On June 3, 2017 TG Therapeutics (NASDAQ:TGTX) reported positive results from its Phase 3 GENUINE trial of TG-1101 (ublituximab) plus ibrutinib in patients with previously treated high risk Chronic Lymphocytic Leukemia (CLL) (Press release, TG Therapeutics, JUN 3, 2017, View Source [SID1234519447]). Data from this trial was presented today by Dr. Jeff Sharman, Medical Director, Hematology Research, US Oncology in an oral session during the 53rd American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, IL.

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Michael S. Weiss, Executive Chairman and Chief Executive Officer of TG Therapeutics stated, "Patients with high-risk CLL have the poorest outcomes on ibrutinib and are in need of a more efficacious treatment. We believe the data presented today demonstrate that the addition of TG-1101 to ibrutinib improves patient outcomes across multiple measures." Mr. Weiss continued, "In addition to increasing the overall number of patients that responded to treatment with ibrutinib, adding TG-1101 to ibrutinib increased the number of patients with bone marrow confirmed CR’s, MRD negativity in peripheral blood, deepened nodal responses, and resulted in fewer patients progressing on therapy. Collectively, we see the consistent pattern of enhanced benefit as providing a compelling case for combining TG-1101 with ibrutinib in these hard to treat patients with high-risk CLL. We look forward to sharing these data with the FDA later this year to discuss filing for accelerated approval. We would like to thank our investigators and their patients for their participation in this important clinical trial."

Highlight’s from this presentation include the following:

Oral Presentation: Ublituximab and ibrutinib for previously treated genetically high-risk chronic lymphocytic leukemia: Results of the GENUINE Phase 3 study

This presentation includes data from the GENUINE Phase 3 trial, a multicenter, randomized trial (NCT02301156), which assessed the efficacy and safety of TG-1101 plus ibrutinib versus ibrutinib alone in patients with high risk CLL. For the trial, high-risk was defined as having any one or more of the following centrally confirmed features: 17p deletion, 11q deletion or p53 mutation. The GENUINE study was designed to demonstrate the value of adding TG-1101, a potent next generation glycoengineered anti-CD20 monoclonal antibody to ibrutinib monotherapy in high-risk CLL, and was powered to show a statistically significant improvement in ORR of 30%, with a minimal absolute detectable difference between the two arms of approximately 20%.

The trial met its primary endpoint, demonstrating a statistically significant improvement in Overall Response Rate (ORR), as assessed by blinded independent central radiology and hematology review by iwCLL (Hallek 2008) criteria, compared to ibrutinib alone in both the Intent to Treat (ITT) population (p=0.001) and Treated population (p < 0.001). Per iwCLL guidelines, all responders required confirmation of response for a minimum duration of 2 months. The ITT population includes all 126 randomized patients (64 in the TG-1101 plus ibrutinib arm and 62 in the ibrutinib alone arm) while the Treated population includes all ITT patients that received at least one dose of either study drug (59 in the TG-1101 plus ibrutinib arm and 58 in the ibrutinib alone arm).

Patient Demographics

One hundred and twenty-six (126) patients were randomized on the GENUINE Phase 3 trial. 100% of patients were high-risk and had either 17p deletion, 11q deletion or p53 mutation. Sixty-four percent (64%) of patients in the TG-1101 plus ibrutinib arm and 66% of patients in the Ibrutinib alone arm had 17p deletion and/or a p53 mutation while 36% and 34% of patients in the TG-1101 plus ibrutinib and ibrutinib alone arms, respectively, had an 11q deletion only. The median age of patients on either arm was 67 years and the median number of prior lines of therapy for either arm was 3.

Safety & Tolerability

One hundred and seventeen (117) patients were evaluable for safety (59 patients in the TG-1101 plus ibrutinib arm, and 58 patients in the ibrutinib alone arm). The combination was well tolerated and, apart from infusion related reactions, the addition of TG-1101 did not appear to alter the safety profile of ibrutinib monotherapy. Neutropenia, occurring in 9% of patients, was the most commonly reported Grade 3/4 Adverse Event (AE) in the combination arm, followed by infusion related reactions and anemia, each reported in 5% of patients. Notably, the majority of infusion related reactions (IRR) were Grade 1 or 2 in severity, with only 5% Grade 3/4 IRR observed. Median follow-up for this study was approximately 11.4 months.

