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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"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 4, 2016 Halozyme Therapeutics, Inc. (NASDAQ: HALO), a biotechnology company developing novel oncology and drug-delivery therapies, repprted results from a final analysis of 135 metastatic pancreatic cancer patients who were treated in Stage One of HALO 109-202, a phase 2 clinical study of its investigational new drug PEGPH20 in combination with ABRAXANE (nab-paclitaxel) and gemcitabine (PAG arm) as compared to ABRAXANE and gemcitabine alone (AG arm) (Press release, Halozyme, JUN 4, 2016, View Source [SID:1234513006]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

This final analysis of secondary and exploratory endpoints was conducted using the Ventana companion diagnostic to retrospectively identify high levels of hyaluronan (HA). The key results based on a February 2016 data cut-off showed in the HA-high patient population:

Median progression-free survival (PFS) was 9.2 months in the PAG arm versus 6.0 months in the AG arm, hazard ratio (HR) with a 95 percent confidence interval (CI): 0.46 (0.15, 1.40);
Overall response rate (ORR) of 50 percent, including one complete response in the PAG arm versus 33 percent and all partial responses in the AG arm;
Median duration of response (DoR) of 8.1 months in the PAG arm versus 3.7 months in the AG arm;
The exploratory analysis of median overall survival (OS) was similar between the treatment arms — 11.8 months vs. 10.9 months in the PAG vs. AG arms respectively. Factors potentially having an impact on these results include less aggressive disease among patients in the AG arm and a greater than 40 percent discontinuation rate of PEGPH20 treatment at the time of the clinical hold, resulting in all patients receiving AG alone in both arms;
The rate of thromboembolic (TE) events reduced from 43 percent to 9 percent in the PAG arm and from 25 percent to 6 percent in the AG arm with the introduction of prophylaxis with low molecular weight heparin (enoxaparin) from Stage One to Stage Two of the study.
"We are encouraged by the positive trends in this final Stage One dataset, even with PEGPH20 treatment being discontinued for more than 40 percent of patients in the PAG arm due to the prior clinical hold," said Dr. Athena Countouriotis, senior vice president and chief medical officer. "The safety profile continues to show the benefit of prophylactic enoxaparin use and the dataset continues to support our ongoing phase 3 study."

Prior interim analyses were based on patient follow up through December 2014. Results announced today include 14 months of additional follow up through February 2016. Stage One of HALO 202 enrolled a total of 146 patients between May 2013 to July 2014. The study was placed on clinical hold from April to July 2014 during which time PEGPH20 was discontinued while patients in both arms continued to receive treatment with ABRAXANE and gemcitabine alone. Stage Two enrolled a total of 133 patients as of February 2016 and Halozyme remains blinded to the overall efficacy. The company projects to report mature PFS and ORR results from Stage Two late in the fourth quarter.

Dr. Andrea Bullock, attending physician in Gastrointestinal Oncology at Beth Israel Deaconess Medical Center and an Instructor in Medicine at Harvard University said: "As one of the highest enrollers in the HALO 202 study, I am encouraged by the final data from Stage One in the HA-high patients. While the sample size remains small, the median PFS and ORR continue to favor the PEGPH20 combination treatment arm compared to the standard of care AG arm. I look forward to the Stage Two results later this year and to participating in the phase 3 global study very soon."

Halozyme’s ongoing phase 3 study, HALO 301, uses the Ventana companion diagnostic to prospectively identify HA-high patients and mirrors the design of the phase 2 study including the current inclusion/exclusion criteria; 2:1 randomization; and dosing regimens. This double-blinded placebo-controlled study plans to enroll a total of 420 patients at approximately 200 centers within 20 countries. The co-primary endpoints are PFS and OS, with a target hazard ratio of 0.59 for PFS, which is well supported by the final results from Stage One of HALO 202.

Halozyme is the only oncology biotech targeting HA, a glycosaminoglycan – or chain of natural sugars throughout the body – that can accumulate around cancer cells inhibiting other therapies. PEGPH20 is designed to degrade HA to improve the access to tumor cells for chemotherapy, monoclonal antibodies and other immuno-therapy agents.

About HALO 301
HALO 301 is a phase 3 global, randomized, double-blind placebo controlled clinical trial evaluating investigational new drug PEGPH20 as a first-line therapy for potential treatment of patients with metastatic pancreatic cancer. The trial will be conducted at approximately 200 sites with two co-primary endpoints of progression free survival and overall survival in patients receiving investigational new drug PEGPH20 in combination with gemcitabine and ABRAXANE (nab-paclitaxel) compared to gemcitabine and nab-paclitaxel alone. Secondary endpoints also include objective response rate and overall survival. More information may be found at clinicaltrials.gov (search HALO 301 or trial identifier NCT02715804) or www.HALO301.com.

