On June 2, 2018 Odonate Therapeutics, Inc. (NASDAQ: ODT), a pharmaceutical company dedicated to the development of best-in-class therapeutics that improve and extend the lives of patients with cancer, reported that results from a multicenter Phase 2 study of tesetaxel, administered orally as a single agent to patients with HER2 negative, hormone receptor (HR) positive, metastatic breast cancer (MBC), were presented at the 2018 ASCO (Free ASCO Whitepaper) Annual Meeting in Chicago, Illinois(Poster Board #123; Abstract #1042) (Press release, Odonate Therapeutics, JUN 2, 2018, View Source [SID1234527106]).

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In this Phase 2 study (Study TOB203), 38 patients with HER2 negative, HR positive, MBC received tesetaxel orally as a single agent once every 3 weeks (Q3W) at a starting dose of 27 mg/m2. Eighty-seven percent (87%) had visceral disease, 74% previously received at least one endocrine therapy, 68% previously received neoadjuvant or adjuvant chemotherapy and 53% previously received a taxane-containing regimen. Objective response rate (ORR) based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 with confirmation no less than 4 weeks after initial response was the primary endpoint.

In all 38 patients, the confirmed response rate was 45%. The confirmed response rate was consistent across subgroups. Forty-four percent (44%) of patients who did not previously receive a taxane-containing regimen achieved a confirmed response, compared to 45% of patients who previously received a taxane-containing regimen. Median duration of response was 10.9 months, and median progression-free survival was 5.4 months.

Neutropenia was the most common Grade ≥3 adverse event and occurred in 25% of the 24 patients who were not dose-escalated beyond the 27 mg/m2 starting dose (the dose selected for CONTESSA, our ongoing Phase 3 study (Poster Board #184a; Abstract #TPS1106); in these patients, febrile neutropenia occurred in 1 patient (4%) and Grade ≥3 neuropathy occurred in 1 patient (4%). There were no hypersensitivity reactions or drug-related deaths, and the rate of Grade 2 alopecia (hair loss) was 18%.

"Despite recent advances in the treatment of advanced breast cancer, there remains a significant need for new therapies that allow patients to maintain a better quality of life," said Joyce O’Shaughnessy, M.D., Celebrating Women Chair in Breast Cancer Research, Baylor University Medical Center, Texas Oncology and Chair, Breast Cancer Research, US Oncology.

"Tesetaxel’s significant single-agent activity, once-every-three-week oral dosing and low rates of neuropathy and hair loss could make this investigational agent a unique treatment option for patients, if approved," said Andrew Seidman, M.D., Attending Physician and Associate Chair, Academic Administration, Department of Medicine, Memorial Sloan Kettering Cancer Center (MSKCC) and Professor of Medicine, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medical College. "We look forward to further characterizing tesetaxel’s therapeutic profile in CONTESSA, an ongoing Phase 3 study."

About Tesetaxel

Tesetaxel is an investigational, orally administered chemotherapy agent that belongs to a class of drugs known as taxanes, which are widely used in the treatment of cancer. Tesetaxel has several potential therapeutic advantages over currently available taxanes, including: oral administration with a low pill burden and a patient-friendly dosing regimen; no history of hypersensitivity (allergic) reactions; and significant activity against chemotherapy-resistant tumors. More than 500 patients have been treated with tesetaxel in clinical studies. In patients with metastatic breast cancer, tesetaxel was shown to have significant, single-agent antitumor activity in two, multicenter, Phase 2 studies.

About CONTESSA

CONTESSA is a multinational, multicenter, randomized, Phase 3 study of tesetaxel, an investigational, orally administered taxane, in patients with locally advanced or metastatic breast cancer (LA/MBC). CONTESSA is comparing tesetaxel dosed orally at 27 mg/m2 on the first day of a 21-day cycle plus a reduced dose of capecitabine (1,650 mg/m2/day dosed orally on days 1-14 of a 21-day cycle) to the approved dose of capecitabine alone (2,500 mg/m2/day dosed orally on days 1-14 of a 21-day cycle) in approximately 600 patients randomized 1:1 with HER2 negative, hormone receptor (HR) positive LA/MBC previously treated with a taxane in the neoadjuvant or adjuvant setting. Capecitabine is an oral chemotherapy agent that is considered a standard-of-care treatment in LA/MBC. Where indicated, patients must have received endocrine therapy with or without a cyclin-dependent kinase (CDK) 4/6 inhibitor. The primary endpoint is progression-free survival (PFS) assessed by an Independent Radiologic Review Committee (IRC). CONTESSA’s secondary efficacy endpoints are overall survival, objective response rate (ORR) assessed by IRC and disease control rate assessed by IRC. To learn more, please visit www.contessastudy.com.

