On June 04, 2016 Celldex Therapeutics, Inc. (Nasdaq:CLDX) reported results from a Phase 2 clinical study evaluating CDX‑1401 and CDX‑301 in patients with malignant melanoma, which was conducted by the Cancer Immunotherapy Trials Network (CITN) under a Cooperative Research and Development Agreement (CRADA) between Celldex and the Cancer Therapy Evaluation Program of the National Cancer Institute (Press release, Celldex Therapeutics, JUN 4, 2016, View Source [SID:1234512995]). CDX‑1401 is an NY‑ESO‑1-antibody fusion protein for immunotherapy, and CDX‑301 (recombinant human Flt3 ligand) is a potent hematopoietic cytokine that uniquely expands dendritic cells and hematopoietic stem cells. Results from the study were presented at the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago in a poster titled "A Phase 2, Open-label, Multicenter, Randomized Study of CDX‑1401, a Dendritic Cell Targeting NY‑ESO‑1 Vaccine, in Patients with Malignant Melanoma Pre-Treated with CDX‑301, a Recombinant Human Flt3 Ligand."

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The study randomized 60 patients with resected stage IIb through IV melanoma into two cohorts (n=30 each) to assess whether the immune response to NY-ESO-1 elicited by CDX-1401 could be substantially increased by pre-treatment with CDX-301 to expand the number of dendritic cells, which are key cells in initiating immune responses. As this study was intended primarily for safety and immune endpoints, patients were not selected for NY‑ESO‑1 expression. Both treatment cohorts received four monthly cycles of CDX‑1401 and poly-ICLC (Hiltonol). Cohort 1 received pre-treatment with CDX‑301 for the first two cycles, whereas Cohort 2 did not receive CDX‑301. Both combination regimens were well tolerated, and no drug-related adverse events required discontinuation from treatment.

NY-ESO-1 specific T cell responses were significantly greater and developed earlier in Cohort 1 compared to Cohort 2. In addition, all patients in Cohort 1 (n=30) achieved a specific NY-ESO-1-specific T cell response compared to 22 out of 30 patients in Cohort 2. Substantial increases in innate immune cells (dendritic cells, natural killer cells and monocytes) and greater increases in antibody titer were observed in the CDX‑301 pre-treated Cohort 1.

"The Cancer Immunotherapy Trials Network has prioritized CDX-301 as a dendritic cell growth factor. The current study validates that Flt3 ligand can greatly expand peripheral blood dendritic cells and is highly effective at immunizing cancer antigen specific T cells when combined with CDX-1401, the immunotherapy that delivers NY‑ESO‑1 to dendritic cells," said Martin "Mac" Cheever, M.D., a member of the Vaccine and Infectious Disease Division at Fred Hutchinson Cancer Research Center, Professor of Medicine at the University of Washington and Director of the Fred Hutch-based Cancer Immunotherapy Trials Network. "These results, which show rapid cellular immune responses in a majority of patients, should stimulate significant interest in what appears to be a highly applicable, effective immunologic approach."

"This study confirms that CDX-1401 is effective at driving NY-ESO-1 immunity and further shows the value of CDX-301 as a combination agent for enhancing tumor-specific immune responses," said Thomas Davis, M.D., Executive Vice President and Chief Medical Officer of Celldex Therapeutics. "With these results, we are initiating a targeted study in patients with NY‑ESO‑1 positive disease to determine if these enhanced immune responses can translate to improved clinical outcomes. This also provides exciting new opportunities for use of CDX-301 in other combination immunotherapy regimens."

The poster is available on the "Publications" page of the "Science" section of the Celldex website.

About CDX‑301
CDX‑301 (Flt3L) is a potent hematopoietic cytokine that has demonstrated a unique capacity to increase the number of circulating dendritic cells in both laboratory and clinical studies. In addition, CDX‑301 has shown impressive results in models of cancer, infectious diseases and inflammatory/autoimmune diseases. Celldex believes this ligand may hold significant opportunity for synergistic development in combination with other proprietary molecules in the Company’s portfolio.

