On Marck 14, 2017 Merck (NYSE:MRK), known as MSD outside the United States and Canada, reported that the U.S. Food and Drug Administration (FDA) has extended the action date for the supplemental Biologics License Application (sBLA) for KEYTRUDA (pembrolizumab), the company’s anti-PD-1 therapy, for previously treated patients with advanced microsatellite instability-high (MSI-H) cancer (Press release, Merck & Co, MAR 14, 2017, View Source [SID1234518116]). The company recently submitted additional data and analyses to the FDA related to the pending application. The submission of additional data is considered a major amendment to the sBLA under the Prescription Drug User Fee Act (PDUFA), thus extending the target action date by three months. The new FDA target action date is June 9, 2017.

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

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

                  Schedule Your 30 min Free Demo!

Merck continues to work closely with the FDA to support the review of this sBLA and looks forward to further advancing the science of immuno-oncology in MSI-H cancer.

About KEYTRUDA (pembrolizumab)

KEYTRUDA is a humanized monoclonal antibody that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

KEYTRUDA is administered as an intravenous infusion over 30 minutes every three weeks for the approved indications. KEYTRUDA for injection is supplied in a 100 mg single use vial.

KEYTRUDA Indications (pembrolizumab)

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.

Lung Cancer

KEYTRUDA is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression [tumor proportion score (TPS) ≥50%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA is also indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

Head and Neck Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Selected Important Safety Information for KEYTRUDA (pembrolizumab)

KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases. Pneumonitis occurred in 94 (3.4%) of 2799 patients receiving KEYTRUDA, including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%) pneumonitis, and occurred more frequently in patients with a history of prior thoracic radiation (6.9%) compared to those without (2.9%). Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.

KEYTRUDA can cause immune-mediated colitis. Colitis occurred in 48 (1.7%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.4%), 3 (1.1%), and 4 (<0.1%) colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA (pembrolizumab) for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.

KEYTRUDA can cause immune-mediated hepatitis. Hepatitis occurred in 19 (0.7%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.4%), and 4 (<0.1%) hepatitis. Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.

KEYTRUDA can cause hypophysitis. Hypophysitis occurred in 17 (0.6%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.2%), 3 (0.3%), and 4 (<0.1%) hypophysitis. Monitor patients for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency). Administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA for Grade 2; withhold or discontinue for Grade 3 or 4 hypophysitis.

KEYTRUDA can cause thyroid disorders, including hyperthyroidism, hypothyroidism, and thyroiditis. Hyperthyroidism occurred in 96 (3.4%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.8%) and 3 (0.1%) hyperthyroidism. Hypothyroidism occurred in 237 (8.5%) of 2799 patients receiving KEYTRUDA, including Grade 2 (6.2%) and 3 (0.1%) hypothyroidism. The incidence of new or worsening hypothyroidism was higher in patients with HNSCC occurring in 28 (15%) of 192 patients with HNSCC, including Grade 3 (0.5%) hypothyroidism. Thyroiditis occurred in 16 (0.6%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.3%) thyroiditis. Monitor patients for changes in thyroid function (at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation) and for clinical signs and symptoms of thyroid disorders. Administer replacement hormones for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism.

KEYTRUDA can cause type 1 diabetes mellitus, including diabetic ketoacidosis, which have been reported in 6 (0.2%) of 2799 patients. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and administer antihyperglycemics in patients with severe hyperglycemia.

KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred in 9 (0.3%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.1%), and 4 (<0.1%) nephritis. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 nephritis.

KEYTRUDA (pembrolizumab) can cause other clinically important immune-mediated adverse reactions. For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA and administer corticosteroids. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. Resume KEYTRUDA when the adverse reaction remains at Grade 1 or less following corticosteroid taper. Permanently discontinue KEYTRUDA for any Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.

The following clinically significant immune-mediated adverse reactions occurred in less than 1% (unless otherwise indicated) of 2799 patients: arthritis (1.5%), exfoliative dermatitis, bullous pemphigoid, rash (1.4%), uveitis, myositis, Guillain-Barré syndrome, myasthenia gravis, vasculitis, pancreatitis, hemolytic anemia, and partial seizures arising in a patient with inflammatory foci in brain parenchyma.

KEYTRUDA can cause severe or life-threatening infusion-related reactions, which have been reported in 6 (0.2%) of 2799 patients. Monitor patients for signs and symptoms of infusion-related reactions, including rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever. For Grade 3 or 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. If used during pregnancy, or if the patient becomes pregnant during treatment, apprise the patient of the potential hazard to a fetus. Advise females of reproductive potential to use highly effective contraception during treatment and for 4 months after the last dose of KEYTRUDA.

In KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9% of 555 patients with advanced melanoma; adverse reactions leading to discontinuation in more than one patient were colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). Adverse reactions leading to interruption of KEYTRUDA occurred in 21% of patients; the most common (≥1%) was diarrhea (2.5%). The most common adverse reactions with KEYTRUDA vs ipilimumab were fatigue (28% vs 28%), diarrhea (26% with KEYTRUDA), rash (24% vs 23%), and nausea (21% with KEYTRUDA). Corresponding incidence rates are listed for ipilimumab only for those adverse reactions that occurred at the same or lower rate than with KEYTRUDA (pembrolizumab).

KEYTRUDA was discontinued due to adverse reactions in 8% of 682 patients with metastatic NSCLC. The most common adverse event resulting in permanent discontinuation of KEYTRUDA was pneumonitis (1.8%). Adverse reactions leading to interruption of KEYTRUDA occurred in 23% of patients; the most common (≥1%) were diarrhea (1%), fatigue (1.3%), pneumonia (1%), liver enzyme elevation (1.2%), decreased appetite (1.3%), and pneumonitis (1%). The most common adverse reactions (occurring in at least 20% of patients and at a higher incidence than with docetaxel) were decreased appetite (25% vs 23%), dyspnea (23% vs 20%), and nausea (20% vs 18%).

KEYTRUDA was discontinued due to adverse reactions in 17% of 192 patients with HNSCC. Serious adverse reactions occurred in 45% of patients. The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. The most common adverse reactions (reported in at least 20% of patients) were fatigue, decreased appetite, and dyspnea. Adverse reactions occurring in patients with HNSCC were generally similar to those occurring in patients with melanoma or NSCLC, with the exception of increased incidences of facial edema (10% all Grades; 2.1% Grades 3 or 4) and new or worsening hypothyroidism.

It is not known whether KEYTRUDA is excreted in human milk. Because many drugs are excreted in human milk, instruct women to discontinue nursing during treatment with KEYTRUDA and for 4 months after the final dose.

Safety and effectiveness of KEYTRUDA have not been established in pediatric patients.

Our Focus on Cancer

Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, helping people fight cancer is our passion and supporting accessibility to our cancer medicines is our commitment. Our focus is on pursuing research in immuno-oncology and we are accelerating every step in the journey – from lab to clinic – to potentially bring new hope to people with cancer.

As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the fastest-growing development programs in the industry. We are currently executing an expansive research program that includes more than 400 clinical trials evaluating our anti-PD-1 therapy across more than 30 tumor types. We also continue to strengthen our immuno-oncology portfolio through strategic acquisitions and are prioritizing the development of several promising immunotherapeutic candidates with the potential to improve the treatment of advanced cancers.

For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.

On March 14, 2017 Kite Pharma, Inc. (Nasdaq:KITE) reported the publication of results in the Journal of Clinical Oncology from a National Cancer Institute (NCI) study of anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in patients with relapsed/refractory non-Hodgkin lymphoma (NHL) (Press release, Kite Pharma, MAR 14, 2017, View Source [SID1234518114]). The research, led by James N. Kochenderfer, M.D., an investigator in the Experimental Transplantation and Immunology Branch of the NCI Center for Cancer Research, was performed pursuant to a CRADA between NCI and Kite.

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

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

                  Schedule Your 30 min Free Demo!

In this study, 22 patients with relapsed/refractory NHL received a single dose of anti-CD19 CAR T-cell therapy after a low-dose chemotherapy conditioning regimen consisting of cyclophosphamide and fludarabine. Objective responses (OR) were seen in 73 percent of patients, and complete remissions (CR) were observed in 55 percent of patients. Among patients with aggressive B-cell NHL (diffuse large B cell lymphoma, primary mediastinal B-cell lymphoma, or transformed follicular lymphoma), OR and CR were 68 percent and 47 percent, respectively. Duration of responses ranged from 7+ months to 24+ months, and 11 of the 12 CRs were ongoing. Reversible grade 3 or 4 neurotoxicity including confusion, dysphasia, encephalopathy, and gait disturbances was observed in 55 percent of treated patients.

"We are encouraged by the durable complete remissions and key translational insights observed in this study conducted by Dr. Steven A. Rosenberg and Dr. Kochenderfer and their team at the NCI," said Jeff Wiezorek, M.D., Senior Vice President of Clinical Development of Kite. "This finding from the NCI and our ongoing clinical trials will help to inform and advance our pipeline of engineered T-cell therapies."

The study showed the low-dose conditioning regimen led to the depletion of lymphocytes and increase in serum interleukin-15 (IL-15). Blood levels of IL-15 were shown to associate with the expansion of CAR T-cells and remission of lymphoma. A similar conditioning regimen is used in Kite’s ZUMA-1 study of axicabtagene ciloleucel, Kite’s lead product candidate and investigational anti-CD19 CAR T-cell therapy.

