Kura Oncology Reports Overall Survival Data from Phase 2 Trial of Tipifarnib in HRAS Mutant Head and Neck Squamous Cell Carcinoma

On May 29, 2020 Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, reported updated clinical outcome data from its RUN-HN study, a Phase 2 open-label, single-arm trial of tipifarnib in patients with HRAS mutant head and neck squamous cell carcinoma (HNSCC) whose disease had progressed after prior therapy (Press release, Kura Oncology, MAY 29, 2020, View Source [SID1234558699]). These data are being presented in an oral session at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Virtual Scientific Program, being held May 29-31, 2020. A copy of the presentation is available on Kura’s website at www.kuraoncology.com/pipeline/publications.

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At data cutoff, 21 patients with HRAS mutant HNSCC were enrolled1, of whom 18 were evaluable for efficacy. Nine of the 18 evaluable patients achieved a confirmed partial response (PR), for an objective response rate (ORR) of 50% (95% CI, 26.0 to 74.0), with a median duration of response of 14.7 months. Median progression-free survival (PFS) was 5.9 months (95% CI, 3.5 to 19.2), compared to 2.8 months on the patients’ last prior therapy. Median overall survival (OS) was 15.4 months (95% CI, 7.0 to 46.4). Patients had a median of two prior lines of therapy (range 0-6). Robust activity was seen despite resistance to chemotherapy, immunotherapy and/or cetuximab.

ORR for three FDA-approved therapies for treatment of HNSCC in the second line range from 13-16%, with median PFS of 2-3 months and median OS of 5-8 months.

"It’s encouraging to see robust overall survival data for tipifarnib, which demonstrate a potentially meaningful development for HNSCC patients with HRAS mutations in the advanced setting," said Alan Ho, M.D., Ph.D., of Memorial Sloan Kettering Cancer Center and principal investigator of the study. "These data add to the body of evidence emerging for tipifarnib in second line HNSCC patients, a patient population with very few treatment options and a high unmet need. These results also highlight the importance of tumor genomic profiling to identify patients with HRAS mutations who could potentially be suitable for tipifarnib treatment."

Patients in the RUN-HN trial received tipifarnib at a starting dose of 600 or 900 mg orally twice daily on days 1-7 and 15-21 of 28-day cycles. Tipifarnib was generally well-tolerated. The most common grade 3 or 4 adverse events (AEs) seen in at least 10% of patients were cytopenias and GI disturbances.

"We believe a median overall survival of 15 months is unprecedented in this patient population and represents a substantial improvement compared to historical benchmarks with current standard of care," said Troy Wilson, Ph.D., J.D., President and Chief Executive Officer of Kura Oncology. "Taken together, these data support our enhanced focus on patients with HRAS mutant HNSCC, a population in desperate need of effective new treatments, and reinforce our confidence in the ongoing AIM-HN registration-directed trial."

The AIM-HN registration-directed trial of tipifarnib in patients with recurrent or metastatic HRAS mutant HNSCC is currently recruiting at approximately 90 clinical sites in the U.S., Europe and Asia. Patients interested in participating in this trial may talk to their doctor to have their tumor tested for the HRAS mutation for eligibility to enroll in this trial. Further details regarding the trial are available at clinicaltrials.gov (NCT03719690).

Activity in HRAS Mutant Salivary Gland Cancer and Urothelial Carcinoma

In addition to updated clinical outcome data in patients with HRAS mutant HNSCC, Kura also reported compelling single-agent activity in tumors of the salivary gland and urothelial carcinoma with HRAS mutations.

Seven recurrent/metastatic salivary gland cancer patients were enrolled in the all "other" HRAS mutant squamous cell carcinoma cohort in the Phase 2 tipifarnib trial and six additional patients were treated off-protocol through an expanded access program, of whom a total of 12 were evaluable for efficacy. One patient achieved a confirmed PR and seven achieved disease stabilization. Median PFS was 7.0 months (95% CI, 5.9 to 10.1) and median OS was 18.0 months (95% CI, 9.6 to 22.4). Adverse events observed were consistent with the known safety profile of tipifarnib. Salivary gland cancer is a rare disease for which standard treatments do not exist. Sequencing efforts in salivary gland cancers have identified HRAS mutations in up to 20% of high-grade histologic subtypes2,3.

