AACR Annual Meeting Highlights Week in Cancer News

Top news of the week in oncology and cancer drug development.

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FDA Grants Full Approval to Frontline Palbociclib in Breast Cancer

The FDA has granted a full approval to palbociclib (Ibrance) for use in combination with letrozole as a frontline treatment for postmenopausal women with ER-positive, HER2-negative metastatic breast cancer. The full approval of the CDK 4/6 inhibitor is based on the phase III PALOMA-2 trial, in which adding palbociclib to letrozole reduced the risk of disease progression by 42% compared with letrozole alone.

The investigator-assessed median progression-free survival (PFS) with the palbociclib combination was 24.8 months versus 14.5 months with letrozole alone (HR, 0.58; 95% CI, 0.46-0.72; P <.0001). The median PFS by blinded independent central review was 30.5 months versus 19.3 months, respectively (HR, 0.65; 95% CI, 0.51-0.84; P = .0005). The objective response rate was 42% with the combination versus 35% in the control group. The PFS benefit with palbociclib was sustained across subgroups.

See more: http://www.onclive.com/web-exclusives/fda-grants-full-approval-to-frontline-palbociclib-in-breast-cancer

Osimertinib Receives Full FDA Approval for T790M+ NSCLC

The FDA has granted a regular approval to osimertinib (Tagrisso) as a treatment for patients with metastatic EGFR T790M mutation-positive non—small cell lung cancer following prior treatment with an EGFR TKI, based on progression-free survival (PFS) findings from the phase III AURA3 trial. In the randomized trial, osimertinib demonstrated a median PFS of 10.1 months compared with 4.4 months for standard platinum-based chemotherapy (HR, 0.30; 95% CI, 0.23-0.41; P <.001).

The median PFS for patients with central nervous system metastases was 8.5 months with osimertinib versus 4.2 months with chemotherapy (HR, 0.32; 95% CI, 0.21-0.49). Osimertinib was originally granted an accelerated approval in November 2015, based on an overall response rates of 59% across 2 single-arm studies.

See more: http://www.onclive.com/web-exclusives/fda-grants-full-approval-to-osimertinib-for-t790m-nsclc

FDA Grants Priority Review to CTL019 for ALL

The FDA has granted a priority review designation to tisagenlecleucel-T (CTL019) as a treatment for pediatric and young adult patients with relapsed and refractory B-cell acute lymphoblastic leukemia. The biologics license application for tisagenlecleucel-T is based primarily on findings from the phase II ELIANA study, in which the complete remission (CR) or CR with incomplete blood count recovery rate was 82% with tisagenlecleucel-T, the 6-month overall survival rate was 89%, and the disease-free survival rate was 60%.

The CR rate was 68% with tisagenlecleucel-T, and 14% of patients had a CRi. All patients with a CR/CRi also tested negative for minimal residual disease (95% CI, 69-91; P <.0001).

See more: http://www.onclive.com/web-exclusives/fda-grants-priority-review-to-ctl019-for-all

Priority Review Granted to sBLA for Full Approval of Blinatumomab in ALL

The FDA has granted a priority review to a supplemental biologics license application (sBLA) supporting the conversion of the accelerated approval of blinatumomab (Blincyto) to a full approval as a treatment for patients with Philadelphia chromosome-negative relapsed/refractory B-precursor acute lymphoblastic leukemia.

The sBLA for the anti-CD19 agent is based on the phase III TOWER trial, in which treatment with blinatumomab led to a median overall survival of 7.7 months versus 4 months with standard chemotherapy. The application also provides data supporting the use of blinatumomab in patients with Philadelphia chromosome-positive relapsed/refractory B-cell precursor ALL.

See more: http://www.onclive.com/web-exclusives/fda-grants-priority-review-to-sbla-for-full-approval-of-blinatumomab-in-all

FDA Panel Supports Subcutaneous Rituximab for Blood Cancers

The FDA’s Oncologic Drugs Advisory Committee unanimously (11-0) recommended approval of subcutaneous rituximab for the treatment of patients with certain blood cancers. The novel co-formulation includes the identical monoclonal antibody as intravenous rituximab (Rituxan), along with the molecule hyaluronidase, which facilitates the delivery of medicine beneath the skin.

The proposed indications for the treatment include previously untreated follicular lymphoma, previously untreated diffuse large B-cell lymphoma, relapsed or refractory low grade or follicular lymphoma, and previously untreated and relapsed or refractory chronic lymphocytic leukemia. A final approval decision is expected from the FDA by June 26, 2017.

See more: http://www.onclive.com/web-exclusives/fda-panel-supports-subcutaneous-rituximab-for-blood-cancers

Application for Axicabtagene Ciloleucel in NHL Submitted to FDA

A biologics license application (BLA) has been submitted for the CAR T-cell therapy axicabtagene ciloleucel (KTE-C19) as a potential treatment for transplant ineligible patients with relapsed or refractory aggressive non-Hodgkin lymphoma (NHL). The BLA was based on findings from the phase II ZUMA-1 study, in which axicabtagene ciloleucel demonstrated an objective response rate of 82% and a complete response rate of 54% for patients with NHL.

Responses were seen across subgroups in the study, including those with diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, and transformed follicular lymphoma. The application was completed following a rolling submission of data, which was permitted as part of a breakthrough therapy designation received in December 2015.