"The data from the National Cancer Institute, which has a history of pioneering research in anti-CD19 CAR-T therapy, suggests that it is possible to achieve durable, complete remissions in patients with advanced disease who have no treatment options," said David Chang, M.D., Ph.D., Executive Vice President of Research and Development and Chief Medical Officer of Kite. "This research provides important understanding on the association of certain factors with efficacy and adverse events so we can more quickly advance our research to realize the full potential of CAR-T therapy."

DOI: 10.1200/JCO.2016.71.3024 Journal of Clinical Oncology – published online before print March 14, 2017.

On March 14, 2017 TapImmune, Inc. (NASDAQ: TPIV), a clinical-stage immuno-oncology company specializing in the development of innovative peptide and gene-based immunotherapeutics for the treatment of cancer and metastatic disease, reported that its collaborators at the Mayo Clinic, recently received a $3.7 million grant from the U.S. Department of Defense (DoD) to conduct a Phase 2 clinical study on TapImmune’s HER2/neu-targeted T-cell vaccine that will enroll women diagnosed with an early form of breast cancer called ductal carcinoma in situ (DCIS) (Press release, TapImmune, MAR 14, 2017, View Source [SID1234518113]). If successful, TapImmune’s vaccine may replace standard surgery and chemotherapy, and potentially could become part of a routine immunization schedule for preventing breast cancer in healthy women.

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

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

                  Schedule Your 30 min Free Demo!

"This is our second T-cell vaccine candidate to be tested in a DoD-funded Phase 2 study to the Mayo Clinic, and it marks our expansion into a second breast cancer indication," said Dr. Glynn Wilson, chairman and CEO of TapImmune. "In addition to ongoing and planned Phase 2 studies of our lead TPIV 200 vaccine for treating triple-negative breast cancer, this new study of our HER2neu vaccine in DCIS has the potential to validate our novel approach to establishing lasting immunity against breast cancer and precancerous lesions. Her2neu is overexpressed in about 30% of all breast cancer patients amounting to approximately 220,00 patients per year. We look forward to the advancement of this fully funded study, as it further broadens our robust clinical pipeline, which also includes two additional Phase 2 trials for treating ovarian cancer."

The study is expected to begin in 2017 and will be led by Keith Knutson, Ph.D., Director of the Discovery and Translational Labs Cancer Research Program at Mayo Clinic’s Florida campus. It is expected to enroll 40-45 women with DCIS, who will receive the vaccine six weeks prior to standard surgical resection. The vaccine has already been shown to stimulate production of T-cells directed against breast cancer cells that overexpress the oncogene HER2 in a completed Phase 1 study.

TapImmune has licensed the HER2neu vaccine technology that will be used in this study and has the worldwide exclusive rights to commercialize the technology. TapImmune will be funded for providing the manufactured product for this trial.

Dr. Knutson added, "DCIS is a significant health problem, accounting for about 20% of U.S. cases of breast cancer. We ultimately want to eliminate ductal carcinoma in situ, which means preventing disfiguring surgeries and toxic therapies in the 60,000 women who receive this diagnosis every year in the U.S."

On March 14, 2017 AstraZeneca reported results from the Phase III SOLO-2 trial demonstrating a significant improvement in progression-free survival (PFS) in germline BRCA-mutated (gBRCA), platinum-sensitive, relapsed ovarian cancer patients treated with Lynparza (olaparib) tablets (300mg twice daily) compared with placebo in the maintenance setting (Press release, AstraZeneca, MAR 14, 2017, View Source [SID1234518106]). The trial met its primary endpoint of investigator assessed PFS (HR 0.30; 95% CI 0.22 to 0.41; P<0.0001; median 19.1 months vs 5.5 months).

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

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

                  Schedule Your 30 min Free Demo!

PFS as measured by Blinded Independent Central Review (BICR) evaluation, a pre-specified analysis supporting the primary endpoint, demonstrated a median PFS of 30.2 months vs 5.5 months for placebo, representing an improvement of 24.7 months (HR 0.25; 95% CI 0.18-0.35; P<0.0001).

Additionally, a statistically-significant benefit in time to second progression or death (PFS2) was also seen in patients treated with Lynparza (HR 0.50; 95% CI 0.34 to 0.72; P=0.0002; median not reached vs 18.4 months) compared with placebo, as well as improvements in other key secondary endpoints.

