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Jounce Therapeutics Presents Preliminary Efficacy Data from Ongoing Phase 1/2 ICONIC Trial of JTX-2011 in Patients with Advanced Cancers

On June 2, 2018 Jounce Therapeutics, Inc. (NASDAQ:JNCE), a clinical-stage company focused on the discovery and development of novel cancer immunotherapies and predictive biomarkers, reported that its preliminary data from its ongoing Phase 1/2 ICONIC trial, an adaptive design, open-label trial evaluating JTX-2011 alone and in combination with nivolumab in patients with advanced solid tumors (Press release, Jounce Therapeutics, JUN 2, 2018, View Source;p=RssLanding&cat=news&id=2352867 [SID1234527089]). Safety and preliminary clinical activity data from all evaluable patients across multiple tumor types will be presented in an oral presentation today, Saturday, June 2, 2018 at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, IL.

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"We are encouraged by the early signal of clinical activity in heavily pre-treated patients, accompanied by an ICOS pharmacodynamic biomarker. We believe that this biomarker may help guide further development of JTX-2011," said Elizabeth Trehu, M.D., chief medical officer of Jounce Therapeutics. "Importantly, JTX-2011 continues to be safe and well-tolerated both as a single agent and in combination with nivolumab. We look forward to continuing clinical evaluation of JTX-2011, including initiation of new combination dose escalation cohorts within the ICONIC trial of JTX-2011."

The ICONIC study (ICOS AgONist Antibody for Immunotherapy in Cancer Patients) is an open label, dose escalation and expansion clinical study of JTX-2011 alone and in combination with a fixed dose of nivolumab in patients with advanced solid tumors. Patients were heavily pre-treated with approximately 65 percent having received 3 or more prior therapies (i.e. 4th line or greater); approximately 65 percent discontinued during the first three cycles. The adaptive design includes Parts A and B (Phase 1), and C and D (Phase 2), with the Phase 2 cohorts enriched for high ICOS expression. The data presented today include preliminary efficacy data from all evaluable patients as of an April 4, 2018 cut-off date. The Phase 1 portion of ICONIC was a dose escalation study to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D). The patients in Phase 2 received JTX-2011 0.3 mg/kg every 3 weeks alone or in combination with nivolumab 240 mg every 3 weeks. Preliminary efficacy evaluation included tumor reductions and RECIST (response evaluation criteria in solid tumors) responses.

Summary of JTX-2011 ICONIC Data

Safety

JTX-2011 was well tolerated alone and in combination with nivolumab 240 mg every 3 weeks. The overall safety profile observed was consistent with previously reported data from the Phase 1 portion of the ICONIC trial.
Clinical Activity

Gastric Cancer

A RECIST partial response (PR) with JTX-2011 monotherapy was observed in 1 of 8 Phase 2 patients (7 PD-1 inhibitor naïve, including PR), ongoing at 8.5+ months.
Two RECIST PRs with JTX-2011 plus nivolumab were observed in 1 of 4 Phase 1 patients (all PD-1 inhibitor naïve) and 1 of 28 Phase 2 patients (22 PD-1 inhibitor naïve, including PR), ongoing at 11+ and 4+ months, respectively.
Disease control(1) was observed in 10 of 28 and tumor reductions were observed in 8 of 28 Phase 2 patients treated with JTX-2011 plus nivolumab, including both PD-1 inhibitor naïve and PD-1 inhibitor failures.
Triple Negative Breast Cancer (TNBC)

A RECIST PR with JTX-2011 plus nivolumab was observed in 1 of 17 Phase 2 patients (16 PD-1 inhibitor naïve, including PR), ongoing at 4+ months.
Disease control was observed in 3 of 17 and tumor reductions were observed in 2 of 17 Phase 2 patients treated with JTX-2011 plus nivolumab, all PD-1 inhibitor naïve.
Head and neck squamous cell cancer (HNSCC) PD-1 inhibitor failures

Disease control was observed in 2 of 16 and tumor reductions were observed in 1 of 16 Phase 2 patients treated with JTX-2011 plus nivolumab, all PD-1 inhibitor failures, of whom over 50 percent were refractory(2) to prior PD-1 inhibitors.
Non-small cell lung cancer (NSCLC) PD-1 inhibitor failures

