On June 6, 2016 Kite Pharma, Inc. (Nasdaq:KITE) ("Kite") reported results to be presented at the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting from a study of low-dose chemotherapy conditioning followed by anti-CD19 chimeric antigen receptor (CAR) T-cell therapy (Press release, Kite Pharma, JUN 6, 2016, View Source [SID:1234513027]). The results showed that CAR T-cell therapy was effective in inducing a high response rate in patients with advanced non-Hodgkin lymphoma (NHL). The results will be presented today as a Late Breaking Abstract by James N. Kochenderfer, M.D., an investigator in the Experimental Transplantation and Immunology Branch of the National Cancer Institute (NCI) Center for Cancer Research (Hall D2, Time: 4:42PM CDT, Abstract #3010).

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In this study of 22 patients (19 diffuse large B-cell lymphoma, 2 follicular lymphoma, and 1 mantle cell lymphoma), objective responses were seen in 16 patients (73%). Twelve of 22 patients (55%) achieved complete responses following low-dose chemotherapy conditioning regimen. Kite is using a similar conditioning regimen in its ZUMA-1 Study of KTE-C19, an anti-CD19 CAR T cell therapy. Nine of 19 patients (47%) with diffuse large B-cell lymphoma (DLBCL) achieved complete responses, which are all ongoing with a duration of 7+ to 20+ months. Additionally, the three patients with mantle cell lymphoma and follicular lymphoma achieved complete responses. Reversible grade 3 or 4 neurotoxicity including confusion, dysphasia, encephalopathy, and gait disturbances was observed in 55% of treated patients.

"Patients with chemorefractory DLBCL have few effective treatment options," said Jeff Wiezorek, M.D., M.S., Kite’s Senior Vice President, Clinical Development. "These early results are encouraging and served as the foundation for Kite’s ongoing KTE-C19 ZUMA-1 Study."

According to the American Cancer Society, NHL is one of the most common cancers in the United States and DLBCL is the most common form of the disease accounting for one out of every three cases of NHL.1 It is estimated that approximately 26,000 people will be diagnosed with DLBCL in the United States in 2016. DLBCL is an aggressive and fast growing lymphoma, but considered curable in patients who respond to initial treatment with a chemotherapy-based regimen. Patients with chemorefractory DLBCL face limited treatment options and historically poor outcomes.

This study was performed pursuant to a Cooperative Research and Development Agreement (CRADA) between the NCI and Kite.

On June 6, 2016 Kite Pharma, Inc. (Nasdaq:KITE) ("Kite") reported updated durability of complete responses in the Phase 1 portion of the ZUMA-1 trial (Press release, Kite Pharma, JUN 6, 2016, View Source [SID:1234513026]). The study is evaluating KTE-C19 in patients with chemorefractory diffuse large B-cell lymphoma (DLBCL), an aggressive form of non-Hodgkin lymphoma (NHL). KTE-C19 is an investigational therapy in which a patient’s T-cells are genetically modified to express a chimeric antigen receptor (CAR) that is designed to target the antigen CD19, a protein expressed on the cell surface of B-cell lymphomas and leukemias. The results will be presented today at the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (abstract #7559).

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"Three reported complete remissions in patients with chemorefractory DLBCL after a single treatment with CAR T-cell therapy are still ongoing at nine months. This is remarkable given that single-digit complete response rates are historically observed in patients who do not respond to chemotherapy," said Sattva S. Neelapu, Associate Professor and Director of Translational Research, Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center. "These results are extremely important as CAR engineered T-cells have the potential to transform the treatment landscape for chemorefractory DLBCL."

The Phase 1 portion of ZUMA-1 treated a total of 7 patients with chemorefractory DLBCL. The results showed that treatment with KTE-C19 achieved rapid and durable responses in patients with chemorefractory disease (objective response rate 71%, complete response rate 57%). Ongoing complete responses were observed in 3 patients after nine months of follow-up. KTE-C19 related adverse events consisted predominantly of cytokine release syndrome (CRS) and neurotoxicity, which were generally reversible. Grade 3 or higher CRS was observed in 14% and neurotoxicity in 57%; all were reversible except in one patient with dose-limiting toxicity.

KTE-C19, currently in Phase 2 clinical studies, has received Breakthrough Therapy Designation and Orphan Drug status from the U.S. Food and Drug Administration for the treatment of patients with chemorefractory DLBCL, primary mediastinal B-cell lymphoma, and transformed follicular lymphoma. The European Medicines Agency has also granted KTE-C19 access to regulatory support under its Priority Medicines (PRIME) initiative for the treatment of DLBCL and Orphan Drug Designation for various hematological indications.

