Key Developments in Cancer Immunotherapy Research at AACR 2017

Published: April 5-6, 2017

The Society for Immunotherapy of Cancer (SITC) is pleased to present highlights of the latest advances in immunotherapy emerging from the American Association for Cancer Research (AACR) Annual Meeting 2017, held in Washington, D.C. on April 1-5, 2017.

Avelumab demonstrates sustained durable responses in patients with Merkel cell carcinoma

On the heels of the recent FDA approval of avelumab (anti-PD-L1) for the treatment of patients with metastatic Merkel cell carcinoma, SITC Immediate Past President Howard L. Kaufman, MD, FACS, Rutgers Cancer Institute of New Jersey, presented a 1-year efficacy update on the phase II JAVELIN Merkel 200 trial. Two additional patients have achieved a complete response (CR) since the primary 6-month analysis, one new CR and one previous partial response (PR) that improved to a CR. With a median follow up of 16.4 months, the objective response rate was 33%, comprised of 10 CR and 19 PR. At this point, 74% of patients have a duration of response (DOR) of one year or more; median DOR has not yet been reached. The rate of overall survival (OS) at one year was 52% and the one year progression-free survival rate was estimated to be 30%.

Survival benefit seen in patients with advanced melanoma treated with combination of nivolumab and ipilimumab

The first survival results from CheckMate 067, a phase III trial of nivolumab (anti-PD-1; “nivo”) in combination with ipilimumab (anti-CTLA-4; “ipi”) for treatment-naïve patients with advanced melanoma, were presented by James Larkin, MD, FRCP, Royal Marsden Hospital. Patients were randomized into one of three treatment groups: 1] 1 mg/kg nivo + 3 mg/kg ipi every three weeks for 4 doses, followed by 3 mg/kg nivo every other week (n=314); 2] 3 mg/kg nivo q2w + placebo (n=316); 3] 3 mg/kg ipi every three weeks for 4 doses + placebo (n=315). Descriptive analyses were presented as the study was not powered to compare between all arms. Median OS was 20 months for patients in the ipi arm, but median OS has not yet been reached in the combination or nivo arms. 2-year OS rates favored the combination (64%), while OS rates for the nivo and ipi groups were 59% and 45%, respectively. Combination therapy was associated with a 12% reduction in the risk of death compared to nivo monotherapy [hazard ratio (HR) =0.88; 95% CI, 0.69-1.12].

Trial of chimeric antigen receptor (CAR T cell therapy meets primary endpoint in patients with non-Hodgkin lymphoma (NHL)

The primary endpoint of the multi-center ZUMA-1 trial of the anti-CD19 CAR T cell, axicabtagene ciloleucel (KTE-C19) was met at the 6 month interim analysis, with an 82% objective response rate (n=92; p<0.0001) in patients with refractory, aggressive B cell NHL. In data presented by Frederick L. Locke, MD, H. Lee Moffitt Cancer Center & Research Institute, 111 patients with diffuse large B cell lymphoma, primary mediastinal B cell lymphoma, or transformed follicular lymphoma were enrolled across 22 institutions and 101 of those patients (91%) were successfully infused with a single treatment of KTE-C19 (2x106 CAR T cells/kg). Although ongoing, data at the median follow up time of 8.7 months indicate that 44% of patients remain in response, 39% have had a CR, and the median overall survival (OS) has not yet been reached. Previous reports of this study have demonstrated a manageable safety profile.

Atezolizumab induces long-term survival in responding patients with triple-negative breast cancer

Long-term survival data from an expansion cohort of a phase I trial investigating single agent atezolizumab (anti-PD-L1) for the treatment of metastatic triple-negative breast cancer (mTNBC) was presented by Peter Schmid, MD, PhD, Barts Cancer Institute. Of the evaluable patients with mTNBC, 10% (11/112) achieved either a PR or a CR and the OS rate for responding patients was 100% at 2 years. By contrast, 1- and 2-year OS for non-responders was 33% and 11%, respectively. Biomarker analyses revealed a survival benefit for patients with PD-L1 expression on ≥5% of tumor-infiltrating immune cells (1-year OS: 45%; 95% CI, 32-58) compared to patients with <5% PD-L1 expression (1-year OS: 37%; 95% CI, 21-53). Evaluation of atezolizumab as first-line treatment for TNBC is ongoing in the randomized phase III Impassion130 trial, in which atezolizumab is combined with chemotherapy.

Nivolumab induces durable overall survival in non-small cell lung cancer (NSCLC)

In the longest survival follow up of patients with NSCLC treated with an immune checkpoint inhibitor to date, Julie Brahmer, MD, Johns Hopkins, presented five-year survival data from the CA209-003 trial of nivolumab (anti-PD-1). In all, 129 heavily pretreated patients with advanced NSCLC were enrolled, of whom 16% (95% CI, 10-23) were alive after five years – quadruple the expected overall survival (OS) of patients who receive chemotherapy. The OS rates were similar between squamous (16%; 95% CI, 8-28; n=54) and non-squamous (15%; 95% CI, 8-25; n=74) NSCLC. Of the 16 long-term survivors, 9 were male and 7 were female. Expression of the PD-L1 biomarker does not completely account for the extended survival of the responding patients, as 7/10 evaluable patients had ≥1% PD-L1 expression and 3/10 had <1% expression. No further treatment was required in 75% (12/16) of the responding patients following completion of nivolumab treatment and there was no evidence of progressive disease.

Combination of Coxsackievirus A21 (CVA21) and ipilimumab shows promise in advanced melanoma

Preliminary data from the phase Ib MITCI trial were presented by Brendan Curti, MD, Providence Cancer Center. In this study, patients with advanced melanoma (n=26 to date) were treated with a novel combination of systemic ipilimumab (anti-CTLA-4) and intralesional CVA21. Patients were given 3x108 TCID50 CVA21 on study days 1, 3, 5, 8, and 22, then every three weeks. In addition, patients received four infusions of ipilimumab (3 mg/kg) every three weeks beginning on study day 22. Half of the evaluable patients (11/22) responded to the combination, four of whom achieved a complete response (CR). The objective response rate was 36% (4/11) in patients who had previously received immune checkpoint blockade and 64% (7/11) in checkpoint inhibitor-naïve patients. No dose-limiting toxicities have been reported and thus far, the overall grade 3/4 treatment-related adverse event (AE) rate is 8%.

Addition of IDO inhibition to pembrolizumab (anti-PD-1) improves treatment response in melanoma

Yousef Zakharia, MD, University of Iowa, presented results from an interim analysis of a phase II trial investigating the addition of an indoleamine 2,3-dioxygenase (IDO) inhibitor (indoximod) to standard of care immune checkpoint inhibitors approved for the treatment of advanced melanoma. The interim report is limited to patients who received pembrolizumab along with indoximod (n=60), which represent a majority of the patients enrolled. Concurrent with 3 mg/kg pembrolizumab every three weeks, patients received 1200 mg indoximod twice daily in 21 day cycles. Approximately half of the patients had received prior therapy. More than half of the patients (31/60) responded to treatment, with 25 partial responses (PR) and six patients achieving a CR. This combination was generally well tolerated with fatigue (60%), headache (33%), and nausea (32%) as the most common all-grade AE, although serious AE led to discontinuation of treatment for three patients.

Discussions

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