Progression-Free Survival by investigator and BICR assessment:

Analysis
Median progression-free survival, months
Hazard ratio
Investigator-assessed analysis
Lynparza
19.1

0.30 (95% CI, 0.22-0.41), P<0.0001
Placebo

5.5

Blinded Independent Central Review
Lynparza

30.2

0.25 (95% CI, 0.18-0.35), P<0.0001
Placebo

5.5

These results, presented at the Society of Gynecologic Oncology Annual Meeting on Women’s Cancer in National Harbor, USA, build upon prior data in this setting, demonstrating the benefit of Lynparza as a maintenance therapy in relapsed ovarian cancer. Eric Pujade-Lauraine, Head of the Women Cancers and Clinical Research Department at Hôpitaux Universitaires Paris Centre, site Hôtel-Dieu, AP-HP and Principal Investigator of SOLO-2, said: "Today’s results are very encouraging, as they build upon previous trials examining Lynparza in platinum-sensitive relapsed BRCA-mutated ovarian cancer. Most importantly, patients were able to maintain quality of life while experiencing an impressive delay in disease progression, demonstrating the benefits of Lynparza tablets for these women whose cancer is often difficult to treat." Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: "We are extremely pleased with the results from SOLO2, which support the potential benefit of Lynparza tablets as a maintenance therapy for patients with relapsed ovarian cancer. The tablet formulation may offer patients a reduced pill burden for Lynparza and a safety profile that is generally consistent with previous trials. We will work with regulatory authorities to make Lynparza tablets available to patients as quickly as possible." The safety profile for patients treated with Lynparza tablets during the trial was consistent to those observed with the currently-approved capsule formulation. Any adverse events (AE) Grade ≥3 were reported in 36.9% of patients treated with Lynparza and in 18.2% of patients who received placebo. The most common non-haematological AEs reported at a frequency of ≥20% were nausea (75.9% [grade ≥3, 2.6%]), fatigue/asthenia (65.6% [grade ≥3, 4.1%]), and vomiting (37.4% [≥3, 2.6%]). The most common haematological AEs reported in the Lynparza arm versus placebo were anaemia (43.6% [grade ≥3, 19.5%]), neutropenia (19.5% [grade ≥3, 5.1%]), and thrombocytopenia (13.8% [grade ≥3, 1.0%]). The 300mg twice-daily tablet dose reduces the pill burden for patients from sixteen capsules to four tablets per day.

NOTES TO EDITORS

About SOLO-2
SOLO-2 was a Phase III, randomised, double-blind, multicentre trial designed to determine the efficacy of Lynparza tablets as a maintenance monotherapy compared with placebo, in patients with platinum-sensitive relapsed or recurrent gBRCA-mutated (BRCAm) ovarian cancer. The trial, conducted in collaboration with the European Network for Gynaecological Oncological Trial Groups (ENGOT) and Groupe d’Investigateurs National pour l’Etude des Cancers de l’Ovaire et du sein (GINECO), randomised 295 patients with documented germline BRCA1 or BRCA2 mutations who had received at least 2 prior lines of platinum-based chemotherapy and were in complete or partial response. Eligible patients were randomised to receive 300mg Lynparza tablets twice daily or placebo tablets twice daily.

About Lynparza
Lynparza (olaparib) is an innovative, first-in-class oral poly ADP-ribose polymerase (PARP) inhibitor that may exploit tumour DNA damage response (DDR) pathway deficiencies to preferentially kill cancer cells. It is approved by regulatory authorities in the EU and US for the treatment of women with BRCAm ovarian cancer. Lynparza is the foundation of AstraZeneca’s industry-leading portfolio of compounds targeting DNA damage response (DDR) mechanisms in cancer cells. In a previous study Lynparza capsules were shown to result in a significant improvement in PFS compared to placebo in platinum-sensitive, relapsed ovarian cancer (PSR OC) patients (HR 0.35; 95% CI 0.25-0.49; p <0.0001) as well as in the subgroup of patients whose tumours harbour BRCA mutations (HR 0.18; 95% CI 0.10-0.31; p <0.0001).

About ENGOT
ENGOT (European Network for Gynaecological Oncological Trial groups) is a research network of the European Society of Gynaecological Oncology (ESGO) and was founded in 2007. Currently, ENGOT consists of 19 cooperative groups from 15 European countries. ENGOT’s ultimate goal is to bring the best treatment to gynaecological cancer patients through the best science, and enabling every patient in every European country to access a clinical trial. ENGOT coordinates and promotes multinational clinical trials within Europe on patients with gynaecological cancer. This coordination is particularly relevant for academic clinical trials, translational research, research on rare diseases, and for clinical trials sponsored by the industry.

About GINECO
GINECO (Groupe d’Investigateurs National pour l’Etude des Cancers de l’Ovaire et du sein) is the French Cooperative Group in Oncology labelled by INCA (Institut National du Cancer or French NCI) for developing and conducting gynaecological and advanced breast cancer clinical trials at the national and international level. The network is nationwide with 700 specialized investigators belonging to more than 150 public or private oncology units. The GINECO group was founded in 1993 and is member of international consortia such as ENGOT and GCIG (Gynecologic Cancer InterGroup). GINECO was the ENGOT leading group for SOLO-2 trial.