CAMBRIDGE, Mass., July 23, 2018 (GLOBE NEWSWIRE) -- Leap Therapeutics, Inc. (Nasdaq:LPTX), a biotechnology company
developing targeted and immuno-oncology therapeutics, today announced it has entered into a collaboration agreement with Merck
KGaA, Darmstadt, Germany, and Pfizer to evaluate Leap’s GITR agonist, TRX518, in combination with avelumab*, a human anti-PD-L1
IgG1 monoclonal antibody, and chemotherapy.
Under the terms of the collaboration, Leap will be conducting a Phase I/II clinical trial in advanced solid tumors including
expansion populations in patients with relapsed/refractory ovarian, breast, and prostate cancers. The study is expected to begin
enrolling patients in the first quarter of 2019.
“The combination of TRX518 with anti-PD-L1 immunotherapy and cyclophosphamide has a solid scientific rationale and we look to
build upon our early clinical and preclinical data highlighting the potential benefits of such a combination,” commented Cynthia
Sirard, M.D., Vice President, Clinical Development of Leap Therapeutics.
“TRX518 has demonstrated encouraging potential with early clinical activity in patients with advanced solid tumors,” said Chris
Boshoff, M.D., Ph.D., Senior Vice President and Head of Immuno-oncology, Early Development and Translational Oncology, Pfizer
Global Product Development. “This collaboration with Leap Therapeutics to evaluate TRX518 in combination with avelumab gives us the
opportunity to investigate a potential novel immunotherapy treatment regimen as we pursue our mission of improving outcomes for
patients living with hard-to-treat cancers.”
“Combination therapy remains a major focus in our clinical development program for avelumab in an effort to advance the
treatment landscape for patients with challenging cancers,” said Alise Reicin, Head of Global Clinical Development at the Biopharma
business of Merck KGaA, Darmstadt, Germany, which in the US and Canada operates as EMD Serono. “Through our collaboration with Leap
Therapeutics, we are eager to further understand the potential of this novel immunotherapy combination in this patient
population.”
Avelumab has received accelerated approval** by the US Food and Drug Administration (FDA) for the treatment of patients with
metastatic Merkel cell carcinoma (MCC) and previously treated patients with locally advanced or metastatic urothelial carcinoma
(mUC), and is under further clinical evaluation across a range of tumor types under a global strategic alliance between Merck KGaA,
Darmstadt, Germany, and Pfizer.
*Avelumab is under clinical investigation for treatment of solid tumors and hematological malignancies in combination with
TRX518 and has not been demonstrated to be safe and effective for these uses. There is no guarantee that avelumab will be approved
for solid tumors or hematological malignancies by any health authority worldwide.
About Avelumab
Avelumab is a human anti-programmed death ligand-1 (PD-L1) antibody. Avelumab has been shown in preclinical models to engage
both the adaptive and innate immune functions. By blocking the interaction of PD-L1 with PD-1 receptors, avelumab has been shown to
release the suppression of the T cell-mediated antitumor immune response in preclinical models.1-3 Avelumab has also
been shown to induce NK cell-mediated direct tumor cell lysis via antibody-dependent cell-mediated cytotoxicity (ADCC) in
vitro.3-5 In November 2014, Merck KGaA, Darmstadt, Germany, and Pfizer announced a strategic alliance to co-develop and
co-commercialize avelumab.
Avelumab is currently being evaluated in the JAVELIN clinical development program, which involves at least 30 clinical programs,
including seven Phase III trials, and over 8,600 patients across more than 15 different tumor types. For a comprehensive list of
all avelumab trials, please visit clinicaltrials.gov.
Approved Indications in the US**
The US Food and Drug Administration (FDA) granted accelerated approval for avelumab (BAVENCIO®) for the treatment of
(i) mMCC in adults and pediatric patients 12 years and older and (ii) patients with locally advanced or metastatic urothelial
carcinoma (UC) who have disease progression during or following platinum-containing chemotherapy, or who have disease progression
within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. These indications were approved under
accelerated approval based on tumor response rate and duration of response. Continued approval for these indications may be
contingent upon verification and description of clinical benefit in confirmatory trials.
Important Safety Information from the US FDA Approved Label
The warnings and precautions for avelumab (BAVENCIO®) include immune-mediated adverse reactions (such as pneumonitis, hepatitis,
colitis, endocrinopathies, nephritis and renal dysfunction and other adverse reactions), infusion-related reactions and
embryo-fetal toxicity.
Common adverse reactions (reported in at least 20% of patients) in patients treated with BAVENCIO for mMCC and patients with
locally advanced or metastatic UC include fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reaction, peripheral
edema, decreased appetite/hypophagia, urinary tract infection and rash.