Disease control was observed in 7 of 12 and tumor reductions were observed in 4 of 12 Phase 2 patients treated with JTX-2011 plus nivolumab, all PD-1 inhibitor failures.
(1) Disease control= confirmed PR + SD ≥ 9 weeks
(2) Refractory= best response to prior PD-1 inhibitor was progressive disease

Biomarkers

In a preliminary analysis of evaluable fresh pre-treatment biopsies, rates of disease control and tumor reduction appear higher in subjects with high ICOS scores.
An ICOS pharmacodynamic biomarker (emergence of peripheral blood ICOS high CD4 T cell population) appears to associate with anti-tumor activity.
Present in 7 of 7 subjects with target lesion PRs
Absent in 10 of 10 subjects with progressive disease
Based on preliminary signals of clinical activity associated with an ICOS pharmacodynamic biomarker, Jounce is advancing clinical evaluation of JTX-2011. The next steps for the program include continuing to evaluate the ongoing data and the initiation of two new dose escalation cohorts within the ICONIC trial of JTX-2011, one in combination with ipilimumab and one in combination with pembrolizumab. The new ipilimumab combination cohort may enable Jounce to explore a new combination mechanism that is supported by clinical and pre-clinical research. Exploration with pembrolizumab at its approved q3w dose and schedule may allow the Company to evaluate JTX-2011in combination with a PD-1 inhibitor in earlier lines of therapy.

"We look forward to evaluating the new additional combinations with JTX-2011. From our founding science, the platform we have built, and the team we have in place, we believe we are well positioned to optimize the development of JTX-2011," said Richard Murray, Ph.D., chief executive officer and president of Jounce Therapeutics. "We are grateful to all of the patients who have participated in our trial, their families, our investigators and their study teams. This was a complex biomarker heavy trial that was well executed by the Jounce team."

ICONIC Enrollment Status
Phase 1 has completed enrollment and Phase 2 is nearing completion of enrollment. Given the pace of enrollment of the combination cohorts in gastric cancer, TNBC, HNSCC, NSCLC and the overall quantity of the data collected, Jounce made the decision to stop recruitment of other solid tumors and of the more slowly enrolling monotherapy and melanoma combination cohorts.

Jounce Therapeutics to Host Event and Webcast
Jounce Therapeutics will host an investor and analyst event beginning at 6:30 p.m. CT (7:30 p.m. ET) with a live webcasted presentation beginning at 7:00 p.m. CT (8:00 p.m. ET), on Monday, June 4, 2018. To access the live webcast, please visit the "Events & Presentations" page in the Investors and Media section of the company’s website at www.jouncetx.com. The webcast will be archived and made available for replay on the company’s website approximately two hours after the call and will be available for 30 days thereafter.

About JTX-2011
Jounce’s lead product candidate, JTX-2011, is a monoclonal antibody that binds to and activates ICOS, the Inducible T cell COStimulator, a protein on the surface of certain T cells. Preclinical data support that JTX-2011 may have a dual mechanism of action that stimulates anti-tumor T effector cells, and also reduces the immunosuppressive T regulatory cells in the tumor microenvironment. The company is developing JTX-2011 to treat solid tumors as a single agent and in combination with other therapies.

Phase III IMpower131 study showed Tecentriq(atezolizumab) plus chemotherapy (carboplatin and Abraxane) reduced the risk of disease worsening or death for people with advanced squamous non-small cell lung cancer

On June 2, 2018 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that results from the Phase III IMpower131 study showed Tecentriq (atezolizumab) plus chemotherapy (carboplatin and Abraxane [albumin-bound paclitaxel; nab-paclitaxel]) reduced the risk of disease worsening or death (progression-free survival; PFS) by 29 percent compared with chemotherapy (carboplatin and nab-paclitaxel) alone in the initial (first-line) treatment of people with advanced squamous non-small cell lung cancer (NSCLC) (median PFS=6.3 vs. 5.6 months; hazard ratio [HR]=0.71, 95% CI: 0.60, 0.85, p=0.0001) (Press release, Hoffmann-La Roche, JUN 2, 2018, View Source [SID1234527077]).1 The 12-month PFS rate was doubled for people who received the Tecentriq combination (24.7 percent) compared to those who received chemotherapy alone (12.0 percent). A statistically significant overall survival (OS) benefit was not observed at the interim analysis, and the study will continue as planned. The safety profile of the Tecentriq plus chemotherapy combination was consistent with the safety profiles of the individual medicines, and no new safety signals were identified with the combination.