In addition, 21 patients with metastatic urothelial carcinoma were treated in an investigator-sponsored trial conducted at the Samsung Medical Center in Seoul, South Korea, including 14 patients with HRAS missense mutations, one patient with an HRAS nonsense mutation and six patients with a polymorphism in the STK11 gene. A confirmed ORR of 24% (95% CI, 6 to 42) was achieved, with all five responses seen in patients with HRAS mutations. Median PFS was 4.7 months (95% CI, 2.5 to 5.6) and median OS was 6.1 months (95% CI, 5.0 to 7.2). The most frequently observed AEs in the study were consistent with the known safety profile of tipifarnib. Approximately 6% of urothelial carcinoma patients are estimated to carry an HRAS mutation4.

Disclosures

Memorial Sloan Kettering (MSK) has institutional financial interests related to the research in this release in the form of intellectual property rights and associated interests by virtue of licensing agreements between MSK and Kura.

About HNSCC

Head and neck squamous cell carcinoma (HNSCC) accounts for more than 885,000 new cancer cases each year worldwide with many cancers arising due to tobacco and/or alcohol use or human papilloma virus (HPV) infection. Despite advances in immunotherapy, the prognosis for advanced HNSCC patients remains poor with an estimated median overall survival (OS) of 13-15 months in patients when stratified by PD-L1 expression. Although the anti-epidermal growth factor (EGFR) antibody, cetuximab, was approved more than a decade ago, development of biomarker-directed therapies in HNSCC has been stymied by the limited number of druggable targets in the genomic landscape and the challenge of managing drug refractory recurrent/metastatic HNSCC.

About Tipifarnib

Tipifarnib, is a potent, selective and orally bioavailable inhibitor of farnesyl transferase in-licensed from Janssen in December 2014. Previously, tipifarnib was studied in more than 5,000 cancer patients and showed compelling and durable anti-cancer activity in certain patient subsets; however, no molecular mechanism of action had been determined that could explain its clinical activity across a range of solid tumor and hematologic indications. Leveraging advances in next generation sequencing as well as emerging information about cancer genetics and tumor biology, the Company is seeking to identify those patients most likely to benefit from tipifarnib. Tipifarnib has been granted Fast Track designation by the U.S. Food and Drug Administration for the treatment of patients with HRAS mutant HNSCC. Kura has received multiple issued patents for tipifarnib, providing patent exclusivity in the U.S. and foreign countries.

Allogene Therapeutics, with Collaborator Servier, Reports Positive Results from its Phase 1 ALPHA Study of ALLO-501 in Relapsed/Refractory Non-Hodgkin Lymphoma at the American Society of Clinical Oncology Annual Meeting

On May 29, 2020 Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T) therapies for cancer, in collaboration with development partner Servier, an independent international pharmaceutical company, reported positive initial results from Allogene’s dose escalation Phase 1 ALPHA study of ALLO-501 in relapsed/refractory non-Hodgkin lymphoma (NHL) (Press release, Allogene, MAY 29, 2020, View Source [SID1234558697]). Data were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting. This study utilizes ALLO-647, Allogene’s anti-CD52 monoclonal antibody (mAb), as a part of its differentiated lymphodepletion regimen.

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"We are very pleased with these initial Phase 1 results, which indicated that ALLO-501 and ALLO-647 were well tolerated and produced complete responses in patients with advanced NHL," said David Chang, M.D., Ph.D., President, Chief Executive Officer and Co-Founder of Allogene. "Based on these results, we believe we are on the right trajectory to make AlloCAR T therapy a reality for patients."