Clinical Activity

Response Rates

TG-1101 plus Ibrutinib Ibrutinib P-value
Treated Population (n) n=59 n=58
Overall Response Rate (ORR) 78 % 45 % P < 0.001
Complete Response (CR) 7 % 0 % NS
MRD-Negative 19%
(n=53) * 2%
(n=53) * P < 0.01

*Patients evaluable for MRD included those enrolled > 4 months prior to data cutoff date of February 15, 2017. MRD analyzed by central lab, 7-color flow cytometry

In addition to the improvements in ORR, CR and MRD-negativity, a trend in improvement of Progression Free Survival (PFS) was observed in the combination arm of TG-1101 plus ibrutinib as compared to ibrutinib alone (Hazard Ratio = 0.559; p=NS).

ABOUT THE PHASE 3 GENUINE STUDY

The Phase 3 GENUINE study is a randomized, open label, multicenter clinical trial to evaluate the safety and efficacy of TG-1101 (ublituximab) plus ibrutinib compared to ibrutinib alone in adult patients with high-risk Chronic Lymphocytic Leukemia (CLL) who received at least one prior therapy for their disease.

The study was conducted at 160 clinical trial sites in the US and Israel and randomized 126 patients. Patients received ibrutinib orally at 420 mg once daily in both arms and in the combination arm those patients also received intravenous infusions of TG-1101 at 900 mg dosed on days 1, 8 and 15 of cycle 1 and day 1 of cycles 2-6. Patients in the combination arm who had not progressed received quarterly infusions of TG-1101 maintenance at 900 mg.

PRESENTATION DETAILS:

The above referenced presentation is now available on the Publications page, located within the Pipeline section, of the Company’s website at www.tgtherapeutics.com/publications.cfm.

On June 3, 2017 TESARO, Inc. (NASDAQ:TSRO), an oncology-focused biopharmaceutical company, reported initial data from the TOPACIO trial of niraparib plus KEYTRUDA (pembrolizumab) and results of a Phase 1 trial of TSR-042 during an investor briefing held in conjunction with the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2017 Annual Meeting (Press release, TESARO, JUN 3, 2017, View Source [SID1234519444]). The Company also provided an update on its commercial businesses in the U.S. and Europe.

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"ASCO represents an opportunity to showcase ZEJULA and the potential for it to positively impact the lives of women with recurrent ovarian cancer. Data presented earlier today during the conference further characterize the positive, durable treatment effects of ZEJULA and the clinical benefit in women who have residual disease following treatment with platinum-based chemotherapy. We are excited that the initial data from TOPACIO suggest a potential synergy between niraparib and an anti-PD-1 antibody, and look forward to evaluating this combination further in ovarian cancer and additional tumor types," said Lonnie Moulder, CEO of TESARO. "To date, there has been an overwhelmingly positive response by prescribers, patients and payors related to our U.S. launch and the potential for ZEJULA to benefit women with recurrent ovarian cancer. Our European organization has started filling orders for VARUBY in Germany, with other countries soon to follow. Pre-launch preparations are also underway to support the introduction of ZEJULA in Europe later this year, pending European Commission approval. In the U.S., demand for the oral formulation of VARUBI continues to increase and we look forward to a fourth quarter launch of VARUBI IV to extend our offering for patients who are undergoing emetogenic chemotherapy. Finally, our immuno-oncology programs are advancing at a rapid pace, led by the clinical study of TSR-042, our anti-PD-1 antibody, which we believe will form the basis for a registration of the drug in patients with MSI-H tumors, including endometrial cancer."