"The IMpower131 data further inform our understanding of this difficult-to-treat type of lung cancer and will continue to as we evaluate additional outcomes from this study," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "IMpower131 is one of eight Phase III trials from our extensive research programme evaluating Tecentriq alone or in combination with other medicines in different types of lung cancer."

Data will be featured in the official American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting press programme on Saturday, 2 June, 2018, at 08:00 am CDT. The oral data presentation will be on Monday, 4 June, 2018, at 15:00–15:12 pm CDT (Abstract LBA9000).

About the IMpower131 study
IMpower131 is a Phase III, open-label, multicentre, randomised study evaluating the efficacy and safety of Tecentriq in combination with carboplatin and nab-paclitaxel or Tecentriq in combination with carboplatin and paclitaxel versus chemotherapy (carboplatin and nab-paclitaxel) alone in people with stage IV squamous-cell NSCLC who have not been previously treated with chemotherapy. The study enrolled 1,021 people who were randomised equally (1:1:1) to receive:

Tecentriq plus carboplatin and paclitaxel (Arm A), or
Tecentriq plus carboplatin and nab-paclitaxel (Arm B), or
Carboplatin and nab-paclitaxel (Arm C, control arm)
During the treatment-induction phase, people in Arm A received four or six cycles of Tecentriq plus carboplatin and paclitaxel, given on day one of each 21-day cycle. This was followed by maintenance therapy with Tecentriq every three weeks until progression of the cancer, or for as long as clinical benefit was observed.

During the treatment-induction phase, people in Arm B received four or six cycles of Tecentriq, carboplatin and nab-paclitaxel. Tecentriq and carboplatin were administered on day one of each 21-day cycle. Nab-paclitaxel was administered on days one, eight and 15 of each 21-day cycle. This was followed by maintenance therapy with Tecentriq every three weeks until progression of the cancer, or for as long as clinical benefit was observed.

During the treatment-induction phase, people in Arm C received four or six cycles of carboplatin and nab-paclitaxel. Carboplatin was administered on day one of each 21-day cycle, and nab-paclitaxel was administered on days one, eight and 15 of each 21-day cycle. In the maintenance phase, participants received best supportive care.

The co-primary endpoints were:

PFS as determined by the investigator using RECIST v1.1 in the intention-to-treat (ITT) population (Arm B vs. Arm C)
OS in the ITT population (Arm B vs. Arm C)
Key secondary endpoints were:

PFS as determined by the investigator using RECIST v1.1 in the Tumour Cell (TC) 2/3 or Tumour-Infiltrating Immune Cell (IC) 2/3 population
PFS as determined by the investigator using RECIST v1.1 in the TC1/2/3 or IC1/2/3 population
OS in the TC2/3 or IC2/3 population
OS in the TC1/2/3 or IC1/2/3 population
Percentage of participants with objective response (OR) as determined by the investigator using RECIST v1.1 in the ITT population
Duration of response (DoR) as determined by the investigator using RECIST v1.1 in the ITT population
IMpower131 met its PFS co-primary endpoint per study protocol. This analysis of IMpower131 evaluated Arm B vs. Arm C. Due to pre-specified statistical testing hierarchy, Arm A vs Arm C has not been formally tested yet. As per the statistical analysis plan, Arm B (Tecentriq plus carboplatin and nab-paclitaxel) must demonstrate a statistically significant OS result vs. Arm C (carboplatin and nab-paclitaxel), before an analysis between Arm A (Tecentriq plus carboplatin and paclitaxel) and Arm C can be made for PFS and OS.

A summary of the IMpower131 results are included below:

The safety profile of the Tecentriq plus chemotherapy combination was consistent with the safety profiles of the individual medicines, and no new safety signals were identified with the combination. Serious adverse events related to treatment were observed in 20 percent of people who received Tecentriq plus chemotherapy compared to 10 percent of those who received chemotherapy alone.

About NSCLC
Lung cancer is the leading cause of cancer death globally.2 Each year 1.59 million people die as a result of the disease; this translates into more than 4,350 deaths worldwide every day.3 Lung cancer can be broadly divided into two major types: NSCLC and small cell lung cancer. NSCLC is the most prevalent type, accounting for around 85% of all cases.3 NSCLC comprises non-squamous and squamous-cell lung cancer, the squamous form of which is characterised by flat cells covering the airway surface when viewed under a microscope. The squamous form tends to grow near the centre of the lung, and accounts for approximately 25-30% of all NSCLC cases.4

About Tecentriq (atezolizumab)
Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1 expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the activation of T cells. Tecentriq Q has the potential to be used as a foundational combination partner with cancer immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers.