About Diffuse Large B-Cell Lymphoma

According to the American Cancer Society, NHL accounts for about four percent of all cancers in the United States, making it one of the most common cancers diagnosed. DLBCL is the most common form of the disease, accounting for one out of every three cases of NHL.1 It is estimated that 26,000 people will be diagnosed with DLBCL in the United States in 2016. DLBCL is an aggressive and fast growing lymphoma, but considered curable in patients who respond to initial treatment with a chemotherapy-based regimen. Patients with chemorefractory DLBCL face limited treatment options and historically poor outcomes.

About Kite’s ZUMA Clinical Programs for KTE-C19

KTE-C19 is an investigational therapy in which a patient’s T-cells are genetically modified to express a CAR that is designed to target the antigen CD19, a protein expressed on the cell surface of B-cell lymphomas and leukemias. Kite is currently enrolling four pivotal studies (also known as ZUMA studies) for KTE-C19 in patients with various B-cell malignancies.

Study Phase Indication Status
ZUMA-1
NCT02348216 Phase 2 Pivotal
(N=112)
Chemorefractory DLBCL, PMBCL, TFL
Phase 2 enrolling
ZUMA-2
NCT02601313 Phase 2 Pivotal
(N=70) Relapsed/refractory MCL Phase 2 enrolling
ZUMA-3
NCT02614066 Phase 1/2 Pivotal
(N=75) Relapsed/refractory Adult ALL Phase 1/2 enrolling
ZUMA-4
NCT02625480 Phase 1/2 Pivotal
(N=75) Relapsed/refractory Pediatric ALL Phase 1/2 enrolling

DLBCL = diffuse large B-cell lymphoma
PMBCL = primary mediastinal B-cell lymphoma
TFL = transformed follicular lymphoma
MCL = mantle cell lymphoma
ALL = acute lymphoblastic leukemia

On June 6, 2016 Heat Biologics, Inc. (Nasdaq:HTBX), an immuno-oncology company developing novel therapies that activate a patient’s immune system against cancer, reported that it presented a poster entitled "Broadening response rates to PD-1 therapy in advanced lung adenocarcinoma: Viagenpumatucel-L (HS-110) in combination with nivolumab in the ongoing DURGA trial" (Abstract #TPS9102) at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Heat Biologics, JUN 6, 2016, View Source [SID:1234513020]). The poster was accepted within the Trials in Progress category and as such, reviewed the design and endpoints for the ongoing Phase 1b study of HS-110 in combination with anti-PD-1 checkpoint inhibitor, nivolumab, for the treatment of non-small cell lung cancer (NSCLC). Eight patients are currently enrolled.

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Recent study findings, not presented at ASCO (Free ASCO Whitepaper), suggest that the addition of HS-110 to nivolumab does not significantly alter the nivolumab safety profile to-date. In addition, case studies of three trial patients (one non-responder and two responders) have been characterized. While all three patients showed a decrease in immune cell PD-1 expression, which is consistent with nivolumab’s mechanism of action, both responders also showed a decrease in immunosuppressor cells, as well as increases in activated effector T cells in the peripheral blood. Furthermore, the two responders showed an increase in CD8+ T cells in biopsy samples after treatment with the HS-110/nivolumab combination. ELISPOT analysis of patient blood samples demonstrated induction of antigen-specific immune responses to both total vaccine antigen and individual shared tumor antigens in both responding patients, but not the clinical non-responder. Finally, these responding patients also had low-grade injection site reactions in addition to rash, which the non-responder did not, suggesting their clinical and immune responses may be attributed to the HS-110 vaccine.

These data are included in the updated corporate presentation which is available on Heat’s corporate website at www.heatbio.com. As previously announced, full topline data on all eight patients is expected to be presented in the fourth quarter, including all primary and secondary endpoints.

"In these early data, we observed a correlation between patients’ clinical outcomes and their immunological responses, which we believe indicates that tumor response may be a result of increased immunological activity," said Melissa Price, Ph.D., Heat’s VP of Product Development. "Additionally, the two responders qualitatively converted from low to high tumor infiltrating lymphocytes (TILS), which is consistent with data previously reported from our bladder cancer study. This finding supports our hypothesis that patients with low levels of TILs, who typically do not respond well to single-agent checkpoint inhibitors, may respond to a combination with our ImPACT vaccine."