TOPACIO Data Demonstrate Activity in Platinum-Resistant Ovarian Cancer
TOPACIO is a Phase 1/2 clinical trial designed to evaluate the preliminary safety and efficacy of niraparib plus KEYTRUDA (pembrolizumab) in patients with recurrent, platinum-resistant ovarian cancer or triple negative breast cancer. Phase 1 of TOPACIO consisted of a dose escalation study to evaluate an oral, once-daily dose of niraparib (200 milligrams or 300 milligrams) plus 200 milligrams of pembrolizumab administered intravenously on day one of each 21-day treatment cycle. Endpoints included tolerability assessments, pharmacokinetic measures, and RECIST response rate.

In the dose escalation phase, a disease control rate of 69% was observed (9 of 13 evaluable patients), including 3 PRs and 1 CR, in patients with platinum-resistant ovarian cancer. The most common grade ≥3 adverse events included thrombocytopenia, anemia and neutropenia. At the recommended Phase 2 dose, one of seven patients experienced grade 3 thrombocytopenia and no significant overlapping toxicities were observed. A dose of 200 milligrams of niraparib once daily was selected for evaluation with pembrolizumab in Phase 2 of this study.

The first expansion cohorts of patients with platinum-resistant ovarian cancer (n=24) and triple-negative breast cancer (n=24) are now fully enrolled, and the second expansion cohorts for each tumor have been opened. Additional data from this trial are anticipated to become available during the second half of 2017.

The TOPACIO trial is being conducted in collaboration with Merck Sharp & Dohme B.V., a subsidiary of Merck & Co., Inc., which is providing support for the trial.

TSR-042 Phase 1 Results Show Anti-PD-1 Activity
The Phase 1 study of TSR-042, TESARO’s anti-PD-1 antibody, is now complete. No dose limiting toxicities were observed. Among the 21 heavily pretreated patients in Part 1 of the study, two had a partial response (PR) and five had stable disease. Adverse events were commensurate with commercially-available anti-PD-1 therapies.

Following the identification of a fixed dose and patient-centric dosing schedule, the ongoing clinical trial of TSR-042 was expanded to enroll patients with metastatic microsatellite instability-high (MSI-H) endometrial cancer who have progressed following one or two prior chemotherapy treatments. During the first 12 weeks of treatment, TSR-042 is administered once every three weeks, followed by administration every six weeks until disease progression. The intent of this study is to support a request for accelerated approval and Biologics License Application (BLA) submission to the U.S. Food and Drug Administration (FDA). The primary endpoints of this trial are overall response rate (ORR) and duration of response, and secondary endpoints include disease control rate, progression free survival (PFS), and overall survival (OS). The addition of cohorts for patients with other tumor types, including those with MSI-H tumors, is also planned. This is the first clinical development program within a broader plan that includes potential label expansion trials of TSR-042 in multiple cancers in combination with ZEJULA, TSR-022, TESARO’s anti-TIM-3 antibody, and TSR-033, TESARO’s anti-LAG-3 antibody.

Niraparib Data Presentations at ASCO (Free ASCO Whitepaper) Demonstrate Positive, Durable Treatment Effect
Three posters describing additional data analyses from the Phase 3 ENGOT-OV16/NOVA trial of niraparib were presented today during the ASCO (Free ASCO Whitepaper) Annual Meeting.

An analysis was performed to assess PFS and safety in patients who enrolled in the NOVA trial after a PR to their last platinum-based chemotherapy. Approximately 50% of all patients who enrolled in this trial entered with a PR, and results demonstrated that niraparib treatment provided significant benefit to these patients, with a treatment effect similar to that observed in the overall study population in both the gBRCAmut cohort (HR=0.24 for patients with a PR vs. HR=0.27 for all patients) and non-gBRCAmut cohort (HR=0.35 for patients with a PR and HR=0.45 for all patients). The safety profile of niraparib-treated patients with a PR was similar to that of the overall study population.

An assessment of platinum resistance status of patients in the NOVA trial was performed to better understand the population of patients that could benefit from treatment with niraparib. Approximately 50% of the patients in the placebo arm of this trial were found to have platinum-resistant disease following their last platinum-based therapy, as defined by progressive disease occurring less than six months following the last dose of chemotherapy. These findings suggest that approximately half of the total NOVA study population had disease that would have been considered platinum-resistant when they began maintenance treatment during the trial. The results of NOVA demonstrate that patients who had developed platinum-resistant disease after their last round of chemotherapy experienced benefit from niraparib maintenance.