About CDX‑1401
CDX‑1401 is an NY‑ESO‑1-antibody fusion protein for immunotherapy, which is designed to activate the patient’s immune system against cancers that express the tumor marker, NY‑ESO‑1. CDX‑1401 consists of a fully human monoclonal antibody with specificity for the dendritic cell receptor DEC‑205 genetically linked to the NY‑ESO‑1 tumor antigen. Celldex has accessed NY‑ESO‑1 through a licensing agreement with the Ludwig Institute for Cancer Research. By selectively delivering the NY‑ESO‑1 antigen to dendritic cells in the body, CDX‑1401 is intended to induce robust immune responses against the antigen-expressing cancer cells.

On June 4, 2016 Pfizer Inc. (NYSE:PFE) reported results from a Phase 1b trial of Pfizer’s investigational immunotherapy agent utomilumab (the proposed non-proprietary name for PF-05082566), a 4-1BB (also called CD137) agonist, in combination with pembrolizumab, a PD-1 inhibitor, in patients with advanced solid tumors (Press release, Pfizer, JUN 4, 2016, View Source [SID:1234513014]). This is the first reported study of a 4-1BB agonist combined with a checkpoint inhibitor. Encouraging safety data from the study were shared today as an oral presentation at the 52nd Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in Chicago.

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"While these are early data, the combination of utomilumab with pembrolizumab demonstrates an encouraging safety profile and an early indication of potential anti-tumor activity across solid tumors," said Anthony W. Tolcher, M.D., director of clinical research at South Texas Accelerated Research Therapeutics (START) San Antonio. "We believe these results warrant further investigation to confirm whether combining utomilumab with a checkpoint inhibitor may amplify anti-tumor responses."

Of the 23 patients enrolled in the trial, six had a confirmed complete or partial response. The majority (four of six) of these responses lasted at least six months, with two patients maintaining their response for nearly one year at the time of data cut off. Treatment emergent adverse events were generally mild and did not appear to increase with higher doses of utomilumab, and no dose-limiting toxicity was reported.

"Pfizer believes that bringing the promise of immunotherapies for cancer to more patients will occur through combining agents that work on different pathways within the immune system," said Chris Boshoff, vice president and head of Early Development, Translational and Immuno-Oncology for Pfizer Oncology. "We are exploring numerous utomilumab combinations in order to better understand its potential role in mobilizing the immune system against difficult-to-treat cancers."

Pfizer is investigating utomilumab in both hematologic cancers and solid tumors in several planned and ongoing trials. It is being evaluated as a single agent across multiple tumors, in combination with rituximab in lymphoma,1 and in combination with other immunotherapies (e.g., OX40 agonist [PF-04518600], anti-CCR4 [mogamulizumab] and avelumab, an investigational fully human anti-PD-L1 IgG1 monoclonal antibody being developed through an alliance between Merck KGaA, Darmstadt, Germany, and Pfizer) in various solid tumors and hematological malignancies.2,3,4 The mogamulizumab/utomilumab combination is a collaboration with Kyowa Hakko Kirin, Japan.3

About the Study

This Phase 1b dose-escalation study assessed overall safety, pharmacokinetics, pharmacodynamics and anti-tumor activity of utomilumab in combination with pembrolizumab in 23 patients with advanced solid tumors (non-small cell lung, renal cell carcinoma, head and neck, pancreatic, anaplastic thyroid, small-cell lung, colon, sarcoma, thymoma and melanoma). The primary objective was to estimate the maximum tolerated dose and select the recommended Phase 2 dose. Patients received utomilumab (0.45 to 5.0 mg/kg) and pembrolizumab (2 mg/kg) intravenously on day one of 21-day cycles. The number of cycles patients have received across all doses ranged from two to 19, and five patients remain on treatment (maximum dosing is 32 cycles).

