on September 20, 2021 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that new data from the Phase III IMpower010 study at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2021 Presidential Symposium, reinforcing the significant disease-free survival (DFS) benefit offered by Tecentriq (atezolizumab) for people with Stage II-IIIA non-small cell lung cancer (NSCLC) whose tumours express PD-L1≥1%. Data from the IMpower010 trial were published simultaneously in The Lancet (Press release, Hoffmann-La Roche, SEP 20, 2021, View Source [SID1234587967]). In IMpower010, treatment with Tecentriq, following surgery and chemotherapy, reduced the risk of disease recurrence or death (DFS) by 34% (hazard ratio [HR]=0.66, 95% CI: 0.50–0.88) in people with Stage II-IIIA NSCLC whose tumours express PD-L1≥1%, compared with best supportive care (BSC). Safety data for Tecentriq were consistent with its known safety profile and no new safety signals were identified.

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"Today, more than half of all people with early-stage NSCLC experience recurrence following surgery," said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. "IMpower010 shows how, for the first time, a cancer immunotherapy may help many of these patients live longer without their disease returning. The data presented at ESMO (Free ESMO Whitepaper) and WCLC further contribute to our understanding of Tecentriq in this treatment setting."

At the 2021 ESMO (Free ESMO Whitepaper) Virtual Congress, new real-world data show that almost three-quarters of patients with early-stage NSCLC in the US did not receive adjuvant treatment, despite guideline recommendations.1 Data presented from IMpower010 show that adjuvant Tecentriq offers a DFS benefit in the Stage II-IIIA patient population, irrespective of the stage of disease and across the main prior therapies.2,3 Specifically, time to relapse appeared to be improved with Tecentriq, compared with BSC, among people with Stage II-IIIA NSCLC whose tumours express PD-L1 TC ≥1%, for both locoregional and distant sites. There was no clear difference in patterns of relapse. An extended analysis of PD-L1 subgroups in the Stage II-IIIA population shows there is a higher magnitude of benefit from adjuvant Tecentriq in people with PD-L1 expression ≥50%, compared with those with 1-49% PD-L1 expression.2 The exploratory nature of the analysis in patients with 1-49% PD-L1 expression prevents any firm conclusions, and these data will be further analysed and shared at a future medical congress.

Additional IMpower010 data, recently presented at the International Association for the Study of Lung Cancer (IASLC) 2021 World Conference on Lung Cancer (WCLC) Presidential Symposium, showed that treatment with Tecentriq improved DFS in the PD-L1≥1% Stage II-IIIA NSCLC population, compared with BSC, regardless of most surgery types and adjuvant chemotherapy regimens.3

Based on the IMpower010 data, the US Food and Drug Administration (FDA) recently granted Priority Review to Tecentriq as an adjuvant treatment for certain people with early NSCLC and is reviewing the application under the Real-Time Oncology Review pilot programme, which aims to explore a more efficient review process to ensure safe and effective treatments are available to patients as early as possible. The FDA is expected to make a decision on approval by 1 December 2021.

Tecentriq has previously shown clinically meaningful benefit in various types of lung cancer, with five currently approved indications in markets around the world. It was the first approved cancer immunotherapy for front-line treatment of adults with extensive-stage small cell lung cancer (SCLC) in combination with carboplatin and etoposide (chemotherapy). Tecentriq also has four approved indications in advanced NSCLC as either a single agent or in combination with targeted therapies and/or chemotherapies. Tecentriq is available in three dosing options, providing the flexibility to choose administration every two, three or four weeks.

Roche has an extensive development programme for Tecentriq, including multiple ongoing and planned Phase III studies across different settings in lung, genitourinary, skin, breast, gastrointestinal, gynaecological, and head and neck cancers. This includes studies evaluating Tecentriq both alone and in combination with other medicines, as well as studies in metastatic, adjuvant and neoadjuvant settings across various tumour types.