Additional analyses of NOVA assessed the longer-term efficacy of niraparib. Across both the gBRCAmut and non-gBRCAmut cohorts, treatment with niraparib increased the probability of PFS at 12, 18 and 24 months from randomization vs. placebo, as demonstrated by Kaplan-Meier estimates. The similarity in results for PFS2 minus PFS1 between niraparib and placebo suggests that niraparib had no decremental effect on the benefit of subsequent therapy.
Robust Demand for ZEJULA Continues
The U.S. launch of ZEJULA is off to a strong start, with more than 800 new patient starts since approval and prescriptions written by over 600 physicians. TESARO introduced ZEJULA in late April, following U.S. FDA approval for use as a maintenance treatment for women with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response (CR or PR) to platinum-based chemotherapy. ZEJULA is the only PARP inhibitor to have demonstrated efficacy in patients without BRCA mutations in a randomized, Phase 3 trial and is the only PARP inhibitor to be approved by the FDA that does not require patient selection with a biomarker test. Pre-launch preparations continue in support of a European launch of ZEJULA by year-end 2017, pending European Commission approval. The niraparib early access program, or EAP, has already enrolled a number of patients in Europe, and more patients are anticipated to enter the program.

VARUBY Launches Ongoing in Europe; VARUBI IV PDUFA Date Established in the U.S.
Following the approval of VARUBY (oral formulation) by the European Commission for the prevention of delayed nausea and vomiting associated with highly and moderately emetogenic cancer chemotherapy in adults, VARUBY is now available in Germany. In the U.S., the FDA has accepted the Company’s NDA re-submission for rolapitant IV and classified it as a Class 2 resubmission with a Prescription Drug User Fee Act (PDUFA) action date of October 25, 2017. TESARO is committed to bringing the intravenous formulation of VARUBI to physicians and patients to enable additional flexibility and choice of antiemetic regimens.

About ZEJULA (niraparib)
ZEJULA (niraparib) is an oral, once-daily poly(ADP-ribose) polymerase (PARP) 1/2 inhibitor that is indicated in the U.S. for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. In preclinical studies, ZEJULA concentrates in the tumor relative to plasma, delivering greater than 90% durable inhibition of PARP 1/2 and a persistent antitumor effect.

ZEJULA (niraparib) Select Important Safety Information
Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML) was reported in patients treated with ZEJULA in all clinical studies. Discontinue ZEJULA if MDS/AML is confirmed. Hematologic adverse reactions (thrombocytopenia, anemia and neutropenia) have been reported in patients treated with ZEJULA. Do not start ZEJULA until patients have recovered from hematological toxicity caused by previous chemotherapy (≤ Grade 1). Monitor complete blood counts weekly for the first month, monthly for the next 11 months of treatment, and periodically after this time.

Hypertension and hypertensive crisis have been reported in patients treated with ZEJULA. Monitor blood pressure and heart rate monthly for the first year and periodically thereafter during treatment with ZEJULA. Closely monitor patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.

Based on its mechanism of action, ZEJULA can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for six months after receiving the final dose. Because of the potential for serious adverse reactions in breastfed infants from ZEJULA, advise a lactating woman not to breastfeed during treatment with ZEJULA and for one month after receiving the final dose.

In clinical studies, the most common adverse reactions included: thrombocytopenia, anemia, neutropenia, nausea, constipation, vomiting, abdominal pain/distension, mucositis/stomatitis, diarrhea, fatigue/asthenia, decreased appetite, headache, insomnia, nasopharyngitis, dyspnea, rash and hypertension.

Please see full Prescribing Information for additional Safety Information at www.zejula.com.

