improve the quality of life (QoL) of patients.

“We believe that digital monitoring will improve patient experience, toxicity management, and symptom management,” Sippola said. “Ultimately, we hope this will lead to improved outcomes for patients. By utilizing predictive, machine learning–based models, we believe the care will be more personalized and more predictive. By using prediction, we can support patients before some symptoms or potential adverse effects might happen. Our ultimate mission is to improve the QoL of [patients with] cancer.”

The module is planned to be piloted at cancer centers in the Netherlands, Germany, Switzerland, and Italy beginning in May 2021; it will be available as a mobile application or a web browser–based application accessible via desktop computer.

“With the current situation of the world and the COVID-19 pandemic, it is accelerating the need for digital applications that support remote patient monitoring,” Sippola concluded. “We are seeing a growing number of cancer centers adopting digital patient monitoring. Patients are really expecting digital solutions that will support their care. It’s a very exciting time to work and develop solutions with global partners like Novartis and Elekta.”

Kaiku Health to develop digital patient monitoring for melanoma with leading global medicines company. News Release. Kaiku Health. April 20, 2021. Accessed May 20, 2021. https://kaikuhealth.com/press/kaiku-health-to-develop-digital-patient-monitoring-for-melanoma-with-leading-global-medicines-company/

Kaiku Health and Novartis Collaborate on Specialized Digital Patient Monitoring Technology

Daiichi Sankyo Inc. is collaborating with Guardant Health Inc. to develop a companion diagnostic for fam-trastuzumab deruxtecan-nxki (Enhertu), which is being studied to treat patients with advanced metastatic 

-mutated non‒small cell lung cancer (NSCLC).

“Lung cancer is an area where we have more and more specific therapies so identifying patients selectively for a specific therapy becomes more and more important,” said Gilles Gallant, BPharm, PhD, FOPQ, senior vice president, global head in oncology development, oncology R&D, at Daiichi Sankyo, told 

. “At diagnosis, a tumor biopsy is done, but for second-line treatment, there are risks for the patient in taking a biopsy. But we have to make sure patients have the mutation. This is extremely important for the drug to work.”

A blood-based assay would be faster, simpler, and less invasive for the patient, Gallant added. “Now, we need to demonstrate that those assays are good, if not better, than taking a piece of the tumor.”

Trastuzumab deruxtecan is currently being studied as a second-line treatment for patients with 

-mutated metastatic NSCLC after at least 1 regimen of prior anticancer therapy that must have contained a platinum-based chemotherapy drug.

Patients in the global phase 2 DESTINY-Lung02 trial (NCT04644237) will be randomized in a 2:1 ratio to receive either the 5.4 mg/kg or 6.4 mg/kg dose of trastuzumab deruxtecan. The primary end point of the study is objective response rate (ORR), as assessed by blinded independent central review (ICR). Secondary end points include disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), investigator-assessed ORR, overall survival (OS), pharmacokinetics, time to response, quality of life, and safety.

Trastuzumab deruxtecan has been approved by the FDA to treat patients with 

locally advanced or metastatic HER2-positve gastric or gastroesophageal junction adenocarcinoma

 who had previously received a trastuzumab (Herceptin)-based regimen.

Investigators presented an interim analysis from the phase 2 DESTINY-Lung01 trial (NCT03505710) at the 2020 ASCO Virtual Scientific Program. Data were presented from 42 patients with 

-mutant unresectable and/or metastatic nonsquamous NSCLC.

The primary end point of confirmed ORR, which was assessed by ICR, was 61.9% (95% CI, 45.6%-76.4%) with trastuzumab deruxtecan monotherapy (6.4 mg/kg). Patients who received the antibody-drug conjugate achieved a DCR of 90.5% (95% CI, 77.4%-97.3%), with a median PFS of 14.0 months (95% CI, 6.4-14.0). The median DOR and OS had not yet been reached at the time of data cutoff.