Currently, Roche has eight Phase III lung cancer studies underway, evaluating Tecentriq alone or in combination with other medicines.

Tecentriq is already approved in the European Union, United States and more than 70 countries for people with previously treated metastatic NSCLC and for people with locally advanced or metastatic urothelial cancer (mUC) who are not eligible for cisplatin chemotherapy, or who have had disease progression during or following platinum-containing therapy.

Abraxane is a registered trademark of Abraxis Bioscience, LLC, a wholly owned subsidiary of Celgene Corporation.

Deciphera Pharmaceuticals Reports Updated Interim Phase 1 Clinical Study Results with DCC-2618 at The 2018 American Society of Clinical Oncology Annual Meeting (ASCO) and Provides Additional Clinical and Regulatory Updates on DCC-2618

On June 2, 2018 Deciphera Pharmaceuticals, Inc. (NASDAQ:DCPH), a clinical-stage biopharmaceutical company focused on addressing key mechanisms of tumor drug resistance, reported the presentation today of updated data from its ongoing Phase 1 clinical trial of DCC-2618, the company’s broad-spectrum KIT and PDGFRα inhibitor, in patients with gastrointestinal stromal tumors (GIST) at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2018, in Chicago, Illinois and provided additional clinical and regulatory updates on DCC-2618 (Press release, Deciphera Pharmaceuticals, JUN 2, 2018, View Source [SID1234527070]).

Suzanne George, M.D. Assistant Professor of Medicine, Harvard Medical School and Clinical Director, Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute presented the poster titled "Mutational Profile of Drug Resistant GIST Patients Enrolled in the Phase 1 Study of DCC-2618". In addition to describing the mutational profile of KIT in GIST patients, the poster includes details of locally-read Objective Response Rates (ORR) and Disease Control Rates (DCR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) in second, third, and fourth and fourth line plus GIST patients that received DCC-2618 at doses of ≥100mg daily for at least one 28-day cycle prior to February 2, 2018:

The combined 24% ORR and 80% 3-month DCR in second and third line patients receiving DCC-2618 at doses of ≥100mg per day exceeds previously published results of registrational trials for the currently approved therapies for second line (sunitinib) and third line (regorafenib), which have reported ORRs of 7.0% and 4.5%, respectively, and levels of disease control of 60% and 53%, respectively.

"The preliminary data presented today on DCC-2618’s activity in second and third line GIST patients is very encouraging and supports the planned initiation later this year of our Phase 3 trial, INTRIGUE, in second line GIST patients," said Michael D. Taylor, Ph.D., President and Chief Executive Officer of Deciphera. "The mutational profiling data across second, third and fourth line GIST patients observed in the Phase 1 study also demonstrates the need for the broadest spectrum of KIT inhibition in all GIST patients who previously received imatinib."

"We are very pleased with the results presented today demonstrating DCC-2618’s potential to provide improved clinical benefit for not only heavily pre-treated patients, but also for second and third line GIST patients," said Oliver Rosen, M.D. Chief Medical Officer of Deciphera. "Combined with the tolerability data presented at AACR (Free AACR Whitepaper) in April 2018, these results demonstrate the potential of DCC-2618 as an effective and well tolerated therapy for a wide range of GIST patients."

Highlights from the poster presentation include:

Initial Objective Response Rates and Disease Control Rates with DCC-2618 at Doses of ≥100mg Daily in Second and Third Line GIST Patients Exceed Previously Published Results of Registrational Trials for Currently Approved Therapies, as well as the Results Observed in Heavily Pre-Treated GIST Patients Receiving DCC-2618:
24% ORR with DCC-2618 observed to date in second and third line GIST patients is higher than that reported for sunitinib in second line patients (7.0%) or regorafenib in third line patients (4.5%).
These interim results show improved ORR and 3-month DCR in second line GIST patients treated with DCC-2618 compared to fourth and fourth line plus GIST patients treated with DCC-2618.
Mutational Profiling Data Across Second, Third and Fourth Line GIST Patients Demonstrates the Breadth of KIT Mutations in GIST and the Ability of DCC-2618 to Reduce KIT Mutant Allele Frequency (MAF):
Resistance mutations in KIT in exons 13, 14, 17 and 18, or a combination thereof, occurs in second, third and, fourth and fourth line plus patients.
The KIT mutational profile in both tumors and plasma at baseline in GIST patient supports the need for a broad-spectrum KIT inhibitor in all post-imatinib lines of therapy.
57 of 73 patients (78%) receiving DCC-2618 at doses of ≥100 mg daily demonstrated reductions in KIT MAF of more than 50%.
In addition, the company is providing the following clinical and regulatory updates on DCC-2618:

Planned Initiation of a Phase 3 Trial in Second Line GIST Patients in 2018
Preliminary efficacy results in second line patients together with recently presented tolerability data at the recommended phase 2 dose (RP2D) of 150mg QD support the planned, randomized Phase 3 trial, INTRIGUE, in second line GIST.
Following discussions with regulatory authorities in the United States and in Europe, the company has designed INTRIGUE as a randomized, multicenter, open-label, Phase 3 trial in second line GIST. This registration study is expected to enroll approximately 350 patients who will be randomized 1:1 to either DCC-2618 or sunitinib, the current standard of care in second line; with median progression free survival as the primary endpoint.
Interim Results with DCC-2618 at Doses of ≥100mg Daily Demonstrate Robust Clinical Activity in Heavily Pretreated GIST Patients, Including Patients Previously Treated with the Investigational Agent avapritinib (BLU-285):
10 patients with KIT-driven GIST who previously received avapritinib were enrolled and treated with DCC-2618 as of January 31, 2018.
6 out of 10 (60%) of these patients achieved stable disease as best response by RECIST during treatment with DCC-2618. In addition, one patient achieved stable disease following intra-patient dose escalation to 150mg BID.
5 out of 10 (50%) of these patients were on study as of April 18, 2018.
3 out of 10 (30%) of these patients received DCC-2618 for more than six months. Two of these patients achieved continued stable disease and remain on study as of April 18, 2018. The third patient with progressive disease was dose escalated and was reported as off study as of April 18, 2018.
A copy of the poster presentation will be available on the Science section of the Deciphera website under "Presentations and Publications" at www.deciphera.com.

About DCC-2618

DCC-2618 is a KIT and PDGFRα kinase switch control inhibitor in clinical development for the treatment of KIT and/or PDGFRα-driven cancers, including gastrointestinal stromal tumors, or GIST, systemic mastocytosis, or SM, and glioblastoma multiforme. DCC-2618 was specifically designed to improve the treatment of GIST patients by inhibiting a broad spectrum of mutations in KIT and PDGFRα. DCC-2618 is a KIT and PDGFRα inhibitor that blocks initiating and secondary KIT mutations in exons 9, 11, 13, 14, 17, and 18, involved in GIST as well as the primary D816V exon 17 mutation involved in SM. DCC-2618 also inhibits primary PDGFRα mutations in exons 12, 14 and 18, including the exon 18 D842V mutation, involved in a subset of GIST.

Celldex Presents Promising Data from Phase 1/2 Study of Varlilumab and Opdivo® at 2018 ASCO Annual Meeting

On June 2, 2018 Celldex Therapeutics, Inc. (NASDAQ:CLDX) today presented two programs at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago (Press release, Celldex Therapeutics, JUN 2, 2018, View Source [SID1234527065]). Data from the Phase 1/2 study of Celldex’s varlilumab, a CD27 targeting investigational immune-activating antibody, and Bristol-Myers Squibb’s Opdivo (nivolumab), an anti-PD1 immunotherapy, for patients with ovarian cancer and colorectal cancer, were presented in an oral session by Rachel E. Sanborn, M.D., Co-director of the Providence Thoracic Oncology Program and Phase 1 Clinical Trials Program, at the Earle A. Chiles Research Institute, Providence Cancer Institute, in Portland, Ore. In addition, an overview of the Phase 2 study of the anti-ErbB3 antibody CDX-3379 in combination with Erbitux in advanced head and neck squamous cell cancer was presented in a "clinical trials in progress" poster session.