About the IMpower010 study
IMpower010 is a Phase III, global, multicentre, open-label, randomised study evaluating the efficacy and safety of Tecentriq compared with BSC, in participants with Stage IB-IIIA NSCLC (UICC 7th edition), following surgical resection and up to 4 cycles of adjuvant cisplatin-based chemotherapy. The study randomised 1,005 people with a ratio of 1:1 to receive either Tecentriq (up to 16 cycles) or BSC. The primary endpoint is investigator-determined DFS in the PD-L1-positive Stage II-IIIA, all randomised Stage II-IIIA and ITT Stage IB-IIIA populations. Key secondary endpoints include OS in the overall study population, ITT Stage IB-IIIA NSCLC.

About NSCLC
Lung cancer is one of the leading causes of cancer death globally.4 Each year 1.8 million people die as a result of the disease; this translates into more than 4,900 deaths worldwide every day.4 Lung cancer can be broadly divided into two major types: NSCLC and SCLC. NSCLC is the most prevalent type, accounting for around 85% of all cases.5 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.5

About Tecentriq
Tecentriq is a monoclonal antibody designed to bind with a protein called Programmed Death Ligand-1 (PD-L1), which is 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 is a cancer immunotherapy that has the potential to be used as a foundational combination partner with other immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers. The development of Tecentriq and its clinical programme is based on our greater understanding of how the immune system interacts with tumours and how harnessing a person’s immune system combats cancer more effectively.

Tecentriq is approved in the US, EU and countries around the world, either alone or in combination with targeted therapies and/or chemotherapies in various forms of NSCLC, SCLC, certain types of metastatic urothelial cancer, in PD-L1-positive metastatic triple-negative breast cancer and for hepatocellular carcinoma. In the US, Tecentriq is also approved in combination with Cotellic (cobimetinib) and Zelboraf (vemurafenib) for the treatment of people with BRAF V600 mutation-positive advanced melanoma.

About Roche in cancer immunotherapy
Roche’s rigorous pursuit of groundbreaking science has contributed to major therapeutic and diagnostic advances in oncology over the last 50 years, and today, realising the full potential of cancer immunotherapy is a major area of focus. With over 20 molecules in development, Roche is investigating the potential benefits of immunotherapy alone, and in combination with chemotherapy, targeted therapies or other immunotherapies with the goal of providing each person with a treatment tailored to harness their own unique immune system to attack their cancer. Our scientific expertise, coupled with innovative pipeline and extensive partnerships, gives us the confidence to continue pursuing the vision of finding a cure for cancer by ensuring the right treatment for the right patient at the right time.

In addition to Roche’s approved PD-L1 checkpoint inhibitor, Tecentriq (atezolizumab), Roche’s broad cancer immunotherapy pipeline includes other checkpoint inhibitors, such as tiragolumab, a novel cancer immunotherapy designed to bind to TIGIT, individualised neoantigen therapies and T-cell bispecific antibodies.

To learn more about Roche’s scientific-led approach to cancer immunotherapy, please follow this link:

On September 20, 2021 Exelixis, Inc. (Nasdaq: EXEL) reported final results from the phase 3 COSMIC-311 pivotal trial of CABOMETYX (cabozantinib) in patients with previously treated radioactive iodine-refractory differentiated thyroid cancer (DTC) (Press release, Exelixis, SEP 20, 2021, View Source [SID1234587962]). Following a previous announcement that the trial met one of the two primary endpoints of significant improvement versus placebo in progression-free survival (PFS) assessed by blinded independent radiology committee (BIRC; p<0.0001), the results of the final analysis are being presented during the Mini Oral Session – NETs and Endocrine Tumours at 5:30 p.m. CEST on Monday, September 20 at the 2021 European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress (LBA67). At a median follow-up of 10.1 months, the significant improvement in PFS with CABOMETYX was maintained, with consistent benefit in subgroups based on prior treatment.

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"Given the urgent need for new treatments for differentiated thyroid cancer, I’m encouraged to see that cabozantinib benefited patients in COSMIC-311 both at a longer follow-up and across prior therapy subgroups," said Jaume Capdevila, M.D., Ph.D., Medical Oncologist at Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology (VHIO), Barcelona, and a COSMIC-311 study investigator. "These strong findings, which formed the basis for the recent U.S. FDA approval, further support cabozantinib as an important new treatment option for patients with radioactive iodine-refractory differentiated thyroid cancer who previously had no standard of care following disease progression on anti-VEGFR therapy."