The DESTINY-Lung01 trial used data from tissue testing to confirm 

 mutation status, Gallant said. “However, we wanted a much easier test to identify those patients. A blood test opens up an easier way to identify potential patients for this agent.”

Guardant360 CDx is an FDA-approved liquid biopsy that provides comprehensive genomic profiling results to guide treatment in all solid tumors. “It is approved for 55 genes for tumor profiling, which gives the physician a broad view of each patient to use in therapy selection,” Justin Odegaard, MD, PhD, vice president of clinical development at Guardant Health, told 

“A companion diagnostic indication for FDA is built around 2 basic things. First, is the test accurate and analytically correct?” Odegaard questioned. “And second, do patients identified by the test respond to the drug?” Odegaard further added that the goal for this specific companion diagnostic approval is to improve overall patient access to optimal therapy. “We are working to help physicians determine who is eligible to receive trastuzumab deruxtecan,” Odegaard noted.

Guardant360 CDx is also an approved companion diagnostic for osimertinib (Tagrisso) to identify patients with NSCLC who have tumors that harbor 

The test is also being pursued as a companion diagnostic for other therapies to treat patients with NSCLC. Amgen and Guardant Health are collaborating to develop a test for sotorasib for patients with NSCLC who have the 

The FDA is currently reviewing a new drug application for sotorasib

 for this indication under its Real-Time Oncology Review (RTOR) pilot program. The application has a received a priority review designation.

Janssen Biotech and Guardant worked together to develop a companion diagnostic for 

, an investigational EGFR/MET bispecific antibody that has recently received FDA approval for use in adult patients with NSCLC who harbor 

regulatory agency gave the green light to Guardant360 CDx

 to determine which patients may derive benefit from amivantamab after progressing on, or after platinum-based chemotherapy.

Guardant Health announces collaboration with Daiichi Sankyo to develop Guardant360 CDx as a companion diagnostic for Enhertu in advanced metastatic non‒small cell lung cancer. News release. Guardant Health. April 27, 2021. Accessed May 25, 2021. 

DESTINY-Lung02 phase 2 trial of Enhertu initiated in patients with HER2 mutated non‒small cell lung cancer. News release. Daiichi Sankyo. March 29, 2021. Accessed May 25, 2021. 

Enhertu. Prescribing information. Daiichi Sankyo; 2021. Accessed May 18, 2021. 

Smit EF, Nakagawa K, Nagasaka M, et al. Trastuzumab deruxtecan (T-DXd; DS-8201) in patients with HER2-mutated metastatic non–small cell lung cancer (NSCLC): interim results of DESTINY-Lung01. 

. 2020;38(suppl 15):9504. doi:10.1200/JCO.2020.38.15_suppl.9504

Guardant Health announces collaboration with Amgen to develop a global liquid biopsy companion diagnostic for AMG 510 KRAS G12C inhibitor. News release. Guardant Health. January 13, 2020. Accessed May 25, 2021. 

FDA grants sotorasib priority review designation for the treatment of patients with KRAS G12C mutated locally advanced or metastatic non‒small cell lung cancer. News release. Amgen. February 16, 2021. Accessed May 25, 2021. 

Guardant Health announces collaboration with Janssen to develop liquid biopsy companion diagnostic. News release. Guardant Health. July 8, 2020. Accessed May 18, 2021. 

Guardant360 CDx receives FDA approval as companion diagnostic for Janssen’s RYBREVANT (amivantamab-vmjw) for use in patients with advanced non-small cell lung cancer with EGFR exon 20 insertion mutations. News release. May 21, 2021. Accessed May 25, 2021. 

Daiichi Sankyo Inc. is collaborating with Guardant Health Inc. to develop a companion diagnostic for fam-trastuzumab deruxtecan-nxki, which is being studied to treat patients with advanced metastatic HER2-mutated non‒small cell lung cancer.

Pipeline Report: May 2021

Articles

Oncolytic Virus/CAR T-Cell Therapy Combo Shows Preclinical Potential in Solid Tumors

Kaiku Health and Novartis Collaborate on Specialized Digital Patient Monitoring Technology