For full prescribing information and medication guide for BAVENCIO, please see www.BAVENCIO.com.
Alliance between Merck KGaA, Darmstadt, Germany, and Pfizer Inc., New York, US
Immuno-oncology is a top priority for Merck KGaA, Darmstadt, Germany, and Pfizer Inc. The global strategic alliance between
Merck KGaA, Darmstadt, Germany, and Pfizer Inc., New York, US, enables the companies to benefit from each other's strengths and
capabilities and further explore the therapeutic potential of avelumab, an anti-PD-L1 antibody initially discovered and developed
by Merck KGaA, Darmstadt, Germany. The immuno-oncology alliance will jointly develop and commercialize avelumab and advance
Pfizer's PD-1 antibody. The alliance is focused on developing high-priority international clinical programs to investigate avelumab
as a monotherapy, as well as in combination regimens, and is striving to find new ways to treat cancer.
About Leap Therapeutics
Leap Therapeutics (NASDAQ:LPTX) is focused on developing targeted and immuno-oncology therapeutics. Leap’s most advanced
clinical candidate, DKN-01, is a humanized monoclonal antibody targeting the Dickkopf-1 (DKK1) protein, a Wnt pathway modulator.
DKN-01 is in clinical trials in patients with esophagogastric cancer, biliary tract cancer, and gynecologic cancers, with an
emerging focus on patients with defined mutations of the Wnt pathway and in combination with immune checkpoint inhibitors. Leap’s
second clinical candidate, TRX518, is a novel, humanized GITR agonist monoclonal antibody designed to enhance the immune system’s
anti-tumor response that is in two advanced solid tumor studies.
FORWARD-LOOKING STATEMENTS
This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, Section
21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995, which involve risks and
uncertainties. These statements include statements regarding Leap’s expectations with respect to the development and advancement of
DKN-01 and TRX518, including the initiation, timing, design and results of future studies, enrollment in future studies, business
development, and other future expectations, plans and prospects. Although Leap believes that the expectations reflected in such
forward-looking statements are reasonable as of the date made, forward-looking statements are subject to known and unknown risks,
uncertainties and other factors that could cause actual results to differ materially from our expectations. Such risks and
uncertainties include, but are not limited to: the outcome, cost, and timing of our product development activities and clinical
trials; the uncertain clinical development process, including the risk that clinical trials may not have an effective design or
generate positive results; our ability to obtain and maintain regulatory approval of our drug product candidates; our plans to
research, develop, and commercialize our drug product candidates; our ability to achieve market acceptance of our drug product
candidates; unanticipated costs or delays in research, development, and commercialization efforts; the applicability of clinical
study results to actual outcomes; the size and growth potential of the markets for our drug product candidates; our ability to
continue obtaining and maintaining intellectual property protection for our drug product candidates; and other risks. Detailed
information regarding factors that may cause actual results to differ materially will be included in Leap Therapeutics’ periodic
filings with the Securities and Exchange Commission (the "SEC"), including Leap Therapeutics’ Form 10-K that Leap filed
with the SEC on February 23, 2018. Any forward-looking statements contained in this release speak only as of its date. We undertake
no obligation to update any forward-looking statements contained in this release to reflect events or circumstances occurring after
its date or to reflect the occurrence of unanticipated events.
CONTACT:
Douglas E. Onsi
Chief Financial Officer
Leap Therapeutics, Inc.
donsi@leaptx.com
617-714-0360
Argot Partners
Investor Relations
Heather Savelle or Mary Jenkins
212-600-1902
heather@argotpartners.com
mary@argotpartners.com
References
- Dolan DE, Gupta S. PD-1 pathway inhibitors: changing the landscape of cancer immunotherapy. Cancer Control
2014;21(3):231-7.
- Dahan R, Sega E, Engelhardt J et al. FcγRs modulate the anti-tumor activity of antibodies targeting the PD-1/PD-L1 axis.
Cancer Cell 2015;28(3):285-95.
- Boyerinas B, Jochems C, Fantini M et al. Antibody-dependent cellular cytotoxicity activity of a novel anti-PD-L1 antibody
avelumab (MSB0010718C) on human tumor cells. Cancer Immunol Res 2015;3(10):1148-57.
- Kohrt HE, Houot R, Marabelle A et al. Combination strategies to enhance antitumor ADCC. Immunotherapy 2012;4(5):511-27.
- Hamilton G, Rath B. Avelumab: combining immune checkpoint inhibition and antibody-dependent cytotoxicity. Expert Opin Biol
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