At a median follow-up of 10.1 months, CABOMETYX reduced the risk of disease progression or death versus placebo (hazard ratio [HR]: 0.22; 96% confidence interval [CI]: 0.15–0.32) in the intent-to-treat (ITT) population. Median PFS as assessed by BIRC was 11.0 months for patients treated with CABOMETYX (n=170) compared with 1.9 months for patients treated with placebo (n=88). Subgroup analyses demonstrated that CABOMETYX improved PFS versus placebo irrespective of prior exposure to lenvatinib and/or sorafenib:

Prior sorafenib/no lenvatinib: median PFS was 16.6 months for patients treated with CABOMETYX (n=63) compared with 3.2 months for placebo (n=33) (HR: 0.13; 95% CI: 0.06–0.26).
Prior lenvatinib/no sorafenib: median PFS was 5.8 months for patients treated with CABOMETYX (n=68) compared with 1.9 months for placebo (n=34) (HR: 0.28; 95% CI: 0.16–0.48).
Prior sorafenib and lenvatinib: median PFS was 7.6 months for patients treated with CABOMETYX (n=39) compared with 1.9 months for placebo (n=21) (HR: 0.27; 95% CI: 0.13–0.54).
An updated analysis for the primary endpoint of objective response rate (ORR) as assessed by BIRC in the ITT population favored CABOMETYX at 11%, including one complete response, versus 0% for placebo. Median overall survival, an additional endpoint, was 19.4 months for patients treated with CABOMETYX and not estimable for patients treated with placebo (HR: 0.76; 95% CI: 0.45–1.31).

The safety profile was consistent with that previously observed for CABOMETYX, and adverse events (AEs) were managed with dose modifications. The discontinuation rate due to treatment-emergent AEs was 8.8% for CABOMETYX versus 0% for placebo. Rates of grade 3/4 treatment-emergent AEs were 62% for CABOMETYX versus 28% for placebo, with no treatment-related deaths. Dose reductions due to AEs were required in 67% of patients treated with CABOMETYX versus 5% for placebo.

"Following the recent U.S. FDA approval, we are pleased to share these detailed results at this year’s ESMO (Free ESMO Whitepaper) which show CABOMETYX continued to benefit these patients with advanced differentiated thyroid cancer in the trial at a longer follow-up," said Michael M. Morrissey, Ph.D., President and Chief Executive Officer, Exelixis. "This patient population faces a poor prognosis and previously had very limited treatment options. We are thrilled that eligible patients in the U.S. now have CABOMETYX as an approved treatment option and will continue to work with our partners on their efforts to bring CABOMETYX to even more patients worldwide."

Results from COSMIC-311 served as the basis for the September 17, 2021 U.S. Food and Drug Administration (FDA) approval of CABOMETYX for the treatment of adult and pediatric patients 12 years of age and older with locally advanced or metastatic DTC that has progressed following prior vascular endothelial growth factor receptor (VEGFR)-targeted therapy and who are radioactive iodine-refractory or ineligible. The application was approved well ahead of the Prescription Drug User Fee Act (PDUFA) target action date of December 4, 2021.

About COSMIC-311
COSMIC-311 was a multicenter, randomized, double-blind, placebo-controlled phase 3 pivotal trial that enrolled 258 patients at 164 sites globally. Patients were randomized in a 2:1 ratio to receive either CABOMETYX 60 mg or placebo once daily. The primary endpoints were PFS and ORR. Exelixis is sponsoring COSMIC-311, and Ipsen is co-funding the trial. More information about this trial is available at ClinicalTrials.gov.

About DTC
Approximately 44,000 new cases of thyroid cancer will be diagnosed in the U.S. in 2021.1 Nearly three out of four of these cases will be in women, and the disease is more commonly diagnosed at a younger age compared to most other adult cancers.2 While cancerous thyroid tumors include differentiated, medullary and anaplastic forms, differentiated thyroid tumors make up about 90% of cases.2 These include papillary, follicular and Hürthle cell cancer.2 DTC is typically treated with surgery followed by ablation of the remaining thyroid tissue with radioiodine, but approximately 5% to 15% of cases are resistant to radioiodine treatment. 2,3 For these patients, life expectancy is only three to five years from the time metastatic lesions are detected.4,5,6