The six confirmed responses included two complete responses in one patient with small cell lung cancer and one patient with renal cell carcinoma; partial responses were observed in one patient each with renal cell carcinoma, non-small cell lung cancer, head and neck cancer and anaplastic thyroid cancer. The most common treatment related adverse events were rash, fatigue, itching, fever, decreased appetite and nausea, with none reported as Grade 3 or 4. No patients discontinued due to treatment related toxicity.

About Utomilumab

Utomilumab (PF-05082566) is a fully human monoclonal antibody (mAb) agonist that selectively binds to 4-1BB (also called CD137), a protein receptor expressed in many cancer-fighting T cells. When a 4-1BB agonist binds to CD137, it has been observed to stimulate and increase the number of T cells, which is believed to accelerate the immune response to attack and kill cancer cells. In preclinical models, utomilumab has shown anti-tumor activity by enhancing T cell mediated immune responses.5,6,7 Utomilumab is being studied in combination with checkpoint inhibitors, which act on another immune signaling pathway and are believed to work by blocking signals from cancer cells which inhibit the host immune system. This signal blockade may allow the host immune system to attack cancer cells.

Learn more about how Pfizer Oncology is applying innovative approaches in an effort to improve the outlook for people living with cancer at View Source

On June 04, 2016 Momenta Pharmaceuticals, Inc. (NASDAQ:MNTA), a biotechnology company specializing in the characterization and engineering of complex drugs, reported final data from the Phase 1 trial evaluating necuparanib in combination with nab-paclitaxel (nabP; Abraxane) and gemcitabine (gem) in patients with advanced metastatic pancreatic cancer (ClinicalTrials.gov Identifier NCT01621243) at the 2016 ASCO (Free ASCO Whitepaper) Annual Meeting, from 8:00 to 11:30 am CDT (Abstract #4117 / Poster #109) in Chicago, IL (Press release, Momenta Pharmaceuticals, JUN 4, 2016, View Source [SID:1234513080]).

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"The final data read out from the Phase 1 study continues to show favorable tolerability and promising antitumor activity as assessed by survival and response data," said Eileen O’Reilly, MD of David M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center and lead author on the poster. "We also continued to see a clinically meaningful reduction in levels of CA19.9, a predictive biomarker that often correlates with the long-term outcome and response to treatment in pancreatic cancer patients."

Necuparanib was administered daily in combination with 125 mg/m2 nabP and 1000 mg/m2 gem (Days 1, 8, and 15 of each 28-day cycle). The necuparanib starting dose was 0.5 mg/kg, which was increased until the maximum tolerated dose of 5 mg/kg was determined. nabP was added to the treatment regimen starting with the third cohort. Thirty-nine patients (12 patients in the first two cohorts and 27 patients in the five subsequent cohorts) received necuparanib and were included in the analyses. Top-line results included:

Necuparanib was well tolerated when added to standard of care; no increases in incidence, severity, or duration for known adverse events of gem or nabP + gem were observed when combined with necuparanib.
Measurable levels of necuparanib were seen starting at the 2 mg/kg dose group. Release of heparin-binding protein (a pharmacodynamic marker) increased with increasing doses and plateaued at 4-5 mg/kg.
Encouraging signals of activity were observed:
16 patients treated with necuparanib + nabP + gem completed Cycle 1 and had ≥1 scan on treatment; 9 (56%) achieved RECIST partial response (PR) and 5 (31%) achieved stable disease, for a disease control rate (DCR) of 14/16 (88%); median OS in this subset was 15.6 months. Median OS of patients treated with ≥1 dose of necuparanib + nabP + gem (n=24) was 13.1 months.
24-month survival rates for patients treated with ≥1 cycle and ≥1 dose of necuparanib + nabP + gem were 25% and 21%, respectively.
Of 15 CA19.9 evaluable patients, 15 (100%) had ≥20%, 14 (93%) had ≥50%, and 7 (47%) had ≥90% decreases from baseline.
"We continue to be encouraged by these data from our lead novel drug candidate, and look forward to completing enrollment of the Phase 2 study over the next several months," said Jim Roach, M.D., Senior Vice President of Development and Chief Medical Officer of Momenta Pharmaceuticals. "We expect to report key results from the Phase 2 study in the second half of 2017."