"The data presented today continue to support that varlilumab holds considerable potential as an immune activator," said Dr. Sanborn. "This was particularly noteworthy in ovarian cancer where the combination with the anti-PD1 monoclonal antibody, Opdivo, turned "immune-cold" tumors "hot," which in turn correlated with improved clinical outcomes, including improved response rate and progression-free survival in these patients."

"Moving forward, we believe more work needs to be done to identify synergistic combinations and patient populations that have the best chance of responding to varlilumab treatment," said Tibor Keler, Ph.D., Executive Vice President and Chief Scientific Officer of Celldex Therapeutics. "We are continuing to explore these opportunities through inclusion in our ongoing Phase 1 study of CDX-1140, our CD40 agonist antibody, and several investigator-initiated studies."

"We also continue to enroll patients into our ongoing Phase 2 study of CDX-3379 in combination with Erbitux in patients with HPV negative, Erbitux-resistant, advanced head and neck squamous cell carcinoma. We look forward to completing enrollment to the first stage of this study in the third quarter of 2018 and are exploring other potential opportunities in indications where ErbB3 is believed to play a role," concluded Dr. Keler.

ASCO Highlights

Varlilumab

Varlilumab was featured in an oral presentation that highlighted the ongoing Phase 2 study of varlilumab in combination with Opdivo. The Phase 1/2 study includes cohorts in ovarian cancer, colorectal cancer, head and neck squamous cell carcinoma, renal cell carcinoma and glioblastoma, with data from ovarian cancer (n=66) and colorectal cancer (n=42) patients included in the presentation today. The majority of patients enrolled in the study had baseline tumors that were mostly "cold" (PD-L1 negative or low, and low tumor-infiltrating lymphocyte [TIL] levels) with low expectation of responding to checkpoint inhibition therapy. The combination was well tolerated at all varlilumab dose levels tested.

Results in Ovarian Cancer Experience: n=66, 8 patients in Phase 1; 58 patients in Phase 2; median of three prior lines of therapy; 91% had Stage IV disease; 66% with PD-L1 negative tumors; multiple varlilumab dosing regimens evaluated. Detailed information by dosing cohort is included in the presentation and is available on the Celldex website.

Overall response rate: 14% (n=9) across 64 response-evaluable patients (7 confirmed, 2 unconfirmed)
Response rate by PD-L1 status:
PD-L1 positive: 20% (n=4 of 20; 3 confirmed, 1 unconfirmed)
PD-L1 negative: 14% (n=5 of 37; 4 confirmed, 1 unconfirmed)
Disease control rate (DCR), defined as best response of stable disease or better for greater than or equal to three months, was 38% (n=24 of 64). As of the cut-off for analysis, five patients continued on treatment.
For patients with tumor samples available, most patients experienced increases in tumor expression of PD-L1 (n=14 of 23; 61%) and CD8+ TIL levels (n=14 of 24; 58%). These increases were associated with improved clinical outcome, including improved progression-free survival (PFS) and response rate.

Results in Colorectal Cancer Experience: n=42; 21 patients in Phase 1; 21 patients in Phase 2; median of four prior lines of therapy; 100% had Stage IV disease; 87% had PD-L1 negative tumors; one patient was MSI-high and 21 patients were MSI-low/mismatch repair (MMR) proficient; MSI status for the remaining 20 patients was unknown.

One patient with PD-L1 negative, MSI-high disease experienced a confirmed partial response in the Phase 2 study portion and continues on treatment. Of note, a patient with PD-L1 negative disease, initially considered MMR proficient as determined by standard screening laboratory analysis, achieved a near complete response in the Phase 1 portion of the study, which now continues at 35 months. As part of this study, an additional molecular analysis was conducted on this patient’s tumor. The tumor had a high mutational burden and mutations in genes regulating DNA repair, which together likely contributed to the response. DCR was 20% (8/41).
CDX-3379

CDX-3379 was featured in a "clinical trials in progress" poster presentation, available on the Celldex website, that highlighted the ongoing Phase 2 study of CDX-3379, a human monoclonal antibody designed to block the activity of ErbB3 (HER3), in combination with Erbitux in patients with human papillomavirus (HPV) negative, Erbitux-resistant, advanced head and neck squamous cell carcinoma. The proposed mechanism of action for CDX-3379 sets it apart from other drugs in development in this class due to its ability to block both ligand-independent and ligand-dependent ErbB3 signaling by binding to a unique epitope. It has a favorable pharmacologic profile, including a longer half-life and slower clearance relative to other drug candidates in this class. The multicenter, open-label, Simon two-stage design study is expected to enroll approximately 27 patients (Stage 1=13; Stage 2=14). The primary objective of the study is objective response rate. Secondary objectives include assessments of clinical benefit response, duration of response, progression-free survival and overall survival, and safety and pharmacokinetics associated with the combination. Four clinical trial sites are currently open to enrollment, and Celldex is targeting to complete enrollment to the first stage of the study by the end of the third quarter of 2018. The Company continues to explore potential other opportunities in additional indications where ErbB3 is believed to play a role.