"Allogeneic CAR T therapies provide an off-the-shelf option that may make cellular therapies available to more patients," said Sattva S. Neelapu, M.D., Professor, Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center in Houston, Texas. "While longer follow-up is required, the response to ALLO-501 appears promising with 75% of patients remaining in response. Together with the positive safety profile, these data suggest that ALLO-501 has the potential to be an effective option if confirmed in future studies."

As of the May 2020 data cutoff, 23 patients were enrolled and 22 patients received ALLO-501. One patient was removed from the study prior to lymphodepletion due to acute renal failure from urinary obstruction. The median time from enrollment to the start of therapy was five days.

For the efficacy analysis, 19 out of 22 patients reached at least one month assessment as of the May 2020 data cutoff. Responses were observed across all cell doses and tumor histologies (diffuse large B-cell lymphoma and follicular lymphoma) with an overall response rate (ORR) of 63% and complete response (CR) rate of 37%. Higher dose ALLO-647 was associated with a higher CR rate of 50%, deeper lymphodepletion and delayed host T cell recovery. With a median follow-up of 3.8 months, nine of the 12 responding patients (75%) remain in response as of the data cutoff.

Cell Dose
and LD
regimen 39mg ALLO-647 90mg ALLO-647 All Patients
(N=19)
(95% CI)
40 x 106
CAR+ cells
(N=4) 120 x 106
CAR+ cells
(N=4) 360 x 106
CAR+ cells
(N=3) All 39mg
ALLO-647
(N=11) 120 x 106
CAR+ cells
(N=6) 360 x 106
CAR+ cells
(N=2) All 90mg
ALLO-647
(N=8)
ORR, n (%) 3 (75%) 3 (75%) 1 (33%) 7 (64%) 4 (67%) 1(50%) 5 (63%) 12/19 (63%)
(38%, 84%)
CR, n (%) 1 (25%) 1 (25%) 1 (33%) 3 (27%) 4 (67%) 0 (0%) 4 (50%) 7/19 (37%)
(16%, 62%)
One of the ongoing responders is a patient with an initial partial response (PR) who progressed by month two. This patient achieved a CR after re-treatment with the same dose of ALLO-501 and higher dose (90mg) ALLO-647. This patient is reflected as a PR in the table above and not as a CR.

Included in the overall efficacy analysis are three patients who were refractory to prior autologous CAR T therapy (the best response of progressive disease or disease progression within three months). These patients were also refractory to AlloCAR T therapy. In CAR T naïve patients, the ORR was 75% and the CR rate was 44%.

All Cell Doses +
39mg ALLO-647
(N=10) 120 x 106 and 360 x 106 CAR+ cells +
90mg ALLO-647
(N=6) All CAR T Naïve Patients
(N=16)
ORR, n (%) 7 (70%) 5 (83%) 12/16 (75%)
(48%, 93%)
CR, n (%) 3 (30%) 4 (67%) 7/16 (44%)
(20%, 70%)
No dose limiting toxicities, graft-vs-host disease, or Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) was observed.

Adverse Events of Interest Grade 1
N (%) Grade 2
N (%) Grade 3
N (%) Grade 4
N (%) Grade 5
N (%)
Cytokine Release Syndrome 2 (9%) 4 (18%) 1 (5%) - -
ICANS - - - - -
Graft-versus-Host Disease - - - - -
Infection 5 (23%) 4 (18%) 2 (9%) - -
Infusion Reaction 1 (5%) 9 (41%) 1 (5%) - -
Neutropenia - 1 (5%) 7 (32%) 7 (32%) -
Cytokine release syndrome occurred in 32% of the patients, was mainly mild to moderate in severity, manageable with standard recommendations, and all events resolved within a maximum of seven days. Patients treated with 90mg ALLO-647 did not experience an increase in infection as compared to those treated with 39mg ALLO-647.

Four patients (18%) experienced serious adverse events (SAE). One patient had Grade 2 pyrexia and Grade 2 cytomegalovirus (CMV) reactivation which resolved in two days and six days, respectively. One patient had Grade 3 rotavirus infection and Grade 3 hypokalemia which resolved in 15 days and two days, respectively. One patient had Grade 3 febrile neutropenia and Grade 3 hypotension which each resolved in two days. One patient had a Grade 3 upper GI hemorrhage which resolved in one day and Grade 3 CMV reactivation which resolved in 25 days.