On June 2, 2018 Loxo Oncology, Inc. (Nasdaq:LOXO), a biopharmaceutical company developing highly selective medicines for patients with genomically defined cancers, reported interim clinical data from the LOXO-292 global Phase 1 LIBRETTO-001 (LOXO-292 Investigated to Block RET-altered Tumors) dose escalation trial (Press release, Loxo Oncology, JUN 2, 2018, View Source [SID1234527090]). LOXO-292 is an investigational, highly potent and selective RET inhibitor. These data are being presented today at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago (abstract 102).

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"The LOXO-292 Phase 1 data are striking," said Alexander Drilon, M.D., clinical director in the Early Drug Development Service at Memorial Sloan Kettering Cancer Center and presenting author. "The activity we reported is impressive and I am thrilled to see this promising efficacy with limited adverse events, especially in this heavily pre-treated patient population of RET fusion cancers, including those with brain metastases, and RET mutated MTC."

"We are very excited to share the initial LOXO-292 clinical experience with the oncology community at ASCO (Free ASCO Whitepaper)," said Josh Bilenker, M.D., chief executive officer of Loxo Oncology. "We have long believed that patients with RET fusion cancers and RET mutated MTC needed a purpose-built medicine tailored to their tumors. We hope that LOXO-292 continues to deliver on that premise. Thank you to the patients, investigators and clinical trial teams who made possible today’s presentation."

Trial Background

The LIBRETTO-001 Phase 1 trial contains a dose escalation phase and a dose expansion phase. The dose escalation phase follows a "3+3" design. LOXO-292 is dosed orally in 28-day cycles. As dose cohorts are cleared, additional patients can enroll in these cleared cohorts. Intra-patient dose escalation is also permitted as dose cohorts are cleared. The primary endpoint of the trial is the determination of the maximum tolerated dose (MTD) or recommended dose for further study. Secondary endpoints include safety, overall response rate (by RECIST 1.1) and duration of response. The dose expansion phase is designed to further characterize the overall response rate, durability of response, and safety of LOXO-292 in predefined groups of patients with activating RET alterations.

Key Data Presented at ASCO (Free ASCO Whitepaper)

The data presented at ASCO (Free ASCO Whitepaper) were based on an April 2, 2018 data cut-off date. Eighty-two total patients had been enrolled to eight dose escalation cohorts: 20 mg QD (n=6), 20 mg BID (n=10), 40 mg BID (n=16), 60 mg BID (n=10), 80 mg BID (n=18), 120 mg BID (n=4), 160 mg BID (n=12) and 240 mg BID (n=6). RET alterations were identified by local laboratories either in tumor or plasma and included the following primary diagnoses:

38 patients with RET fusion-positive non-small cell lung cancer (NSCLC) (21 with prior MKI treatment, 17 without)
9 patients with RET fusion-positive thyroid cancer (8 with prior MKI treatment, 1 without)
2 patients with RET fusion-positive pancreatic cancer (1 with prior MKI treatment, 1 without)
29 patients with RET-mutated medullary thyroid cancer (MTC) (23 with prior MKI treatment, 6 without)
4 patients with no known activating RET alterations
In addition to many patients with prior MKI treatment, 46% of patients had received prior chemotherapy and 24% had received prior immunotherapy (47% of those with NSCLC).

Pharmacokinetic analyses during the dose escalation demonstrated dose-dependent increases in LOXO-292 exposure with increasing dose. Starting at the 40 mg BID dose and the 80 mg BID dose, respectively, LOXO-292 delivered sustained >IC90 RET fusion and >IC90 RET M918T-mutant target coverage, based on cell-based potencies.

The data presented at ASCO (Free ASCO Whitepaper), summarized below, are based on response assessments performed by each respective clinical trial site (local, investigator-assessed radiology).

1. Patients eligible for response evaluation include thyroid cancer (n=7), pancreatic cancer (n=2).
2. Excludes patients recently enrolled that remain on treatment, but have not had a first post-baseline response assessment.
3. Response status per RECIST 1.1. Overall response rate = CR+uCR+PR+uPR. Overall response rate, Confirmed overall response rate: all RET fusion-positive (30/39, 25/34), RET fusion-positive NSCLC (23/30, 20/27), RET fusion-positive other (7/9, 5/7), RET-mutant MTC (10/22, 6/18).
4. Excludes patients with unconfirmed CR/PR pending confirmation at time of data cut-off.
5. Unconfirmed responses in patients that remain on treatment awaiting a confirmatory response assessment.
6. Patients that discontinued treatment prior to a first post-baseline response assessment.