About VARUBI (rolapitant)
VARUBI is a substance P/neurokinin-1 (NK-1) receptor antagonist indicated in combination with other antiemetic agents in adults for the prevention of delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy. NK-1 receptors are highly concentrated in the brain and bind neurokinin substance P. Activation of NK-1 receptors plays a central role in nausea and vomiting induced by emetogenic stimuli, including certain cancer chemotherapies. A Positron Emission Tomography (PET) study with rolapitant in normal, healthy volunteers demonstrated that rolapitant crosses the blood brain barrier and occupies brain NK-1 receptors at high levels for up to 120 hours. VARUBI has a half-life of approximately seven days, which may contribute to the ability of a single dose of VARUBI to cover the entire delayed CINV Phase (25-120 hours). VARUBI is contraindicated in patients receiving thioridazine, a CYP2D6 substrate. The inhibitory effect of a single dose of VARUBI on CYP2D6 lasts at least seven days and may last longer. Avoid use of pimozide; monitor for adverse events if concomitant use with other CYP2D6 substrates with a narrow therapeutic index cannot be avoided. Please see full prescribing information, including additional important safety information, available at View Source

About TSR-042
TSR-042 is a monoclonal antibody targeting PD-1 and was developed as part of the collaboration between TESARO and AnaptysBio, Inc. This collaboration was initiated in March of 2014, and is focused on the development of monospecific antibody drugs targeting PD-1, TIM-3 (TSR-022), and LAG-3 (TSR-033), in addition to a bi-specific antibody drug candidate targeting PD-1/LAG-3.

About Endometrial Cancer
Endometrial cancer is the most common type of uterine cancer, accounting for more than 95 percent of cases. Endometrial cancer develops in the lining of the uterus, called the endometrium. The annual number of new cases of endometrial cancer is estimated at 325,000 worldwide. The most common histologic form is endometrioid adenocarcinoma originating in the glandular tissue, which represents about 75-80% of diagnosed cases. In 2017, SEER1 estimates 61,380 patients will be diagnosed with endometrial cancer, with approximately 30% or 18,414 being stage III/IV patients. Based on genomic characterization studies of endometrial cancer, 20-25% of patients have tumors with a microsatellite instability phenotype (MSI-H)2. Microsatellite instability arises from a failure to repair replication-associated errors due to a defective DNA mismatch repair system. This failure allows persistence of mismatch mutations all over the genome, but especially in regions of repetitive DNA known as microsatellites, leading to increased mutational load that has been demonstrated to improve responses to anti-PD-1 therapies.3,4

On June 5, 2017 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that new data for TECENTRIQ and updates from across its extensive cancer immunotherapy clinical development programme will be presented during the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on 2 June – 6 June in Chicago, Illinois, United States (Press release, Hoffmann-La Roche, JUN 3, 2017, View Source [SID1234519439]). Data from phase I, II and Phase III studies presented at ASCO (Free ASCO Whitepaper) 2017 suggest that TECENTRIQ 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.

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Data from a study of TECENTRIQ plus Avastin in metastatic Renal Cell Carcinoma (mRCC) supports a scientific rationale for combining TECENTRIQ with Avastin including its potential to increase infiltration (trafficking) of T-cells into tumours and other immune-modulatory properties. New data will also be presented for TECENTRIQ as a monotherapy from the OAK trial, which represent the first treatment-beyond-progression data from a Phase III study of cancer immunotherapy in advanced lung cancer (NSCLC). Updated data will also be presented from the Phase Ib study of TECENTRIQ in combination with chemotherapy for people with advanced NSCLC. Two Phase Ib studies in melanoma combining TECENTRIQ plus Cotellic (cobimetinib) and TECENTRIQ plus Cotellic plus Zelboraf (vemurafenib) showed that the addition of Zelboraf and/or Cotellic may alter the tumour micro environment, enhancing the anti-tumour activity of TECENTRIQ.

"By applying our seminal research in immune tumour profiling within the framework of the Roche-devised cancer immunity cycle, we are accelerating and expanding the transformative benefits with TECENTRIQ to a greater number of people living with cancer," said Sandra Horning, MD, Chief Medical Officer and Head of Global Product Development. "Our cancer immunotherapy development programme takes a comprehensive approach in pursuing the goal of restoring cancer immunity to improve outcomes for patients, and at ASCO (Free ASCO Whitepaper) 2017 we are presenting data from a range of medicines and combinations that we believe have this potential."
Kidney cancer (Renal Cell Carcinoma RCC)

IMmotion150 is a global, multicentre Phase II study that was designed to evaluate the efficacy and safety of TECENTRIQ plus Avastin, TECENTRIQ alone or sunitinib alone in 305 patients with previously untreated, locally advanced or mRCC. After progression on the sunitinib or TECENTRIQ arms of the study, 77% and 75% of patients crossed over to TECENTRIQ plus Avastin treatment, respectively.