Adverse events were observed across all dose levels of ALLO-501 and ALLO-647. SAEs were observed at ALLO-501 cell dose level 40 x 106 and 120 x 106 and at both dose levels of ALLO-647.

"We are pleased to see the progress made by Allogene in the ALPHA trial and the positive initial data for ALLO-501," said Olivier Laureau, President of Servier. "Our teams are proud to play a role in helping to develop innovative therapies for patients in need."

Allogene is the sponsor of the Phase 1 ALPHA trial which is designed to assess the safety and tolerability at increasing dose levels of ALLO-501 and ALLO-647 in the most common NHL subtypes of relapsed/refractory diffuse large B-cell lymphoma or follicular lymphoma.

ALLO-501A is a next generation anti-CD19 AlloCAR T devoid of the rituximab recognition domains found in ALLO-501. This could allow for use in a broader patient population, including those NHL patients with recent rituximab exposure. ALLO-501A is intended for Phase 2 development and enrollment has been initiated in the Phase 1 portion of the ALPHA2 trial of ALLO-501A.

Webinar
Please register for the webinar on the Company’s website at www.allogene.com under the Investors tab in the News and Events section (View Source) or by clicking the following link directly.

The webinar will be available as a live event only and the materials presented will be available on the Allogene website prior to the start of the event.

About ALLO-501 (Allogene Sponsored)
ALLO-501 is an anti-CD19 allogeneic CAR T (AlloCAR T) therapy being jointly developed under a collaboration agreement between Servier and Allogene based on an exclusive license granted by Cellectis to Servier. ALLO-501 uses Cellectis technologies. Servier grants to Allogene exclusive rights to ALLO-501 in the U.S. while Servier retains exclusive rights for all other countries.

Phio Announces Positive In Vivo Data on the Intratumoral Use of INTASYL Compounds Showing Strong Antitumor Activity

On May 29, 2020 Phio Pharmaceuticals Corp. (Nasdaq: PHIO), a biotechnology company developing the next generation of immuno-oncology therapeutics based on its proprietary self-delivering RNAi (INTASYL) therapeutic platform, reported positive data from in vivo studies that show strong antitumoral efficacy with several of its INTASYL pipeline programs, including PH-762, PH-894 and PH-804 (Press release, Phio Pharmaceuticals, MAY 29, 2020, View Source [SID1234558696]). These results show that intratumoral delivery of INTASYL compounds inhibited tumor growth by overcoming the immunosuppressive tumor microenvironment (TME) as shown by changes in T cell composition and activation. Therefore, the Company believes these pipeline programs show great promise in the treatment of solid tumors. These data were presented during the ASCO (Free ASCO Whitepaper) 2020 Virtual Scientific Program (Abstract e15206: "Intratumoral use of self-delivering RNAi to reprogram the tumor microenvironment and boost the antitumor response").

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The Company’s pipeline programs PH-762, PH-894 and PH-804 are INTASYL compounds designed to silence the expression of PD-1, BRD4 and TIGIT, respectively, which are proteins linked to reduced immune cell function in cancer patients. A series of preclinical in vivo studies in tumor models were conducted and the resulting data showed dose-dependent attenuated tumor growth for the INTASYL compounds compared to control groups. Relevant changes in the TME include an increase of tumor-infiltrating lymphocytes, including CD8+ T cells, responsible for tumor cell killing, and an increase of activation markers on these cells. Together, these novel findings support using INTASYL intratumorally as a viable approach to immunotherapy and warrant further investigation in patients.

"These exciting new data show that INTASYL compounds are able to overcome the immunosuppressive TME by reprogramming T cells in order to inhibit tumor growth. These data support our belief that Phio’s INTASYL technology can be used to develop powerful immunotherapeutics, which can overcome the shortcomings of currently available systemic immunotherapy," said Dr. Simon Fricker, Phio’s VP of Research. "We look forward to continuing our development of INTASYL, including the IND enabling studies which are currently ongoing."