See more: http://www.onclive.com/web-exclusives/fda-submission-completed-for-axicabtagene-ciloleucel-in-nhl

FDA Accepts Ibrutinib Application for GVHD

The FDA has accepted a supplemental new drug application (sNDA) for ibrutinib (Imbruvica) as a treatment for patients with chronic graft-versus-host-disease (cGVHD) after failure of 1 or more lines of systemic therapy. The sNDA is based on data from the single-arm phase Ib/II PCYC-1129 trial, which were first presented during the 2016 ASH Annual Meeting. In the study, ibrutinib induced an overall response rate of 67% and showed clinically meaningful and durable responses in patients who failed at least 1 prior treatment for cGVHD.

Twenty-one percent of responders had a complete response and 45% had a partial response. Additionally, most responders were able to reduce steroid doses to an acceptable minimal level. Under its standard review process, the FDA will issue its final decision on the ibrutinib sBLA within 12 months from the time of submission.

See more: http://www.onclive.com/web-exclusives/fda-accepts-ibrutinib-application-for-gvhd

Alectinib Improves PFS in Phase III ALK+ NSCLC Trial

Alectinib (Alecensa) significantly improved progression-free survival (PFS) compared with chemotherapy in patients with ALK-positive non—small cell lung cancer (NSCLC) who had progressed following treatment with platinum-based chemotherapy and crizotinib (Xalkori), according to findings from the phase III ALUR trial. The randomized, open-label trial included 119 patients across 15 countries.

Roche, the the developer of the second-generation ALK inhibitor alectinib, reported that the full study data will be published in a peer-reviewed publication later this year. The FDA approved alectinib in December 2015 as a treatment for patients with metastatic ALK-positive NSCLC following progression on crizotinib, based on findings from 2 phase II clinical trials.

See more: http://www.onclive.com/web-exclusives/alectinib-improves-pfs-in-phase-iii-alk-nsclc-trial

Dabrafenib/Trametinib Combo Wins EU Approval for BRAF+ NSCLC

The European Union approved the combination of dabrafenib (Tafinlar) and trametinib (Mekinist) for patients with BRAF V600-positive advanced or metastatic non—small cell lung cancer. The approval is based on a phase II study in which 36 treatment-naïve patients and 57 previously-treated patients were assigned to 150 mg twice daily of dabrafenib and 2 mg once daily of trametinib.

The overall response rate (ORR) was 61.1% (95% CI, 43.5-76.9) in the treatment-naïve group, and 68% of patients did not show progression. The ORR was 66.7% (95% CI, 52.9-78.6) in the previously treated population.

See more: http://www.onclive.com/web-exclusives/dabrafenibtrametinib-combo-wins-eu-approval-for-braf-nsclc

2017 AACR Annual Meeting Highlights

Nivolumab/Ipilimumab Combo Shows Modest OS Benefit in Advanced Melanoma in Updated

The PD-1 and CTLA-4 inhibitor combination of nivolumab (Opdivo) and ipilimumab (Yervoy) was associated with a 12% reduction in the risk of death versus nivolumab monotherapy in patients with treatment-naïve advanced melanoma.

See more: http://www.onclive.com/conference-coverage/aacr-2017/nivolumabipilimumab-combo-shows-modest-os-benefit-in-advanced-melanoma-in-updated-phase-iii-findings

Five-Year Survival Rate an Impressive 16% With Nivolumab in Advanced NSCLC

Long-term survival in patients with metastatic non—small cell lung cancer who received the immune checkpoint inhibitor nivolumab (Opdivo) has proven to be much higher than expected, with 16% of these patients surviving after 5 years, equivalent to about 4 times what would be expected with chemotherapy.

See more: http://www.onclive.com/conference-coverage/aacr-2017/fiveyear-survival-rate-an-impressive-16-with-nivolumab-in-advanced-nsclc

Atezolizumab Yields Long-Term OS in mTNBC Subset

According to results presented at the 2017 AACR Annual Meeting, 10% of patients showed impressive long-term survival in a phase I study of single-agent anti&shy;—PD-L1 atezolizumab (Tecentriq) in patients with metastatic triple-negative breast cancer.

See more: http://www.onclive.com/conference-coverage/aacr-2017/aacr-report-atezolizumab-yields-longterm-os-in-mtnbc-subset

CAR T-Cell Response Rate Tops 80% in NHL Trial

Results of a phase II trial showed that more than 80% of patients with refractory non-Hodgkin lymphoma achieved objective responses to treatment with the chimeric antigen receptor T-cell therapy axicabtagene ciloleucel.

See more: http://www.onclive.com/conference-coverage/aacr-2017/car-tcell-response-rate-tops-80-in-nhl-trial

Neratinib Shows Promise in HER2-Mutated Cancers

The irreversible pan-HER tyrosine kinase inhibitor neratinib showed single-agent activity across cohorts of patients with HER2-mutant advanced cancers. http://www.onclive.com/conference-coverage/aacr-2017/neratinib-shows-promise-in-some-her2mutated-cancers

IDO Inhibitor Increases Pembrolizumab Response in Melanoma

Adding the IDO inhibitor indoximod to pembrolizumab (Keytruda) led to an overall response rate of 52% in patients with advanced melanoma, according to findings from a phase II trial reported at the 2017 AACR Annual Meeting.

See more: http://www.onclive.com/conference-coverage/aacr-2017/ido-inhibitor-increases-pembrolizumab-response-in-melanoma

For full AACR meeting coverage, go to http://www.onclive.com/conference-coverage/aacr-2017