Anti-tumor activity was observed regardless of RET fusion partner (including KIF5B), RET mutation (including M918T and V804M gatekeeper mutations), and prior MKI treatment. Twelve patients with RET fusion cancers had central nervous system (CNS) metastases at enrollment and all remained on study without progression. Three of these patients had RECIST target lesions in the CNS, and all three exhibited intracranial partial responses. In patients with RET-mutant MTC, LOXO-292 treatment resulted in significant reductions in the serum tumor markers calcitonin and carcinoembryonic antigen (CEA).

As of the data cutoff, LOXO-292 demonstrated early evidence of durable activity, with 90% of RET fusion-positive cancer patients and 93% of RET-mutant MTC patients remaining on therapy. All responding patients across all tumor types remained on therapy. The longest responding patient on therapy was the first RET fusion-positive NSCLC patient enrolled, who had been on therapy for more than ten months as of the data cut-off date.

Most treatment-emergent adverse events were Grade 1 in severity. The treatment-emergent adverse events observed in ≥10% of patients, regardless of relationship to LOXO-292, were fatigue (12% Grade 1, 7% Grade 2, 0% ≥Grade 3), diarrhea (10% Grade 1, 6% Grade 2, 0% ≥Grade 3), constipation (13% Grade 1, 1% Grade 2, 0% ≥Grade 3), dry mouth (12% Grade 1, 0% ≥Grade 2), nausea (9% Grade 1, 4% Grade 2, 0% ≥Grade 3), and dyspnea (7% Grade 1, 2% Grade 2, 1% ≥Grade 3). Only two adverse events ≥Grade 3 were attributed to LOXO-292 (Grade 3 tumor lysis syndrome, Grade 3 increased ALT). An MTD had not been reached. At the 240 mg BID dose level, one dose limiting toxicity (DLT) was reported (aforementioned Grade 3 tumor lysis syndrome).

LOXO-292 also demonstrated robust reduction and clearance of RET alterations as detected in patients’ plasma cell free DNA (cfDNA). These data will be presented in a separate poster presentation on June 3, 2018.

LIBRETTO-001 Trial Update

The expansion cohorts of the LIBRETTO-001 trial are now open and enrolling at the 160 mg BID dose. This dose was selected for initial expansion based on its promising activity and tolerability profile. Additional dose exploration above 160 mg BID is ongoing and patients enrolled to the expansion cohorts may dose escalate should a higher dose be advanced.

About the ASCO (Free ASCO Whitepaper) Presentations

LOXO-292 data are being presented in two presentations at ASCO (Free ASCO Whitepaper):

"A phase 1 study of LOXO-292, a potent and highly selective RET inhibitor, in patients with RET-altered cancers." This abstract is being presented in an oral presentation by Dr. Alexander Drilon, Memorial Sloan Kettering Cancer Center, during a Clinical Science Symposium session entitled, "Tumor Genomics: Finding the Target, Hitting the Target" from 8:00 – 9:30AM CT on Saturday, June 2, 2018 (Abstract 102).
"Detection and clearance of RET variants in plasma cell free DNA (cfDNA) from patients (pts) treated with LOXO-292." This abstract is being presented as a poster by Dr. Geoff Oxnard, Dana Farber Cancer Institute, during the Lung Cancer—Non-Small Cell Metastatic poster session from 8:00 – 11:30AM CT on Sunday, June 3, 2018 (Abstract 9048).
The presentations will be available online at View Source at the time of their scheduled presentation at ASCO (Free ASCO Whitepaper).

Conference Call and Webcast Information
Loxo Oncology management will host a conference call and live webcast with slides and Q&A today at 4:00 p.m. CT to discuss the LOXO-292 data. To participate in the conference call, please dial (877) 930-8065 (domestic) or (253) 336-8041 (international) and refer to conference ID 3597058. A live webcast of the presentation will be available at View Source A replay of the webcast will be available shortly after the conclusion of the call and archived on the company’s website for 30 days following the call.