Preliminary Data for NKTR-214 in Combination with Opdivo (nivolumab) for Patients with Stage IV Metastatic Melanoma, Renal Cell Carcinoma, and Urothelial Cancers Presented at ASCO 2018

On June 2 Nektar Therapeutics (Nasdaq: NKTR) and Bristol-Myers Squibb (NYSE: BMY) reported presentation of preliminary data from the ongoing PIVOT Phase 1/2 Study, which is evaluating the combination of Bristol-Myers Squibb’s Opdivo (nivolumab) with Nektar’s investigational medicine, NKTR-214 (Press release, Bristol-Myers Squibb, JUN 2, 2018, View Source [SID1234527062]). The preliminary results presented at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) reported safety, efficacy and biomarker data for patients enrolled in the Phase 1 dose-escalation stage of the study and for the first patients consecutively enrolled in select dose expansion cohorts in Phase 2. Data were presented today in an oral presentation (Oral Abstract Session: Developmental Therapeutics—Immunotherapy, Abstract #3006, 5:00 p.m. – 5:15 p.m. CT, Hall B1).

Enrollment is ongoing in the Phase 2 stage of the PIVOT study in over 400 patients with melanoma, renal cell, urothelial, non-small cell lung and triple negative breast cancers.

Preliminary results from the ongoing PIVOT study presented today showed that pre-specified efficacy criteria were achieved in three tumor types: first-line melanoma, first-line renal cell carcinoma and first-line urothelial cancer. As a result, Nektar and Bristol-Myers Squibb will initiate a Phase 3 registrational trial in first-line advanced melanoma patients in Q3 2018, and pivotal studies are also being designed in renal cell carcinoma and urothelial cancer.

"In the Phase 1 dose-escalation and Phase 2 expansion stages of the PIVOT trial to-date, we’ve observed important responses, including activity in PD-L1 negative patients," said Mary Tagliaferri, M.D., Senior Vice President of Clinical Development and Chief Medical Officer at Nektar Therapeutics. "We look forward to advancing this combination into Phase 3."

The PIVOT study incorporates a Fleming 2-Stage Design, with efficacy targets separately pre-defined for each tumor type using a historical objective response rate (for single-agent checkpoint inhibitor).1 If the efficacy criteria at the recommended Phase 2 dose (RP2D) is met in the first stage (N1) of patients consecutively enrolled or in the second stage (N1 + N2) of patients consecutively enrolled, the combination regimen would be advanced to registrational trials in that tumor type.

Opdivo is a PD-1 immune checkpoint inhibitor designed to overcome immune suppression. NKTR-214 is an investigational immuno-stimulatory therapy designed to expand and activate specific cancer-fighting T cells and natural killer (NK) cells directly in the tumor micro-environment and increase expression of cell-surface PD-1 on these immune cells.

"Researching IL-2 pathway agonism and anti-PD-1 in combination may be a key strategy to more effectively activate an anti-tumor immune response," said Fouad Namouni, M.D., Head of Oncology Development, Bristol-Myers Squibb. "These preliminary results from PIVOT are encouraging, particularly in the PD-L1 negative population, and support our belief that that NKTR-214, a CD122 biased IL2 agonist, in combination with Opdivo can potentially expand the treatment benefits we can bring to patients with cancer."