About CABOMETYX (cabozantinib)
In the U.S., CABOMETYX tablets are approved for the treatment of patients with advanced renal cell carcinoma (RCC); for the treatment of patients with hepatocellular carcinoma who have been previously treated with sorafenib; for patients with advanced RCC as a first-line treatment in combination with nivolumab; and for adult and pediatric patients 12 years of age and older with locally advanced or metastatic DTC that has progressed following prior VEGFR-targeted therapy and who are radioactive iodine-refractory or ineligible. CABOMETYX tablets have also received regulatory approvals in the European Union and additional countries and regions worldwide. In 2016, Exelixis granted Ipsen exclusive rights for the commercialization and further clinical development of cabozantinib outside of the U.S. and Japan. In 2017, Exelixis granted exclusive rights to Takeda Pharmaceutical Company Limited for the commercialization and further clinical development of cabozantinib for all future indications in Japan. Exelixis holds the exclusive rights to develop and commercialize cabozantinib in the U.S.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hemorrhage: Severe and fatal hemorrhages occurred with CABOMETYX. The incidence of Grade 3 to 5 hemorrhagic events was 5% in CABOMETYX patients in RCC, HCC, and DTC studies. Discontinue CABOMETYX for Grade 3 or 4 hemorrhage and prior to surgery as recommended. Do not administer CABOMETYX to patients who have a recent history of hemorrhage, including hemoptysis, hematemesis, or melena.

Perforations and Fistulas: Fistulas, including fatal cases, occurred in 1% of CABOMETYX patients. Gastrointestinal (GI) perforations, including fatal cases, occurred in 1% of CABOMETYX patients. Monitor patients for signs and symptoms of fistulas and perforations, including abscess and sepsis. Discontinue CABOMETYX in patients who experience a Grade 4 fistula or a GI perforation.

Thrombotic Events: CABOMETYX increased the risk of thrombotic events. Venous thromboembolism occurred in 7% (including 4% pulmonary embolism) and arterial thromboembolism in 2% of CABOMETYX patients. Fatal thrombotic events occurred in CABOMETYX patients. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or serious arterial or venous thromboembolic events that require medical intervention.

Hypertension and Hypertensive Crisis: CABOMETYX can cause hypertension, including hypertensive crisis. Hypertension was reported in 37% (16% Grade 3 and <1% Grade 4) of CABOMETYX patients. Do not initiate CABOMETYX in patients with uncontrolled hypertension. Monitor blood pressure regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled with medical management; when controlled, resume at a reduced dose. Permanently discontinue CABOMETYX for severe hypertension that cannot be controlled with anti-hypertensive therapy or for hypertensive crisis.

Diarrhea: Diarrhea occurred in 62% of CABOMETYX patients. Grade 3 diarrhea occurred in 10% of CABOMETYX patients. Monitor and manage patients using antidiarrheals as indicated. Withhold CABOMETYX until improvement to ≤ Grade 1, resume at a reduced dose.

Palmar-Plantar Erythrodysesthesia (PPE): PPE occurred in 45% of CABOMETYX patients. Grade 3 PPE occurred in 13% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 PPE or Grade 3 PPE.

Hepatotoxicity: CABOMETYX in combination with nivolumab can cause hepatic toxicity with higher frequencies of Grades 3 and 4 ALT and AST elevations compared to CABOMETYX alone.

Monitor liver enzymes before initiation of and periodically throughout treatment. Consider more frequent monitoring of liver enzymes than when the drugs are administered as single agents. For elevated liver enzymes, interrupt CABOMETYX and nivolumab and consider administering corticosteroids.

With the combination of CABOMETYX and nivolumab, Grades 3 and 4 increased ALT or AST were seen in 11% of patients. ALT or AST >3 times ULN (Grade ≥2) was reported in 83 patients, of whom 23 (28%) received systemic corticosteroids; ALT or AST resolved to Grades 0-1 in 74 (89%). Among the 44 patients with Grade ≥2 increased ALT or AST who were rechallenged with either CABOMETYX (n=9) or nivolumab (n=11) as a single agent or with both (n=24), recurrence of Grade ≥2 increased ALT or AST was observed in 2 patients receiving CABOMETYX, 2 patients receiving nivolumab, and 7 patients receiving both CABOMETYX and nivolumab. Withhold and resume at a reduced dose based on severity.

