Phase 1b/2 Study (SCORES) assessing safety, tolerability, and preliminary anti-tumor activity of durvalumab plus AZD9150 or AZD5069 in patients with advanced solid malignancies and squamous cell carcinoma of the head and neck (SCCHN)

Cohen, Ezra E.W.; Hong, David S.; Draper, T. Wise; William, W.N.; Schrijvers, Dirk; Nin, R. Mesía; Scott, Martin; Lyne, Paul; Mugundu, Ganesh; McCoon, Patricia; Cook, Carl; Keilholz, Ulrich

doi:10.1093/annonc/mdx376.001

Cited by 17 publications

(15 citation statements)

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“…IO-IO: checkpoint + microenvironment/ immunometabolism(NCT02499328)Phase 1b/2. Durvalumab + AZD9150 (STATi) or AZD5069 (CX2i) in HNSCC patients.Metabolic competition exists between tumor and immune cells and there is evolving evidence that combining therapies that directly dampen tumor metabolism with immunotherapy could be a promising therapeutic strategy.A 25% ORR (5PR) was observed in patients with anti-PD-L1 treatment naïve R/M HNSCC patients, with responses observed in PD-L1+/− patients as well as HPV- patients [148]. Photoimmunotherapy(NCT02422979)Phase 2a.…”

Section: Key Clinical Questionsmentioning

confidence: 99%

The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of squamous cell carcinoma of the head and neck (HNSCC)

Cohen¹,

Bell²,

Bifulco³

et al. 2019

j. immunotherapy cancer

519

422

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Head and neck cancers, including those of the lip and oral cavity, nasal cavity, paranasal sinuses, oropharynx, larynx and nasopharynx represent nearly 700,000 new cases and 380,000 deaths worldwide per annum, and account for over 10,000 annual deaths in the United States alone. Improvement in outcomes are needed for patients with recurrent and or metastatic squamous cell carcinoma of the head and neck (HNSCC). In 2016, the US Food and Drug Administration (FDA) granted the first immunotherapeutic approvals – the anti-PD-1 immune checkpoint inhibitors nivolumab and pembrolizumab – for the treatment of patients with recurrent squamous cell carcinoma of the head and neck (HNSCC) that is refractory to platinum-based regimens. The European Commission followed in 2017 with approval of nivolumab for treatment of the same patient population, and shortly thereafter with approval of pembrolizumab monotherapy for the treatment of recurrent or metastatic HNSCC in adults whose tumors express PD-L1 with a ≥ 50% tumor proportion score and have progressed on or after platinum-containing chemotherapy. Then in 2019, the FDA granted approval for PD-1 inhibition as first-line treatment for patients with metastatic or unresectable, recurrent HNSCC, approving pembrolizumab in combination with platinum and fluorouracil for all patients with HNSCC and pembrolizumab as a single agent for patients with HNSCC whose tumors express a PD-L1 combined positive score ≥ 1. These approvals marked the first new therapies for these patients since 2006, as well as the first immunotherapeutic approvals in this disease. In light of the introduction of these novel therapies for the treatment of patients with head and neck cancer, The Society for Immunotherapy of Cancer (SITC) formed an expert committee tasked with generating consensus recommendations for emerging immunotherapies, including appropriate patient selection, therapy sequence, response monitoring, adverse event management, and biomarker testing. These consensus guidelines serve as a foundation to assist clinicians’ understanding of the role of immunotherapies in this disease setting, and to standardize utilization across the field for patient benefit. Due to country-specific variances in approvals, availability and regulations regarding the discussed agents, this panel focused solely on FDA-approved drugs for the treatment of patients in the U.S. Electronic supplementary material The online version of this article (10.1186/s40425-019-0662-5) contains supplementary material, which is available to authorized users.

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Section: Key Clinical Questionsmentioning

confidence: 99%

The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of squamous cell carcinoma of the head and neck (HNSCC)

Cohen¹,

Bell²,

Bifulco³

et al. 2019

j. immunotherapy cancer

519

422

View full text Add to dashboard Cite

show abstract

“…Early phase clinical trials in HNSCC patients have evaluated STAT3 inhibition using a decoy oligonucleotide (NCT00696176), a STAT3 antisense oligonucleotide AZD9150 (NCT02499328), and the small molecule inhibitor C188–9 (NCT03195699). The combination of AZD9150 and durvalumab was found to be well tolerated and induced a higher response rate than durvalumab monotherapy in patients with advanced solid malignancies including HNSCC [94]. In view of the critical role that IL-6/JAK/STAT3 signaling plays in the TME, investigation of combined treatment with IL-6/JAK/STAT3 inhibitors and immune checkpoint inhibitors is warranted.…”

Section: Scientific Rationalementioning

confidence: 99%

An update: emerging drugs to treat squamous cell carcinomas of the head and neck

Lee

Johnson

Grandis

2018

Expert Opinion on Emerging Drugs

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Introduction: Subsequent to the 2006 FDA approval of cetuximab, a variety of molecular targeting agents have been evaluated in head and neck squamous cell carcinoma (HNSCC). The treatment outcomes of recurrent and/or metastatic (R/M) HNSCC, in particular, remain dismal. The 2016 FDA approval of PD-1 immune checkpoint inhibitors has expanded the treatment options for R/M HNSCC, and highlights the potential for immune-based therapies. Areas covered: We will review the clinical application of EGFR-targeted agents, alone and in combination with other drugs. Molecular targeting agents directed against the IL6/PI3K/STAT3 signaling pathway will be covered. In addition, evaluation of immune checkpoint inhibitors in HNSCC, along with ongoing combination trials incorporating these agents, will be discussed. The expanded indications of emerging drugs and the potential clinical benefit of new drugs and treatment combinations will be summarized. Expert opinion: In recent years, there has been a major shift towards immunotherapy-based approaches for the treatment of HNSCC, leading to significant improvements in outcomes for a subset of patients. Leveraging the increased understanding of the genetic alterations that characterize individual HNSCC tumors will facilitate precision medicine approaches using targeted agents, immunotherapies, as well as standard chemotherapy and radiation.

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“…Prior data from a Phase 1b/2 study in patients with solid tumors indicate that a combined therapeutic approach targeting immunosuppression in the tumor bed (with J o u r n a l P r e -p r o o f danvatirsen) while promoting T-cell response (with durvalumab) could lead to improved efficacy. 18 Here, we report the results of the dose escalation and dose expansion phases of an open-label, Phase 1b multicenter trial to evaluate the safety, tolerability, efficacy, pharmacokinetics (PK) and immunogenicity of durvalumab as monotherapy and in combination with tremelimumab or danvatirsen in patients with relapsed or refractory DLBCL (NCT02549651).…”

Section: Resultsmentioning

confidence: 99%

A Phase 1b Study to Evaluate the Safety and Efficacy of Durvalumab in Combination With Tremelimumab or Danvatirsen in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Ribrag

Lee

Rizzieri

et al. 2021

Clinical Lymphoma Myeloma and Leukemia

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Phase 1b/2 Study (SCORES) assessing safety, tolerability, and preliminary anti-tumor activity of durvalumab plus AZD9150 or AZD5069 in patients with advanced solid malignancies and squamous cell carcinoma of the head and neck (SCCHN)

Cited by 17 publications

References 0 publications

The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of squamous cell carcinoma of the head and neck (HNSCC)

The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of squamous cell carcinoma of the head and neck (HNSCC)

An update: emerging drugs to treat squamous cell carcinomas of the head and neck

A Phase 1b Study to Evaluate the Safety and Efficacy of Durvalumab in Combination With Tremelimumab or Danvatirsen in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma

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