Clinical activity of TECENTRIQ plus Avastin was seen in crossover patients regardless of first line TECENTRIQ or sunitinib therapy or response to first line therapy, further supporting this combination as a potential treatment option. Specifically, TECENTRIQ plus Avastin resulted in an Overall Response Rate (ORR) of 26% in all-crossover patients (28% in crossover post-sunitinib; 24% in crossover post-TECENTRIQ patients) with a median Progression Free Survival (PFS) of 8.8 months in all-crossover patients. There were no new safety signals observed in the crossover treated patients.

A Phase III study, IMmotion151, in a similar population is expected to provide initial results in early 2018.
IMmotion150: A Phase II trial in untreated metastatic renal cell carcinoma (mRCC) patients (pts) of atezolizumab (atezo) and bevacizumab (bev) vs and following atezo or sunitinib (sun). Oral abstract 4505 Monday 5 June, 08:00 – 11:00 CDT

Lung cancer
In the Phase III OAK trial, which studied the impact of TECENTRIQ treatment beyond radiologic disease progression (PD), showed that a continuation of TECENTRIQ treatment after PD resulted in promising clinical benefit. The study design allowed patients randomised to TECENTRIQ to continue treatment beyond PD, as assessed by Response Evaluation Criteria in Solid Tumours (RECIST) v1.1, if the patient was considered to be deriving clinical benefit from treatment. TECENTRIQ could be continued until there was loss of clinical benefit according to the investigator’s clinical judgement.

Patients in the TECENTRIQ arm who continued TECENTRIQ therapy beyond PD had a prolonged clinical benefit, 12.7 months Overall Survival (OS) (95% CI 9.3–14.9) compared with 8.8 months OS (6.0 – 12.1) for those treated with other anti-cancer treatments post PD. Tumour target lesion responses and stabilisation post-PD were seen across all subgroups of programmed death-ligand 1 (PD-L1) expression. These data support the treatment strategy of continuing TECENTRIQ beyond PD until loss of clinical benefit in patients, regardless of the level of PD-L1 expression.
Impact of atezolizumab (atezo) treatment beyond disease progression (TBP) in advanced NSCLC: Results from the randomised phase III OAK study. Oral abstract TPS5090
Tuesday 6 June, 09:45 – 12:45 CDT

The updated efficacy and safety data for Arms C–E of our phase Ib GP28328 study are encouraging for TECENTRIQ in combination with various chemotherapies. The primary endpoint of the study was safety and TECENTRIQ was well tolerated when combined with various chemotherapies.
Updated efficacy and safety data table for TECENTRIQ in combination Arms C–E

The confirmed ORRs and mature OS data provide further evidence for a synergy between the anti-tumour activity of TECENTRIQ and chemotherapy.
Abstract 9092, Poster Board: #418. Lung Cancer—Non-Small Cell Metastatic
Saturday 6 June, 08:00 – 11:30 CDT

Melanoma
Updated study results from two Phase Ib studies combining TECENTRIQ plus Cotellic (cobimetinib) and, TECENTRIQ plus Cotellic plus Zelboraf (vemurafenib) showed improved ORR and PFS after a longer follow up. Both combination studies demonstrated a manageable safety profile.