Adrenal Insufficiency: CABOMETYX in combination with nivolumab can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold CABOMETYX and/or nivolumab and resume CABOMETYX at a reduced dose depending on severity.

Adrenal insufficiency occurred in 4.7% (15/320) of patients with RCC who received CABOMETYX with nivolumab, including Grade 3 (2.2%), and Grade 2 (1.9%) adverse reactions. Adrenal insufficiency led to permanent discontinuation of CABOMETYX and nivolumab in 0.9% and withholding of CABOMETYX and nivolumab in 2.8% of patients with RCC.

Approximately 80% (12/15) of patients with adrenal insufficiency received hormone replacement therapy, including systemic corticosteroids. Adrenal insufficiency resolved in 27% (n=4) of the 15 patients. Of the 9 patients in whom CABOMETYX with nivolumab was withheld for adrenal insufficiency, 6 reinstated treatment after symptom improvement; of these, all (n=6) received hormone replacement therapy and 2 had recurrence of adrenal insufficiency.

Proteinuria: Proteinuria was observed in 8% of CABOMETYX patients. Monitor urine protein regularly during CABOMETYX treatment. For Grade 2 or 3 proteinuria, withhold CABOMETYX until improvement to ≤ Grade 1 proteinuria, resume CABOMETYX at a reduced dose. Discontinue CABOMETYX in patients who develop nephrotic syndrome.

Osteonecrosis of the Jaw (ONJ): ONJ occurred in <1% of CABOMETYX patients. ONJ can manifest as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration or erosion, persistent jaw pain, or slow healing of the mouth or jaw after dental surgery. Perform an oral examination prior to CABOMETYX initiation and periodically during treatment. Advise patients regarding good oral hygiene practices. Withhold CABOMETYX for at least 3 weeks prior to scheduled dental surgery or invasive dental procedures, if possible. Withhold CABOMETYX for development of ONJ until complete resolution, resume at a reduced dose.

Impaired Wound Healing: Wound complications occurred with CABOMETYX. Withhold CABOMETYX for at least 3 weeks prior to elective surgery. Do not administer CABOMETYX for at least 2 weeks after major surgery and until adequate wound healing. The safety of resumption of CABOMETYX after resolution of wound healing complications has not been established.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): RPLS, a syndrome of subcortical vasogenic edema diagnosed by characteristic findings on MRI, can occur with CABOMETYX. Evaluate for RPLS in patients presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.

Thyroid Dysfunction: Thyroid dysfunction, primarily hypothyroidism, has been observed with CABOMETYX. Based on the safety population, thyroid dysfunction occurred in 19% of patients treated with CABOMETYX, including Grade 3 in 0.4% of patients.

Patients should be assessed for signs of thyroid dysfunction prior to the initiation of CABOMETYX and monitored for signs and symptoms of thyroid dysfunction during CABOMETYX treatment. Thyroid function testing and management of dysfunction should be performed as clinically indicated.

Hypocalcemia: CABOMETYX can cause hypocalcemia. Based on the safety population, hypocalcemia occurred in 13% of patients treated with CABOMETYX, including Grade 3 in 2% and Grade 4 in 1% of patients. Laboratory abnormality data were not collected in CABOSUN.

In COSMIC-311, hypocalcemia occurred in 36% of patients treated with CABOMETYX, including Grade 3 in 6% and Grade 4 in 3% of patients.

Monitor blood calcium levels and replace calcium as necessary during treatment. Withhold and resume at reduced dose upon recovery or permanently discontinue CABOMETYX depending on severity.

Embryo-Fetal Toxicity: CABOMETYX can cause fetal harm. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Verify the pregnancy status of females of reproductive potential prior to initiating CABOMETYX and advise them to use effective contraception during treatment and for 4 months after the last dose.

ADVERSE REACTIONS

The most common (≥20%) adverse reactions are:

CABOMETYX as a single agent: diarrhea, fatigue, PPE, decreased appetite, hypertension, nausea, vomiting, weight decreased, constipation.