About PEGPH20
PEGPH20 is an investigational PEGylated form of Halozyme’s proprietary recombinant human hyaluronidase under clinical development for the potential systemic treatment of tumors that accumulate hyaluronan.

FDA granted orphan drug designation to PEGPH20 for treatment of pancreatic cancer and fast track for PEGPH20 in combination with gemcitabine and nab-paclitaxel for the treatment of metastatic pancreatic cancer. Additionally, the European Commission, acting on the recommendation from the Committee for Orphan Medicinal Products of the European Medicines Agency, designated investigational drug PEGPH20 an orphan medicinal product for the treatment of pancreatic cancer.

On June 04, 2016 Five Prime Therapeutics, Inc. (Nasdaq:FPRX), a clinical-stage biotechnology company focused on discovering and developing innovative immuno-oncology protein therapeutics, reported that updated data from the ongoing Phase 1b trial of FP-1039/GSK3052230 (hereafter FP-1039) in mesothelioma patients were reported today in a poster presentation at the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago (Press release, Five Prime Therapeutics, JUN 4, 2016, View Source [SID:1234512998]). Dr. Jose Trigo from the Hospital Universitario Virgen de la Victoria, Málaga, Spain, presented the poster, titled Multi-arm, open-label Phase 1b study of FP-1039/GSK3052230 with chemotherapy in malignant pleural mesothelioma (MPM). The poster is available on the Five Prime website: View Source

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The mesothelioma arm of the open-label Phase 1b trial evaluated weekly infusions of FP-1039, an FGF ligand trap, in combination with 1st-line pemetrexed and cisplatin in patients with untreated, unresectable MPM. Following the dose escalation portion of the trial, 15 mg/kg of FP-1039 was identified as the maximum tolerated dose (MTD) and established as the dose for expansion in patients with MPM. The primary study endpoints are safety and response rates, with Progression Free Survival (PFS), duration of response and translational measures as secondary endpoints. The poster includes data from 34 MPM patients who had received doses of FP-1039 as of the April 18, 2016 data cut-off and 18 patients were continuing on the trial at that time point.

Safety Data

The most common adverse events (AEs; all grades) observed were: nausea (53%), decreased appetite (41%) and fatigue (35%)
The vast majority of events were Grades 1-2
Three dose-limiting toxicities (DLTs) were reported at the 20 mg/kg dose (Grade 5 bowel perforation/ischemia, Grade 3 elevated creatinine level and Grade 3 infusion reaction) whereas no DLTs were reported at 15 mg/kg, and thus maximum tolerated dose (MTD) was established at 15 mg/kg
Toxicities associated with small-molecule FGFR inhibitors, such as hyperphosphatemia, retinal detachment and nailbed changes, have not been observed.
Efficacy Data
In the 18 patients evaluable as of April 18, 2016 who had received FP-1039 doses at or below the 15 mg/kg MTD:

Preliminary Objective Response Rate (ORR) was 39%, with a Disease Control Rate (DCR) of 100%, evaluated per mRECIST 1.1
7 confirmed Partial Responses (PRs) and 11 Stable Disease (SD)
Evaluable patients are defined as patients who enrolled at least 42 days (2 cycles) prior to the cutoff date, which was also the minimum time duration utilized in the calculation of DCR
Median Progression Free Survival (PFS) was 6.8 months, though the data are still maturing.
More than 50% (19 out of 34 dosed) of mesothelioma patients are still on trial
"The data continue to evolve and we are hopeful that FP-1039 will be shown to have potential benefit for patients with mesothelioma. Several mesothelioma patients were still on study at the time of the data cut off, so we will continue to follow their progress," said Lewis T. "Rusty" Williams, M.D., Ph.D., president and chief executive officer of Five Prime. "We are currently working with GSK to complete the trial and will be monitoring the quality and durability of patient responses and evaluating drug supply, manufacturing and other considerations as we determine the future plans for FP-1039."

About FP-1039
FP-1039 is a protein drug designed to intervene in FGF signaling. As a ligand trap, FP-1039 binds to FGF ligands circulating in the extracellular space (such as FGF2), preventing these signaling proteins from reaching FGFR1 on the surface of tumor cells. Treatment with FP-1039 treatment has not been shown to cause hyperphosphatemia, a side effect seen with small molecule inhibitors of FGF receptors, which block the activity of both cancer-associated FGFs and FGF-23. GlaxoSmithKline (GSK) is completing the ongoing Phase 1b trial in malignant pleural mesothelioma and will transfer its development and commercialization rights for FP-1039 back to Five Prime upon completion.

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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"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:
View Source

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 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."

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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.