On June 06, 2016 Calithera Biosciences, Inc. (Nasdaq:CALA), a clinical stage biotechnology company focused on the development of novel cancer therapeutics, reported that clinical data from its lead product candidate CB-839, a first-in-class glutaminase inhibitor, was presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (ASCO) (Free ASCO Whitepaper), in Chicago, Illinois (Press release, Calithera Biosciences, JUN 6, 2016, View Source;p=RssLanding&cat=news&id=2175227 [SID:1234513016]). The data demonstrated the clinical activity, tolerability and unique mechanism of action of CB-839 in patients with renal cell carcinoma and triple negative breast cancer (TNBC).

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"CB-839 is the first tumor metabolism drug to target a pathway that starves cancer cells by directly depriving them of a key nutrient. The combination data presented at ASCO (Free ASCO Whitepaper) demonstrates that CB-839 can safely be added to standard of care therapeutics to treat solid tumors with the potential to improve clinical outcomes," said Susan Molineaux, PhD, President and Chief Executive Officer of Calithera.

CB-839 in Renal Cell Carcinoma

Dr. Funda Meric-Bernstam from MD Anderson Cancer Center will present a poster titled, "Phase I study of CB-839, a small molecule inhibitor of glutaminase, alone and in combination with everolimus in patients with renal cell carcinoma," (Abstract #4568). As of May 23, 2016, thirty-five renal cell carcinoma patients had been treated, including ten in combination with 10 mg daily everolimus, and twenty-five patients treated with CB-839 dosed as a monotherapy. In the combination group, the overall disease control rate was 80%, including one partial response; among eight clear cell and papillary patients, the disease control rate was 100%. The median time on study for these patients is currently 6.5+ months, exceeding the expected progression free survival of everolimus alone in this population. Time on treatment is currently equal to, or greater than the time on prior therapy for most patients, and seven of eight patients remain on study. The combination of CB-839 and everolimus has been well tolerated to date. There was one case of dose-limiting, grade 3 pruitic rash at the 400 mg dose level, which led to a reduction in the dose of everolimus for that patient. On the basis of this efficacy data, the company plans to continue development in combination therapy for renal cell carcinoma.

Among 21 efficacy evaluable patients treated as a monotherapy, 52% experienced stable disease or better, including one partial response. The monotherapy cohort represents an update from the data presented November 8, 2015 at the American Association of Cancer Research-NCI-EORTC conference.

CB-839 in Triple Negative Breast Cancer

Dr. Angela DeMichele from the University of Pennsylvania presented a poster titled, "Phase I study of CB-839, a small molecule inhibitor of glutaminase in combination with paclitaxel in patients with triple negative breast cancer," (Abstract #1011). The abstract was also selected for a poster discussion presentation on Sunday, June 5, 2016. Eligible patients include locally advanced/metastatic TNBC, refractory disease, with prior paclitaxel allowed. As of May 23, 2016, fifteen triple negative breast cancer patients had been treated with doses of CB-839 of 400, 600 or 800 mg bid in combination with 80 mg/m2 IV paclitaxel, weekly, three weeks out of four. The majority of patients had received at least three prior lines of therapy. Six patients received five or more prior therapies in the advanced/metastatic setting. Most patients had received prior taxanes in either the neo-adjuvant (n=7) or metastatic (n=5) setting. Among patients treated with CB-839 doses of at least 600 mg bid (n=8), there were 3 partial responses (38%) and disease control (response or stable disease) in 7 patients (88%). Two of the partial responses were observed in patients that were refractory to paclitaxel in a prior course of therapy. The combination of CB-839 and paclitaxel has been well tolerated to date, with adverse events that have been easily manageable and reversible, including several paclitaxel related toxicities. There was one case of dose-limiting, recurrent grade 3 neutropenia at the 400 mg dose level, which led to a reduction in the dose of paclitaxel for that patient.

Investor Event and Webcast

Calithera will host a conference call and webcast on Monday June 6, 2016, at 6:30 p.m. CT to review the clinical data presented at ASCO (Free ASCO Whitepaper) from the ongoing Phase I study of CB-839. The live audio webcast can be accessed via the Investor section of the Company’s website at www.calithera.com. The conference call can be accessed by dialing (855) 783-2599 (domestic) or (631) 485-4877 (international) and refer to conference ID 23768811. Please log in approximately 5-10 minutes before the event to ensure a timely connection. The archived webcast will remain available for 30 days following the call.