About Necuparanib
Necuparanib (M402) is a novel oncology drug candidate engineered to have a broad range of effects on tumor cells. The use of heparins to treat venous thrombosis in cancer patients has generated numerous reports of antitumor activity; however, the dose of these products has been limited by their anticoagulant activity. Leveraging its experience in deciphering the structure-function relationships of complex therapeutics, Momenta engineered necuparanib from unfractionated heparin to have significantly reduced anticoagulant activity while preserving relevant antitumor properties associated with heparins. A Phase 2, randomized, double-blind, controlled study in pancreatic cancer is ongoing, which will evaluate the antitumor activity of necuparanib in combination with nab-paclitaxel (Abraxane) plus gemcitabine, versus nab-paclitaxel plus gemcitabine alone. Necuparanib has received Orphan Drug and Fast Track designations from the U.S. Food and Drug Administration (FDA) for the treatment of pancreatic cancer.

On June 4, 2016 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that it is presenting data from across its cancer immunotherapy pipeline highlighting its multipronged combination approach to cancer immunotherapy treatment (Press release, Hoffmann-La Roche , JUN 4, 2016, View Source [SID:1234512997]). The first combination trial evaluated Tecentriq with targeted therapy Cotellic in a phase Ib study in people with mCRC who had been heavily pretreated. The study demonstrated a tolerable safety profile with an Overall Response Rate (ORR) of 17 percent (n=4). All responders had the KRAS gene mutation, and responses were observed irrespective of Microsatellite Instability (MSI) status. Responses were ongoing in two out of four people at the time of data analysis. The second evaluated a combination with Tecentriq and Abraxane chemotherapy in a phase Ib study for people with mTNBC. The results showed that the safety profile was similar to that previously seen with Tecentriq or Abraxane chemotherapy alone. An ORR of 38% (n=32) was observed across all lines of therapy. The final combination being presented are dose-escalation results from the ongoing phase Ib study of the investigational Roche cancer immunotherapy molecule (MOXR0916, anti-OX40) and Tecentriq. The data showed a favourable safety profile and evidence of immune activation, supporting the continuation of further investigation into the potential benefits this combination could bring to patients.

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"Combinations based on a deep understanding of the science are a central component of our cancer immunotherapy development strategy.’’ said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "We believe we may be able to bring the full potential of treatments such as Tecentriq to a greater number of people by exploiting different mechanisms of action in combination, such as with chemotherapy, targeted treatments and other immunotherapy agents.’’

Further information on Roche’s contribution to the ASCO (Free ASCO Whitepaper) 2016 scientific programme, the company’s wider progress in cancer care and key data being presented at the conference will be featured at a Roche investor briefing on Sunday 5 June between 6pm – 8pm CDT. This event is independently organised by Roche and is open to analysts attending the ASCO (Free ASCO Whitepaper) 2016 Annual Meeting. To register for the Roche investor briefing, please use the following link:
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To learn more about Roche’s personalised cancer immunotherapy programme and Roche’s contribution to ASCO (Free ASCO Whitepaper) 2016, please follow Roche on Twitter via @Roche. You can keep up to date with ASCO (Free ASCO Whitepaper) 2016 Annual Meeting news and updates by using the hashtag #ASCO16.