Based on the results of the Phase 1b studies both combinations are now in Phase III clinical trials. The TECENTRIQ plus Cotellic plus Zelboraf combination will be investigated in people with untreated BRAFV600‑mutant unresectable metastatic melanoma while the TECENTRIQ plus Cotellic combination will be studied in people with untreated, unresectable metastatic BRAF wild-type melanoma.
Atezolizumab (A) + cobimetinib (C) + vemurafenib (V) in BRAFV600-mutant metastatic melanoma (mel): Updated safety and clinical activity. Abstract 3063
Monday 5 June, 08:00 – 11:30 CDT
Atezolizumab (A) + cobimetinib (C) in metastatic melanoma (mel): Updated safety and clinical activity.
Abstract 3057
Monday 5 June, 8:00 – 11:30CDT
Pipeline
Data from two studies will be presented that demonstrate the potential of TECENTRIQ in combination with novel cancer immunotherapies. These studies include a Phase I dose escalation study evaluating the T-cell bispecific (CEA- TCB) antibody as a single agent or in combination with TECENTRIQ in patients with metastatic colorectal cancer and a Phase Ib dose-escalation study evaluating the combined inhibition of TECENTRIQ plus IDO1 (GDC-0919) in patients with locally advanced or metastatic solid tumours and
Monotherapy data will also be presented from a Phase Ia study of TECENTRIQ in advanced/recurrent endometrial cancer (rEC), a patient population for whom the prognosis remains poor. The study is evaluating clinical activity and safety. Results show that TECENTRIQ has a favourable safety profile in rEC, with durable clinical benefit seen in some patients. Clinical benefit appeared to increase with higher PD-L1 expression, suggesting a link between PD-L1 status and response.

Further information on Roche’s contribution to the ASCO (Free ASCO Whitepaper) 2017 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 Monday, 5 June 2017 at 17:15 CDT. This event is independently organised by Roche and is open to analysts attending the ASCO (Free ASCO Whitepaper) 2017 Annual Meeting. To register for the Roche investor briefing, please use the following link: http://roche.cvent.com/d/85qzfy.

To learn more about Roche’s personalised cancer immunotherapy programme and Roche’s contribution to ASCO (Free ASCO Whitepaper) 2017, please follow Roche on Twitter via @Roche. You can keep up to date with ASCO (Free ASCO Whitepaper) 2017 Annual Meeting news and updates by using the hashtag #ASCO17.
Overview of Roche cancer immunotherapy data being presented at ASCO (Free ASCO Whitepaper) 2017

On June 3, 2017 Incyte Corporation (NASDAQ:INCY) reported updated data from the advanced non-small cell lung cancer (NSCLC) patient cohort of the ongoing Phase 1/2 ECHO-202 trial, evaluating epacadostat, Incyte’s selective IDO1 enzyme inhibitor, in combination with pembrolizumab (Keytruda), an anti-PD-1 therapy marketed by Merck & Co., Inc., Kenilworth, NJ USA (known as MSD outside the United States and Canada) (Press release, Incyte, JUN 3, 2017, View Source;p=RssLanding&cat=news&id=2278620 [SID1234519423]). Data showed an overall response rate (ORR) of 35 percent (n=14/40) among all patients with advanced squamous and non-squamous NSCLC treated with the combination of epacadostat and pembrolizumab, irrespective of PD-L1 status. Findings will be highlighted in a poster discussion at the 2017 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago on Saturday, June 3, from 3:00 pm to 4:15 p.m. CDT (Location: Hall D2) (Abstracts #9014).

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"These updated data suggest that the combination of epacadostat and pembrolizumab has promise for patients with advanced NSCLC, irrespective of PD-L1 status," said ECHO-202 study investigator Tara Gangadhar, M.D., Assistant Professor of Medicine, Perelman School of Medicine at the Hospital of the University of Pennsylvania. "The results show a clinical benefit for patients with advanced lung cancer and establish a strong basis for progressing this novel, investigational immunotherapy combination into pivotal studies for the first-line treatment of these patients."

Key Findings from the ECHO-202 NSCLC Cohort
Data at ASCO (Free ASCO Whitepaper) (as of February 27, 2017) show an ORR of 35 percent (n=14/40) among all patients with advanced NSCLC treated with the combination of epacadostat and pembrolizumab, with a complete response (CR) in two patients (5%) and partial response (PR) in 12 patients (30%). The data show a disease control rate (DCR) of 63 percent (n=25/40), with 71 percent (n=10/14) of responses ongoing at the time of the data cut-off (duration of response, range: 8.9 to 76.6+ weeks). Responses were observed in patients with high levels of PD-L1 expression [tumor proportion score (TPS) ≥50%], as well as in those patients with lower levels of PD-L1 expression (TPS of less than 50%). All responses were observed in the subgroup of patients with zero to two prior lines of therapy for advanced disease.