CABOMETYX in combination with nivolumab: diarrhea, fatigue, hepatotoxicity, PPE, stomatitis, rash, hypertension, hypothyroidism, musculoskeletal pain, decreased appetite, nausea, dysgeusia, abdominal pain, cough, and upper respiratory tract infection.

DRUG INTERACTIONS

Strong CYP3A4 Inhibitors: If coadministration with strong CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage. Avoid grapefruit or grapefruit juice.

Strong CYP3A4 Inducers: If coadministration with strong CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage. Avoid St. John’s wort.

USE IN SPECIFIC POPULATIONS

Lactation: Advise women not to breastfeed during CABOMETYX treatment and for 4 months after the final dose.

Hepatic Impairment: In patients with moderate hepatic impairment, reduce the CABOMETYX dosage. Avoid CABOMETYX in patients with severe hepatic impairment.

Please see accompanying full Prescribing Information
View Source

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.FDA.gov/medwatch or call 1-800-FDA-1088.

On September 20, 2021 EORTC reported that Late-breaking results from two Phase 2 EORTC trials of immunotherapy were presented at the 2021 European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) congress on Friday 17 September (Press release, EORTC, SEP 20, 2021, View Source [SID1234587961]). Immunotherapy drugs are relatively new additions to cancer treatment, and work by stimulating the immune system so that it can find and attack cancer cells. Over the past few decades, this has become an important part of treating some cancers and more new ways of utilising the immune system to this end are being discovered all the time.

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Dr Susana Banerjee, a consultant medical oncologist from the Royal Marsden NHS Foundation Trust and Institute of Cancer Research, London, UK, presented results from the EORTC-15081 trial of different combinations of the immunotherapy drug atezolizumab with bevacizumab, targeted therapy against VEGF, and bevacizumab with acetylsalicylic acid or placebo in recurrent ovarian, fallopian tube or primary peritoneal adenocarcinomas that were resistant to platinum-based chemotherapy. Results to date of the use of immunotherapy alone in women with relapsed ovarian cancer have, overall, been rather disappointing, says Dr Banerjee. "Based on lab work, the EORTC Gynaecological Cancers group set out to investigate whether targeting the cells surrounding the tumour in addition to immune cells might improve outcomes for women with platinum-resistant ovarian cancer."

The researchers recruited and randomised 122 patients from 12 sites in five countries to receive different combinations of the treatments being studied. They found that, while tumour response did not differ, the time to first subsequent therapy (TFST) was longer in those patients who had received bevacizumab plus atezolizumab therapy compared to bevacizumab alone, and that the addition of acetylsalicylic acid (aspirin) did not appear to improve the efficacy of treatment.

"Our results suggest that the chemotherapy-free combination of bevacizumab and atezolizumab could delay the time to the next cancer treatment. Additionally, there are few patients who have continued on this treatment for much longer than others without their cancer worsening, and it will be important for us to understand why this is," says Dr Banerjee.

The researchers now intend to follow up their results by analysing patient samples to understand which patients may benefit most and to identify potential predictive markers.

In the second presentation, Dr Nicolas Girard, from the Institut Curie, Paris, France, described results from the EORTC-ETOP NIVOTHYM2 trial of nivolumab and ipilimumab in patients with thymic tumours who were no longer responding to chemotherapy. Thymic tumours are rare and difficult to treat. They form in the cells covering the thymus, a small organ of the upper chest, near to the heart, and which forms part of the lymphatic system. "Immunotherapy is a new option for the patients for whom there was no longer any available standard therapy with this tumour," says Dr Girard.

The trial design includes two groups – one receiving nivolumab alone and the other nivolumab plus ipilimumab. In the nivolumab only group, 55 patients were enrolled in 15 centers across five countries. After a median follow-up of 13.3 months, results from this group showed that nivolumab had been discontinued in 45 cases, primarily due to progression of the disease.

"However, the safety profile of nivolumab was manageable, and disease control was achieved in 63% of these patients. We are now working to try to identify predictors for the efficacy of immunotherapy in the patients enrolled in the trial. We now know that nivolumab alone does not live up to our first, optimistic expectations, even though we have been able to show the efficacy of immunotherapy. Our aim now is to increase the duration of efficacy with the addition of ipilimumab, and we hope to be able to report first results by quarter 3 of 2023," says Dr Girard.