About the phase Ib combination study of Tecentriq with Cotellic in advanced CRC
Overview and study design
A phase Ib, open-label, multicentre study designed to assess the safety, tolerability and pharmacokinetics of co-administration of intravenous dosing of Tecentriq and oral dosing of Cotellic in participants with metastatic or locally advanced cancer for which standard therapies have been exhausted

The primary endpoints of the study were safety and tolerability with secondary endpoints including ORR confirmed by RECIST v1.1

23 CRC (22 KRAS mutant, one wild type) patients were enrolled during escalation and expansion

Cobimetinib was escalated from 20 mg to 60 mg daily (21 days on/7 days off) and combined with Tecentriq 800 mg IV q2w

About the phase Ib combination study of Tecentriq with Abraxne in mTNBC
Overview and study design

GP28328 (NCT01633970) was a multi-centre, multi-arm study evaluating Tecentriq in combination with Abraxane chemotherapy. Arm F consisted of patients with TNBC (up to 3 prior lines of chemotherapy were allowed)

— The primary endpoint was safety and tolerability

— Secondary endpoints included efficacy per RECIST v1.1 criteria (best overall response, objective response rate, duration of response, progression-free survival) and immune-related response criteria (irRC), pharmacokinetics and biomarker analyses

About the phase Ib study of MOXR0916 (OX40) and Tecentriq in advanced solid tumours
Overview and study design

A phase Ib, open-label, multicentre study evaluating the safety and pharmacokinetics of MOXR0916 and Tecentriq in patients with locally advanced or metastatic solid tumours

The primary endpoint of the study is safety and tolerability,

A 3+3 dose-escalation was conducted with a 21-day window to evaluate dose-limiting toxicity

— Escalating doses of MOXR0916 in combination with a fixed 1200 mg dose of Tecentriq were administered every three weeks (q3w)

An expansion cohort to enable immune profiling of serial tumour biopsies was also enrolled

28 patients were treated in eight dose-escalation cohorts (MOXR0916 dose levels 0.8–1200 mg) and 23 additional patients were treated in the serial biopsy cohort

— The median number of prior therapies for metastatic disease was two (range 0–7) and nine patients had received prior PD-1/PD-L1 antibodies

Results:
No dose-limiting toxicities, Grade 4/5 adverse events (AEs) attributed to study treatment or related AEs leading to treatment discontinuation were reported

— The majority of treatment-related AEs were Grade 1 in severity; one related Grade 3 event (pneumonitis responsive to corticosteroids) was reported

Evidence of immune activation, including upregulation of PD-L1, was observed in paired tumour biopsies from some patients, including patients whose immediate prior therapy was anti-PD-1

The regimen selected for dose expansion is MOXR0916 300 mg + Tecentriq 1200 mg q3w. Evaluation of efficacy is ongoing in expansion cohorts for patients with melanoma, RCC, NSCLC, urothelial carcinoma, and TNBC.

About Roche in cancer immunotherapy
For more than 50 years, Roche has been developing medicines with the goal to redefine treatment in oncology. Today, we’re investing more than ever in our effort to bring innovative treatment options that help a person’s own immune system fight cancer.

About personalised cancer immunotherapy
The aim of personalised cancer immunotherapy (PCI) is to provide individual patients with treatment options that are tailored to their specific needs. The Roche PCI research and development programme comprises more than 20 investigational candidates, nine of which are in clinical trials. All studies include the prospective evaluation of biomarkers to determine which people may be appropriate candidates for Roche medicines. In the case of Tecentriq, PCI begins with the PD-L1 (programmed death ligand-1) IHC assay based on the SP142 antibody developed by Roche Tissue Diagnostics. The goal of PD-L1 as a biomarker is to identify those people most likely to experience clinical benefit with Tecentriq as a single agent versus those who may benefit more from combination approaches; the purpose is to inform treatment strategies which will give the greatest number of patients a chance for transformative benefit. The ability to combine TECENTRIQ with multiple chemotherapies may provide new treatment options to people across a broad range of tumours regardless of their level of PD-L1 expression.

PCI is an essential component of how Roche delivers on the broader commitment to personalised healthcare.

About Tecentriq (atezolizumab)
Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1. Tecentriq is designed to directly bind to PD-L1 expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the activation of T cells. Tecentriq may also affect normal cells.