A poster further detailing the data presented at the ASCO (Free ASCO Whitepaper) 2020 Virtual Scientific Program will be made available under the "Investors – Events and Presentations" section of the Company’s website (click here).

Kintor Pharma Stages $240 Million Hong Kong IPO for Androgen Receptor Drugs

On May 29, 2020 Suzhou Kintor Pharma reported that it has completed a $240 million IPO on the Hong Kong Exchange (Press release, Suzhou Kintor Pharmaceuticals, MAY 29, 2020, View Source [SID1234558695]). Kintor is focused on androgen receptor related diseases including prostate cancer, breast cancer, liver cancer and alopecia. Its pipeline includes novel small molecule drugs, biologics and combination therapies. Kintor expects its lead drug, a prostate cancer candidate known as proxalutamide, will be approved for China commercialization later this year. The IPO was more than 500 times oversubscribed, and Kintor’s shares rose slightly in initial trading

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Heat Biologics Presents Positive Survival Benefit for HS-110 in Combination with Nivolumab in Phase 2 Lung Cancer Trial at 2020 American Society of Clinical Oncology (ASCO) Annual Meeting

On May 29, 2020 Heat Biologics, Inc. ("Heat") (NASDAQ:HTBX), a clinical-stage biopharmaceutical company focused on developing first-in-class therapies to modulate the immune system, including multiple oncology product candidates and a novel COVID-19 vaccine, reported its latest data at the ASCO (Free ASCO Whitepaper) Annual Meeting (Press release, Heat Biologics, MAY 29, 2020, View Source [SID1234558694]). The poster presentation can be viewed on the ASCO (Free ASCO Whitepaper) meeting website at: View Source and on Heat Biologics’ website at: View Source

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HS-110 is an "off-the-shelf" allogeneic cell-based therapy designed to activate patients’ immune system against multiple cancer testis antigens (CTAs) to elicit a diverse and robust T-cell attack against tumor cells. A Phase 2 trial of HS-110 in combination with Bristol-Myers Squibb’s (BMS) Opdivo (nivolumab) for multiple treatment settings in advanced non-small cell lung cancer (NSCLC) is ongoing, with enrollment of this trial completed in July 2019.

This data demonstrated that significant survival benefit was observed in a cohort of previously treated, checkpoint inhibitor (CPI) naïve patients with advanced NSCLC; with a median overall survival (mOS) of 28.7 months for the intent-to-treat (ITT) patients (N = 47). This data compares favorably with published data of Checkmate 057, which reported a mOS of 12.2 months in patients who received nivolumab as single agent in a similar treatment setting. Notably, a statistically significant survival benefit with mOS of 42.1 months was observed in patients with injection site reaction (p = 0.0001). Exploratory biomarker analyses showed that overlapping CTA expression in patients’ tumors at baseline with HS-110, as well as the expression of a specific CTA were both associated with statistically significant improved overall survival (p = 0.028 and 0.008, respectively).

"Our exploratory biomarker analysis solidly establishes additional clinical evidence for the HS-110 mechanism of action," said Jeff Hutchins, Chief Scientific and Operating Officer of Heat. "This extended mOS also suggests that HS-110 treatment in combination with a CPI should be considered for any solid tumor type with sufficient CTA overlap with HS-110."

This study has completed enrollment, and 21 of the 47 patients enrolled (45%) are still alive as of this data cut. HS-110 now has a positive safety profile in over 200 patients, and combination of HS-110 and nivolumab appears to be safe and well-tolerated.

"This updated data demonstrates the potential utility of HS-110 in combination with a checkpoint inhibitor as a frontline treatment for NSCLC", said Jeff Wolf, Chief Executive Officer of Heat. "Heat is planning an end-of-phase 2 meeting with the FDA to discuss registration trial design."