ECHO-202 Overall Response Rates (ORR), Disease Control Rates (DCR) and Durability of Response (DoR) in Advanced NSCLC
n/N
(%)
All pts

0-2 prior lines of therapy for advanced disease
Total Total TPS ≥50%* TPS <50%*
ORR n=14/40
(35)
n=14/36
(39)
n=3/7
(43) n=6/18
(33)
2 CR (5)
12 PR (30)
2 CR (6)
12 PR (33)
all PR 1 CR (6)
5 PR (28)
DCR n=25/40
(63) n=23/36
(64)
n=4/7
(57) n=10/18
(56)
DoR 10/14 responses ongoing
Median (range) duration of response: 26.9+ (8.9 to 76.6+) weeks
*Note: PD-L1 status was not available for 11 of the 36 patients.

Among patients treated with pembrolizumab in combination with epacadostat ≥100 mg twice daily, the ORR was 40 percent (n=14/35).

The most common treatment-related adverse events (TRAEs) for epacadostat plus pembrolizumab included fatigue (28%), arthralgia (17%), nausea (14%), decreased appetite (10%), pruritus (10%), and rash (10%). Grade ≥3 TRAEs that occurred in >1 patient were limited to lipase increased (n=3), fatigue (n=2), and rash (n=2). TRAEs led to discontinuation of treatment in 5 percent of study patients. The safety profile was consistent with previously reported Phase 1 findings, as well as the Phase 1/2 safety results in other tumor cohorts and pooled safety data from this study. In general, the safety profile of the combination was also consistent with pembrolizumab monotherapy.

About ECHO-202 (KEYNOTE-037)
The ECHO-202 study (NCT02178722) is evaluating the safety and efficacy of epacadostat, Incyte’s selective IDO1 inhibitor, in combination with pembrolizumab (Keytruda). Patients previously treated with anti-PD-1 or anti-CTLA-4 therapies were excluded from this trial. Enrollment is complete for the Phase 1 dose escalation (epacadostat 25, 50, 100 mg BID + pembrolizumab 2 mg/kg IV Q3W and epacadostat 300 mg BID + pembrolizumab 200 mg IV Q3W) and Phase 1 dose expansion (epacadostat 50, 100, and 300 mg BID + pembrolizumab 200 mg IV Q3W) portions of the trial. For more information about ECHO-202, visit View Source

About ECHO
The ECHO clinical trial program was established to investigate the efficacy and safety of epacadostat as a core component of combination therapy in oncology. Ongoing Phase 1 and Phase 2 studies evaluating epacadostat in combination with PD-1 and PD-L1 inhibitors collectively plan to enroll over 900 patients in a broad range of solid tumor types as well as hematological malignancies. ECHO-301 (NCT02752074), a Phase 3 randomized, double-blind, placebo-controlled study investigating pembrolizumab (Keytruda) in combination with epacadostat or placebo for the treatment of patients with unresectable or metastatic melanoma, is also underway. For more information about the ECHO clinical trial program, visit www.ECHOClinicalTrials.com.

About Epacadostat (INCB024360)
Indoleamine 2,3-dioxygenase 1 (IDO1) is a key immunosuppressive enzyme that modulates the anti-tumor immune response by promoting regulatory T cell generation and blocking effector T cell activation, thereby facilitating tumor growth by allowing cancer cells to avoid immune surveillance. Epacadostat is an investigational, highly potent and selective oral inhibitor of the IDO1 enzyme that regulates the tumor immune microenvironment, thereby restoring effective anti-tumor immune responses. In single-arm studies, the combination of epacadostat and immune checkpoint inhibitors has shown proof-of-concept in patients with unresectable or metastatic melanoma. In these studies, epacadostat combined with the CTLA-4 inhibitor ipilimumab or the PD-1 inhibitor KEYTRUDA improved response rates compared with studies of the immune checkpoint inhibitors alone.