On June 2, 2018 AstraZeneca and MedImmune, its global biologics research and development arm, reported that results from the Phase III (‘1053’) clinical trial (Abstract #7004) that evaluated moxetumomab pasudotox in 80 patients with relapsed or refractory hairy cell leukemia (HCL) who had received at least two prior lines of therapy.1 (Press release, AstraZeneca, JUN 2, 2018, View Source [SID1234527107])

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Moxetumomab pasudotox, an investigational anti-CD22 recombinant immunotoxin, showed a 75% objective response (OR) rate, a 41% complete response (CR) rate, and a 30% durable CR rate (primary endpoint). The majority of patients with a complete response had a durable response (73%; 24/33) and achieved a negative minimal residual disease (MRD) status (82%; 27/33). Findings from this pivotal trial were presented for the first time during an oral session at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago.

Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: "Moxetumomab pasudotox is an investigational, first-in-class immunotoxin which we believe has the potential to advance outcomes for patients with relapsed or refractory hairy cell leukemia, a condition with a high unmet need. It is also the first agent to be submitted for regulatory review from our Antibody Drug Conjugates platform, and as such demonstrates our commitment to developing novel treatments for blood cancer."

Robert J. Kreitman, MD, Senior Investigator, Head of Clinical Immunotherapy Section, Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, said: "Hairy cell leukemia is a rare, chronic blood cancer with no established standard of care for patients with relapsed or refractory disease following purine nucleoside analog therapy. With very few treatments available, there remains significant unmet medical need for people with relapsed or refractory disease. The response rates observed in this trial, and elimination of the residual leukemia cells that cause relapse in some patients, highlight the potential impact this potential new medicine could have on patients and the management of this disease."

Summary of key results from the Phase III ‘1053’ single arm, multicenter clinical trial in 80 patients with relapsed or refractory HCL (16.7 months median follow-up), as determined by a blinded independent central review:

The primary endpoint of the trial was durable CR, which is defined as CR with HR for >180 days. The median time to HR was 1 month. MRD refers to the small amounts of cancer cells that may remain after treatment.2 A high rate of negative MRD after therapy may further improve outcomes.3 The median duration of OR and median progression-free survival were not reached.

The most frequent treatment-related adverse events (AEs) were nausea (28%), peripheral edema (26%), headache (21%), and pyrexia (20%); 8% had infections and 3% had neutropenia deemed treatment-related. Three patient deaths occurred, none of which were determined to be treatment-related. Treatment-related AEs leading to discontinuation were hemolytic uremic syndrome (HUS; 4 [5%]), capillary leak syndrome (CLS; 2 [3%]), and increased blood creatinine (2 [3%]). Seven patients (9%) had CLS and seven (9%) had HUS; this includes four (5%) patients who had both CLS and HUS. CLS and HUS were manageable and reversible.

In April 2018, AstraZeneca announced that the US Food and Drug Administration (FDA) accepted the Biologics License Application (BLA) for moxetumomab pasudotox for the treatment of adult patients with HCL who have received at least two prior lines of therapy. The BLA is based on results from the Phase III ‘1053’ clinical trial. The FDA has granted Priority Review status with a Prescription Drug User Fee Act action date set for the third quarter of 2018.

NOTES TO EDITORS

About Moxetumomab Pasudotox

Moxetumomab pasudotox (formerly CAT-8015 or HA22) is an investigational anti-CD22 recombinant immunotoxin and a potential new medicine with the opportunity to be a first-in-class treatment in the US for patients with relapsed or refractory hairy cell leukemia (HCL) who have received at least two prior lines of therapy. Immunotoxins are a class of anticancer agents that combine the selectivity of antibodies to target drug delivery and the potency of toxins to kill target cancer cells.4 Moxetumomab pasudotox is composed of a binding portion of an anti-CD22 antibody fused to a toxin. CD22 is a B-lymphocyte restricted transmembrane protein with a higher receptor density in HCL cells relative to normal B cells, making it an attractive therapeutic target for the treatment of this cancer.5 After binding to CD22, the molecule is internalized, processed and releases its modified protein toxin that inhibits protein synthesis, leading to apoptotic cell death. Moxetumomab pasudotox has been granted Orphan Drug Designation by the FDA for the treatment of HCL.