Highlights from the oral presentation include:

Clinical Efficacy (Response measured per RECIST 1.1 for efficacy-evaluable patients (treated at the recommended Phase 2 dose and with >1 on treatment scan. Response and median time on study calculated from data cut as of May 29, 2018):

Stage IV Metastatic Treatment-Naïve 1L Melanoma Patients (Enrolled Per Fleming 2-Stage Design at RP2D):
Pre-specified efficacy criteria were met for Objective Response Rate (ORR) in Stage 1 (N1=13) with 11/13 (85%) of patients achieving either a partial response (PR) or complete response (CR). Median time on study for 28 patients in Stage 2 (N1+N2) is 4.6 months. Responses were observed in 14/28 (50%) patients (3 CR, 10 PR, 1 uPR). Amongst the 25 patients with known PD-L1 status, ORR in PD-L1 negative patients was 5/12 (42%) and in PD-L1 positive patients was 8/13 (62%). One patient with unknown PD-L1 baseline status experienced a CR.
Stage IV Metastatic Treatment-Naïve 1L Renal Cell Carcinoma Patients (Enrolled Per Fleming 2-Stage Design at RP2D):
Pre-specified efficacy criteria were met for ORR in Stage 1 (N1=11) with 7/11 (64%) of patients achieving a partial response (PR). Median time on study for 26 patients in Stage 2 (N1 + N2) is 5.6 months. Responses were observed in 12/26 (46%) patients (11 PR, 1 uPR). Amongst the 24 patients with known PD-L1 status, The ORR in PD-L1 negative patients was 9/17 (53%) and in PD-L1 positive patients was 2/7 (29%). One of two patients (50%) with unknown PD-L1 baseline status experienced a PR.
Stage IV Metastatic Treatment-Naïve 1L Urothelial Carcinoma (Enrolled Per Fleming 2-Stage Design at RP2D):
Pre-specified efficacy criteria were met for ORR in Stage 1 (N1=10) with 6/10 (60%) of patients achieving either a partial or complete response (2 uCR, 3 PR, 1 uPR). Median time on study for 10 patients in Stage 1 is 3.9 months. The ORR in PD-L1 negative patients was 3/5 (60%) and in PD-L1 positive patients was 3/5 (60%).
Biomarkers and Mechanism of Action:

Data presented show conversion of PD-L1 negative status at baseline to PD-L1 positive status at week 3 in 9/17 patients (53%). Of these previously PD-L1 negative patients, 78% achieved clinical benefit as defined by stable disease, partial response or complete response.
Clinical Safety (Safety database as of May 7, 2018):

A total of 283 patients have been treated at the RP2D. The most common treatment-related adverse events (TRAEs) were grade 1-2 flu-like symptoms (58.7%), rash (44.5%), fatigue (42.0%), and pruritus (31.4%). A total of 40/283 (14.1%) of patients experienced a Grade 3 (G3) or higher TRAE with 6/283 (2.1%) patients discontinuing treatment due to a TRAE. 10/283 (3.5%) of patients experienced a G3 or higher immune-mediated AE. There was one nivolumab-related G5 pneumonitis reported.
A copy of the full data presentation made by Dr. Diab is available on Nektar’s corporate website at View Source

Nektar and Bristol-Myers Squibb entered into a global strategic development and commercialization collaboration for NKTR-214 in February 2018. Under the collaboration, the companies will jointly develop and commercialize NKTR-214 in combination with Bristol-Myers Squibb’s nivolumab and Opdivo plus Yervoy (ipilimumab) in more than 20 indications across 9 tumor types, as well as potential combinations with other anti-cancer agents from either of the respective companies and/or third parties.

About NKTR-214

NKTR-214 preferentially binds to the CD122 receptor on the surface of cancer-fighting immune cells in order to stimulate their proliferation. In clinical and preclinical studies, treatment with NKTR-214 resulted in expansion of these cells and mobilization into the tumor micro-environment.2,3,4 NKTR-214 has an antibody-like dosing regimen similar to the existing checkpoint inhibitor class of approved medicines.

Nektar will webcast an analyst and investor event to review data presented in the oral session and new additional data from the PIVOT study on Saturday, June 2, 2018 at 6:45 p.m. CDT in Chicago, IL. PIVOT clinical investigators attending include Dr. Adi Diab, Assistant Professor, Melanoma Medical Oncology at the University of Texas MD Anderson Cancer Center, Dr. Scott N. Gettinger, Associate Professor, Medical Oncology at the Yale Cancer Center and Dr. Nizar M. Tannir, Professor, Genitourinary Medical Oncology at the University of Texas MD Anderson Cancer Center. Investors and analysts are invited to listen to a live audio webcast of the event, which will be accessible from the home page of the company’s website www.nektar.com. The webcast will also be available for replay for two weeks following the event.