HOUSTON — Promising clinical results with combination treatments for patients with melanoma and lung cancer highlight immunotherapy advances being presented by researchers from The University of Texas MD Anderson Cancer Center at The Society for Immunotherapy of Cancer (SITC) 35th Anniversary Annual Meeting & Pre-Conference Programs (SITC 2020) .

«The SITC Annual Meeting provides us the opportunity to learn about and share groundbreaking new discoveries in tumor immunology and clinical advances for treating patients,» said Giulio Draetta, M.D., Ph.D., chief scientific officer. «As we strive to expand the use of immunotherapy for more patients, we look forward to seeing these results presented at this year’s meeting.»

Combination immunotherapy shows activity in metastatic melanoma (Abstract 420)

First-line treatment with a combination of nivolumab and interleukin-2 agonist bempegaldesleukin (BEMPEG) resulted in encouraging clinical activity for patients with metastatic melanoma in the Phase I/II PIVOT-02 trial. Results from the ongoing trial will be presented by Adi Diab, M.D., associate professor of Melanoma Medical Oncology.

Forty-one patients with previously untreated stage IV melanoma were enrolled on the trial, 38 of whom were able to be evaluated on the study. The treatment was well tolerated, as described in previous studies with this combination.

Twenty of the 38 efficacy evaluable patients (53%) had an overall response, or tumor shrinkage, and 13 (34%) had a complete response. Sixteen patients (80%) had ongoing responses and the median duration of response had not been reached at a follow-up of 29 months.

Median progression-free survival was 30.9 months, and median overall survival had not yet been reached.

«Despite the tremendous successes we have seen with immunotherapy in treating patients with advanced melanoma, current therapies are not effective for all patients. We have an unmet clinical need for new therapies that can provide prolonged benefit to more patients,» said Diab. «We are encouraged by the safety profile and durable responses seen with this combination therapy, and we look forward to continued evaluation in Phase III studies, which are enrolling now.»

Based on these results, the combination of BEMPEG and nivolumab was awarded Breakthrough Therapy designation by the U.S. Food and Drug Administration.

The study was supported by Nektar Therapeutics. A complete list of collaborating authors can be found within the abstract here.

Diab reports research support and consulting fees from both Nektar and Bristol Myers Squibb.

BEMPEG plus targeted therapy stimulates anti-tumor immune activation in advanced cancers (Abstract 368)

In the Phase I REVEAL trial for patients with advanced refractory solid tumors, combination treatment with BEMPEG and NKTR-262, a small-molecule agonist of Toll-like receptors (TLR) 7/8, led to activation of immune pathways associated with antitumor response. Results from the dose-escalation study will be presented by Diab.

NKTR-262 is designed to promote stimulation of an immune response in the tumor microenvironment, which can lead to antitumor activity when combined with BEMPEG in preclinical studies, explained Diab.

In 36 enrolled patients, the most frequent side effects were flu-like symptoms, fatigue, nausea and itching, all of which are consistent with the known safety profile of BEMPEG. One dose-limiting toxicity of elevated transaminase levels was observed at the highest dosage.

Two patients experienced partial responses, and seven patients had disease control (partial response or stable disease). Analysis of the immune response revealed increased activation of both T cells and natural killer (NK) cells in patients as well as of cytokines and interferon genes.

Based on these results, this combination will be evaluated in a Phase Ib dose-expansion with or without nivolumab for patients with advanced melanoma.

The study was supported by Nektar Therapeutics. A complete list of collaborating authors can be found within the abstract here.

Presurgical nivolumab and chemotherapy achieves high rates of tumor downstaging in patients with resectable lung cancer (Abstract 277)

Combining platinum-based doublet chemotherapy with nivolumab as a neoadjuvant, or presurgical, therapy for patients with stage I-IIIA non-small cell lung cancer (NSCLC) resulted in the highest rates of tumor downstaging at surgery, relative to other neoadjuvant regimens. Results of the study will be presented by Boris Sepesi, M.D., associate professor of Thoracic and Cardiovascular Surgery.

Patient cohorts on the study included 302 MD Anderson lung cancer patients treated with neoadjuvant platinum doublet chemotherapy and patients treated on the Phase II NEOSTAR study, led by Tina Cascone, M.D., Ph.D., assistant professor of Thoracic/Head & Neck Medical Oncology. NEOSTAR participants include 21 patients receiving nivolumab only, 16 patients receiving nivolumab plus ipilimumab and 22 patients receiving nivolumab with platinum doublet chemotherapy.

Among all cohorts, the combination of chemotherapy with nivolumab achieved the highest rates of clinical downstaging at 68%, compared to 38% in each additional cohort, a statistically significant difference.

«Maximizing the effectiveness of neoadjuvant therapy will help us to prevent relapse after surgery and improve outcomes for our patients,» said Sepesi. «The robust clinical downstaging rates seen after platinum doublet chemotherapy in combination with nivolumab are encouraging in patients with operable non-small cell lung cancer, and we look forward to learning if there are survival benefits in long-term follow-up data.»

This study was supported by Bristol Myers Squibb and MD Anderson’s Lung Cancer Moon Shot®, part of the institution’s Moon Shots Program®. A complete list of collaborating authors can be found within the abstract here.

Sepesi reports consulting fees from Bristol Myers Squibb and research support from Rexanna’s Foundation for Fighting Lung Cancer. Cascone reports consulting fees from MedImmune/AstraZeneca and Bristol Myers Squibb, and advisory role fees from EMD Serono and Bristol Myers Squibb and clinical research funding to MD Anderson Cancer Center from Boehringer Ingelheim, MedImmune/AstraZeneca, EMD Serono, and Bristol Myers Squibb.

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ABSTRACTS 277, 368, 420