About MOXR0916 (anti-OX40)
MOXR0916 is an agonist monoclonal antibody that targets OX40, a costimulatory receptor that is expressed by T cells, and results in activation rather than blockade of the OX40 signaling pathway. MOXR0916 is thought to promote anti-tumour immunity by binding to OX40 on both antigen-experienced effector T cells, thereby enhancing their proliferation and survival, and on activated regulatory T cells, thereby inhibiting their suppressive function. Because Tecentriq and MOXR0916 act through distinct but complementary mechanisms, in combination these investigational immunotherapies have the potential to enhance activation of CD8+ T-cells that mediate anti-tumour immune responses.

On June 04, 2016 Stemline Therapeutics, Inc. (Nasdaq:STML) reported the oral presentation of positive clinical data from its ongoing SL-401 Phase 2 potentially pivotal clinical trial in blastic plasmacytoid dendritic cell neoplasm (BPDCN) (Press release, Stemline Therapeutics, JUN 4, 2016, View Source [SID:1234513081]). The Phase 2 trial results were delivered today by Naveen Pemmaraju, M.D. from the University of Texas MD Anderson Cancer Center, via an oral presentation at the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting in Chicago, IL.

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The data presented at ASCO (Free ASCO Whitepaper) cover 24 BPDCN patients treated with SL-401 (19 evaluable for response, 4 recently treated/efficacy assessment pending, and 1 non-evaluable patient). Results demonstrate that SL-401 produced an 89% (17/19) overall response rate (ORR) in BPDCN, with a 100% (12/12) ORR in first-line patients and a 71% (5/7) ORR in relapsed/refractory patients, including one compassionate use patient (see Table 1). In 12 evaluable first-line patients (all doses), there were 9 complete responses (CR) and 2 clinical complete responses (CRc). CRc is defined as a CR in non-skin affected organs with marked gross clearance of skin lesions and residual microscopic skin disease. In the 10 evaluable first-line patients treated at 12 ug/kg/day, the CR/CRc rate was 100% (8 CR and 2 CRc). In the 7 evaluable relapsed/refractory BPDCN patients, including one treated on a compassionate use basis, the ORR rate was 71%, which included 1 CR and 1 CRc (29% CR/CRc rate) and 3 partial responses (PR).

Response duration data continue to mature and appear promising. 75% (9/12) first-line BPDCN patients treated at 12 ug/kg/day remained relapse-free (1+-13+ months). This includes five patients receiving ongoing SL-401 therapy (1+-9+ months; 1+-12+ cycles), and four patients who were successfully bridged to stem cell transplant (SCT) and remain in remission (6+-13+ months after the first dose of SL-401 and 1+-7+ months post-SCT). In the relapse/refractory setting, 43% (3/7) of patients were progression-free and receiving ongoing SL-401 (0.5+-3+ months). Patients are being followed for progression free survival (PFS) and overall survival (OS) which, while early, are both trending favorably.

The most common side effects were transaminitis and hypoalbuminemia (see Table 2), which were both largely transient and not dose limiting. Dosing and safety parameters were developed during the lead-in stage of the study to minimize the risk of severe capillary leak syndrome. Since implementation of these measures, SL-401 at doses of 12 ug/kg/day has demonstrated a manageable safety and tolerability profile. Also, multiple consecutive cycles of SL-401 at 12 ug/kg/day were not associated with cumulative side effects.

Naveen Pemmaraju, M.D., Assistant Professor, Department of Leukemia at the University of Texas MD Anderson Cancer Center (Houston, TX), an investigator on the study, commented, "SL-401’s remarkable results to date suggest the agent could very well emerge as the standard of care for both first-line and relapsed/refractory BPDCN, a devastating disease for which there had previously been no effective therapy. Overall, we continue to see very strong activity with SL-401 in both first line and relapsed/refractory patients, and the safety profile continues to be manageable over increasing patient experience. Notably, we have also been able to successfully bridge several patients to transplant which, for the most part, has not been possible at this frequency with existing therapies." Dr. Pemmaraju continued, "We look forward to working closely with Stemline to bring this promising new agent to patients as quickly as possible in BPDCN and other malignancies."