1. LBA32 – Principal results of the EORTC-1508 trial: A phase II randomised, multicentre study of bevacizumab vs atezolizumab and bevacizumab with acetylsalicylic acid or placebo in recurrent platinum-resistant ovarian, fallopian tube or primary peritoneal adenocarcinoma

2. LBA66 – Efficacy and safety of nivolumab for patients with pre-treated type B3 thymoma and thymic carcinoma: Results from the EORTC-ETOP NIVOTHYM phase II trial

On September 20, 2021 Clovis Oncology, Inc. (NASDAQ:CLVS) reported that it has paid off in full at maturity the remaining $64.4 million in principal amount outstanding of its 2.50% convertible senior notes due 2021 (Press release, Clovis Oncology, SEP 20, 2021, View Source [SID1234587959]). In addition, the Company provided an update on the progress of its renewed "at-the-market" (ATM) equity offering program announced in mid-August, pursuant to which it has sold during the third quarter of 2021 to date an aggregate of approximately 9.4 million shares of its common stock for gross proceeds of approximately $43.0 million and resulting in net proceeds to Clovis Oncology of approximately $41.7 million after commissions and offering related expenses. This is in addition to the previously announced approximately $72.5 million in net proceeds raised by Clovis Oncology pursuant to its ATM equity offering program during the second quarter of 2021.

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"These activities improve our balance sheet and complement our ongoing focus on cost control as we look forward to the potentially transformative events of 2022," said Patrick J. Mahaffy, President and CEO of Clovis Oncology. "In 2022, we anticipate three Phase 3 data read-outs for Rubraca, which offer the potential to significantly expand the number of ovarian and prostate cancer patients eligible for Rubraca treatment in the US and Europe. In addition, we are enthusiastic about our ongoing Phase 1 LuMIERE study of FAP-2286 in advanced solid tumors, and expect the presentation of initial Phase 1 data at a medical meeting in 2022. Each of these supports our three key strategies: expand the Rubraca label to drive revenue growth, emerge as a leader in targeted radionuclide therapy, and achieve long-term financial stability."

Three anticipated data readouts from Rubraca studies are anticipated in 2022: ATHENA monotherapy in first-line maintenance treatment ovarian cancer in Q1 2022, TRITON3 monotherapy in second-line metastatic castration-resistant prostate cancer in Q2 2022, and ATHENA combination with Opdivo infirst-line maintenance treatment ovarian cancer in 2H 2022. These data read-outs provide the potential to reach larger patient populations in earlier lines of therapy for ovarian and prostate cancers. The timing of each of these read-outs is contingent upon the occurrence of the protocol-specified progression-free survival events.

FAP-2286 is Clovis Oncology’s peptide-targeted radionuclide therapy (PTRT) and imaging agent targeting fibroblast activation protein (FAP) and is the lead candidate in the Company’s TRT development program. The Phase 1 portion of the LuMIERE study is evaluating the safety of the FAP-targeting investigational therapeutic agent and will identify the recommended Phase 2 dose and schedule of lutetium-177 labeled FAP-2286. FAP-2286 labeled with gallium-68 will be used as an investigational imaging agent to identify patients with FAP-positive tumors appropriate for treatment in LuMIERE. The first presentation of Phase 1 data from LuMIERE is expected at a medical meeting in 2022. Once the Phase 2 dose is determined, Phase 2 expansion cohorts are planned in multiple tumor types and expected to initiate in 2022.

Sales of its common stock under the ATM equity offering program were made by Clovis Oncology pursuant to a prospectus supplement filed with the U.S. Securities and Exchange Commission. This press release is for informational purposes only and is not an offer to sell or the solicitation of an offer to buy any securities of Clovis Oncology.

On September 20, 2021 The Case Comprehensive Cancer Center, Northeast Ohio’s coordinated effort to combat cancer, reported that it has earned an additional $12 million from the National Cancer Institute (NCI) as a two-year merit-based extension (Press release, Case Western Reserve University, SEP 20, 2021, View Source [SID1234587958]). The center is the first of two NCI-designated cancer centers to be awarded this prestigious distinction, only available to top-tier centers in the country.