About Hairy Cell Leukemia

HCL is a rare, incurable slow-growing leukemia in which the bone marrow overproduces abnormal B cells or lymphocytes.6 HCL can result in serious and life-threatening conditions, including infections, bleeding and anemia.7 Approximately 1,000 people are diagnosed with HCL in the US each year.8,9,10 While many patients initially respond to treatment, up to 40% will relapse.11 With no established standard of care and very few treatments available, there remains significant unmet medical need for people with relapsed or refractory HCL.12,13

About the ‘1053’ Phase III Trial

The ‘1053’ trial is a single-arm, multicenter Phase III clinical trial assessing the efficacy, safety, immunogenicity and pharmacokinetics of moxetumomab pasudotox monotherapy in patients with relapsed or refractory HCL who have received at least two prior therapies. The trial is being conducted in 80 patients across 34 sites in 14 countries.14 The primary endpoint was durable complete response (CR), defined as CR with hematologic remission (blood count normalization) for >180 days. Secondary outcome measures included overall response rate, relapse free survival, progression-free survival, time to response, safety, pharmacokinetic and immunogenic potential.14

On June 2, 2018 X4 Pharmaceuticals, a clinical stage biotechnology company developing novel CXCR4 antagonists to improve immune cell trafficking to treat cancer and rare diseases, reported positive clinical results from the Phase 2 expansion of an ongoing Phase 1/2 study of X4P-001-IO in combination with Inlyta (axitinib) in patients with clear cell renal cell carcinoma (ccRCC).

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The results were the first from the Phase 2 portion of the study and demonstrated that the combination was well tolerated with a manageable safety profile and had encouraging response in heavily pretreated patients. In patients with ccRCC, the combination treatment of X4P-001-IO, a CXCR4 antagonist, and Inlyta, Pfizer’s VEGFR kinase inhibitor, showed an objective response rate (ORR) of 23%, including 1 patient with a confirmed complete response (CR). Nearly 75% of patients received at least two prior lines of therapy prior to entering the study. The data were presented at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on June 2nd in Chicago, IL.

"X4P represents a novel targeted mechanism of action with demonstrated tolerability and promising efficacy in combination with axitinib in patients with pretreated renal cancer. The results from this study demonstrate that X4P-001-IO has the potential to enhance clinical responses to axitinib and other tyrosine kinase inhibitors that target tumor angiogenesis," said Ulka Vaishampayan, MD, Chair, Karmanos Cancer Center, Professor of Oncology at Wayne State University, and lead investigator of the study.

Results from the 65 patients with advanced ccRCC enrolled in the ongoing study (as of the data cutoff date of March 23, 2018) were presented at ASCO (Free ASCO Whitepaper) and highlights of the poster presentation include:

The combination of 400 mg X4P-001-IO administered once daily and 5 mg axitinib twice daily was well tolerated with a manageable safety profile. The most frequent treatment-related adverse events (AEs) were diarrhea, decreased appetite, fatigue, hypertension, nausea, headache and cough. No grade 4 or 5 AEs were observed.
In the 47 evaluable patients, the overall response rate (ORR) was 23% with one patient achieving a confirmed complete response (CR). Response data from the remaining 18 patients is pending.
Thirteen patients remain on study for 24 weeks or more; the median duration on treatment was 16 weeks (range 2 – 96 weeks).
"These interim results represent an important step in the continued development of X4P-001-IO. In this larger patient population, where many patients are still very early in treatment with the combination, we find promising signs of clinical efficacy. The tumor microenvironment modulating effect of X4P-001-IO is expected to increase and deepen responses over time, and we look forward to the maturation of the data in the coming months," said Sudha Parasuraman, MD, Chief Medical Officer of X4. "Our combined clinical experience continues to demonstrate the important role that CXCR4 antagonism may play in improving outcomes in combination with important cancer therapeutic modalities."

The Phase 2 portion of the study continues to follow patients on study to evaluate the clinical efficacy of X4P-001-IO as measured by objective response rate (ORR), duration of response (DOR), and progression free survival (PFS). (View Source)

About X4P-001-IO in Cancer

X4P-001-IO is an investigational selective, oral, small molecule antagonist of C-X-C receptor type 4 (CXCR4). CXCR4 is a chemokine receptor present in abundance on certain immune cells and cancer cells and it plays a critical role in immune cell trafficking, infiltration and activation in the tumor microenvironment. CXCR4 signaling is disrupted in a broad range of cancers, facilitating tumor growth by allowing cancer cells to evade immune detection and creating a pro-tumor microenvironment. X4P-001-IO has the ability to help restore immunity within the tumor microenvironment and has the potential to enhance the anti-tumor activity of approved and emerging oncology agents, such as checkpoint inhibitors and targeted therapies. X4P-001-IO is being investigated in several clinical studies in solid tumors.

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.

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"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.