Andrew A. Lane, M.D., Ph.D., Assistant Professor, Medical Oncology at the Dana-Farber Cancer Institute (Boston, MA), and a co-author on the study, commented, "The SL-401 clinical data in first-line and relapsed/refractory BPDCN continues to demonstrate exciting outcomes in these two underserved patient populations, and represents a promising new option for patients with this devastating disease." Dr. Lane continued, "We are very pleased to be ongoing contributors to this study, and look forward to helping to advance this active agent in both BPDCN and other hematologic malignancies as well."

Ivan Bergstein, M.D., Stemline’s Chief Executive Officer, commented, "We are excited by SL-401’s continued robust clinical data in all lines of BPDCN. SL-401 appears to be a potent agent, demonstrating a rapid onset of action and promising response durability, while its tolerability profile makes it well-suited for either long-term use or bridging BPDCN patients to transplant." Dr. Bergstein concluded, "Over the remainder of the year, we will continue to enroll first-line and relapsed/refractory patients in this ongoing trial, ramp up our disease awareness efforts, and advance our ongoing regulatory interactions in order to bring this agent to market as soon as possible in both settings."

The tables below summarize efficacy and safety observed in the Phase 2 potentially pivotal trial in BPDCN. Enrollment is ongoing and additional data will be available throughout 2016.

Table 1. Overview of SL-401 Clinical Activity in BPDCN

Major objective responses

89% (17/19) ORR in BPDCN (all lines/all doses)
4 additional recently-treated patients (2 first-line and 2 R/R) not yet evaluable for response
100% (12/12) ORR in first-line BPDCN (all doses)
100% (10/10) CR/CRc rate in first-line BPDCN (12 ug/kg/day)
71% (5/7) ORR in R/R BPDCN
29% (2/7) CR/CRc rate in R/R BPDCN
Response duration data maturing

75% (9/12) first-line BPDCN patients treated at 12 ug/kg/day were progression-free (1+-13+ months). This includes:
5 patients receiving ongoing SL-401 therapy (1+-9+ months; 1+-12+ cycles); and
4 patients who were successfully bridged to stem cell transplant (SCT) and remain in remission (6+-13+ months post-first SL-401 dose; 1+-7+ months post-SCT).
43% (3/7) of R/R BPDCN patients were progression-free and receiving ongoing SL-401 (0.5+-3+ months)
Patients continue to be followed for progression free survival (PFS) and overall survival (OS) and, while early, both are trending favorably

Line of Therapy All lines First-line First-line R/R1
Dose Group All Doses All Doses 12 ug/kg 12 ug/kg
n (total) 242 15 12 9
n (evaluable) 19 12 10 7
ORR 89 % 100 % 100 % 71 %
CR/CRc, n (rate) 13 (68%) 11 (92%) 10 (100%) 2 (29%)
PR 4 1 - 3
n, stem cell transplant
(SCT; auto-SCT n=3; allo-SCT n=1) 4 4 4 -
1Includes one patient treated on a compassionate use basis
2Includes 4 patients were recently treated with SL-401 and response assessment is pending

Source: ASCO (Free ASCO Whitepaper), 2016

Table 2. Overview of SL-401 Safety in BPDCN

Most Common Adverse Events (≥ 15% treatment-related adverse effects, TRAEs)
All Grades (%) Grade ≥ 3 (%)
TRAEs All AEs TRAEs All AEs
Transaminase elevation 61 74 57 61
Hypoalbuminemia 43 48 0 0
Chills 35 39 0 0
Pyrexia 30 48 0 0
Nausea 26 52 0 0
Fatigue 26 43 0 9
Thrombocytopenia 22 22 22 22
Hypotension 22 22 0 0
Weight increased 22 30 0 0
Capillary leak syndrome 22 22 9 9
Anemia 17 30 13 17
Decreased appetite 17 22 0 0
Edema peripheral 17 43 0 0