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The center’s current Cancer Center Support Grant was last renewed in 2017 when it received an "exceptional" rating—the highest possible—along with $27.9 million to continue lifesaving work from 2018-2023. The Cancer Center’s recent application to extend this funding was approved based on its sustained exceptional progress, stability and longevity.

"This is a fantastic achievement for the Case Comprehensive Cancer Center," said Alan Diehl, deputy director and chief operating officer for the Case Comprehensive Cancer Center and the Leonard and Jean Skeggs Professor and chair of the Department of Biochemistry at the Case Western Reserve School of Medicine. "The merit extension reflects the leadership by Director Stan Gerson and an exceptional team, all of whom focus on providing the best cancer interventions available to our community. It is an honor to be part of such a dynamic partnership."

Photo of Stan Gerson
Stan Gerson
Stan Gerson, interim dean and the Asa and Patricia Shiverick-Jane Shiverick (Tripp) Professor of Hematological Oncology at the Case Western Reserve School of Medicine, has led the center since 2004. He has been continuously recognized for his leadership and for developing such initiatives as implementing a strategic planning effort and enhanced transdisciplinary collaborations, dedicating efforts to address health disparities and community health, and recruiting talented senior leaders and researchers.

"We are humbled to be one of the first centers to receive this new extension and hope a number of other exceptional centers will soon follow," Gerson said. "Our consortium is quite robust and committed to the highest quality of cancer research and impact. This extension will allow us to seamlessly continue driving research focused on the diagnosis, treatment and prevention of cancer, directly impacting the patients and communities we serve."

Among the center’s recent achievements over the past year:

A retreat of program leaders with its Community Advisory Board coordinated by its Office of Community Outreach and Engagement.
Implementation of a strong support program for diversity and equity.
Development of a new "disease ribbons" concept that helps link the breadth of disease-focused research across programs and into translational and clinical applications.
The center is one of just 51 NCI-designated comprehensive cancer centers nationally and one of a small handful to earn the exceptional rating. More than 400 physicians and scientists across the three partner institutions are brought together through six scientific research programs: Cancer Genomics & Epigenomics, Molecular Oncology, Immune Oncology, Developmental Therapeutics, Cancer Imaging, and Population & Cancer Prevention.

The center is known for being a research leader in basic, clinical and population sciences and for providing exemplary service to Northeast Ohio. In addition, the center has built a national reputation for research in colorectal cancers, leukemia and myelodysplastic syndrome (MDS), brain, lung, kidney and prostate cancers.

Combined, Cleveland Clinic and University Hospitals treat nearly 19,000 new cancer patients each year. Because these hospitals are part of an NCI-designated comprehensive cancer center, these patients have more opportunities to participate in a broad range of cutting-edge clinical trials; they also benefit from the concentration of expertise among the three organizations.

"We are grateful for this merit extension, which is a testament to the outstanding research and patient care delivered by Cleveland Clinic Taussig Cancer Institute and Case Comprehensive Cancer Center," said Jame Abraham, deputy director for Cleveland Clinic, Case Comprehensive Cancer Center, acting chair of the Cleveland Clinic Taussig Cancer Institute and a professor at Case Western Reserve School of Medicine. "This support by the National Cancer Institute will allow us to continue focusing on exploring the intricacies of cancer and discovering new treatment options for our patients."

"University Hospitals celebrates the well-deserved merit extension granted by the National Cancer Institute to the Case Comprehensive Cancer Center," said Theodoros N. Teknos, deputy director for University Hospitals for the Case Comprehensive Cancer Center, president and scientific director of University Hospitals Seidman Cancer Center, and a professor of otolaryngology at Case Western Reserve’s School of Medicine. "This recognition serves as validation that Cleveland’s major research institutions are at the forefront of discoveries in cancer prevention, early detection and cure."

The center is also lauded for its training, education and career-development programs for cancer trainees, from high school through junior faculty. In addition, it is home to the NCI-supported Paul Calabresi Clinical Oncology Scholar Training to support clinical investigators across the institutions, one of the longest-running awards of this type in the country. Since its founding in 1987 by Case Western Reserve and University Hospitals, the center has held an NCI designation and attained "comprehensive" status in 1998. Cleveland Clinic formally joined the consortium in 2003.