scholarly journals 432 Nemvaleukin alfa, a novel engineered IL-2 cytokine, in combination with the anti-PD-1 antibody pembrolizumab in patients with recurrent/metastatic head and neck squamous cell carcinoma (ION-01 study)

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A462-A462
Author(s):  
Brian Gastman ◽  
Mac Cheever ◽  
Steven Fling ◽  
Cesar Perez ◽  
Manish Patel ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Partial Response ◽  
Combination Therapy ◽  
Adverse Events ◽  
Head And Neck ◽  
Stable Disease ◽  
Progressive Disease ◽  
Antitumor Effects ◽  
Antitumor Response ◽  
Best Response

BackgroundNemvaleukin alfa (nemvaleukin, ALKS 4230) is a novel engineered cytokine that selectively binds to the intermediate-affinity IL-2R to preferentially activate and expand anti-tumor CD8+ T and NK cells with minimal expansion of regulatory T cells (Treg), thereby leveraging antitumor effects of the IL-2 pathway while mitigating potential toxicity that limits use.1 Nemvaleukin single-agent activity has been demonstrated in checkpoint inhibitor-experienced patients, and deep and durable responses have been achieved in combination with pembrolizumab in multiple tumor types (eg, breast, head and neck, gastrointestinal, genitourinary, gynecological).2MethodsION-01 (NCT04144517) is a nonrandomized trial in adult patients with histologically/cytopathologically confirmed diagnosis of metastatic/recurrent head and neck squamous cell carcinoma. Eligible patients have progressive disease after ≥8 weeks on anti-PD-(L)1 therapy. The primary endpoint is the rate of new or improved antitumor response after the addition of nemvaleukin. Secondary objectives include characterization of the antitumor response and evaluation of safety and tolerability of the combination regimen. Patients receive intravenous nemvaleukin (3 μg/kg) once daily for the first 5 days and pembrolizumab (200 mg) on day 1 of each 21-day cycle. Tumor imaging and biopsies were performed at baseline and at pre-specified times. We present preliminary safety and antitumor activity (RECIST v1.1) data as of June 2021.ResultsFourteen patients with progressive disease received combination therapy with nemvaleukin and pembrolizumab; 8 had no prior response to pembrolizumab, 6 had previous best response of stable disease or partial response. Mean (± SD) age was 62 ± 12 years, 86% were male, and all were Caucasian. Prior anti-cancer therapy included radiotherapy (93%) and surgery (50%). ECOG performance status was 0 (14%) and 1 (86%) at baseline. Treatment-related adverse events of any grade in ≥30% of patients were chills (64.3%), pyrexia (57.1%), fatigue (42.9%), and nausea (35.7%). Five patients had stable disease as best response. One patient achieved a partial response (complete response in the target lesion) and remains on treatment (8+ cycles). Expansion of CD8+ T and NK cells with minimal Treg expansion was observed.ConclusionsNemvaleukin and pembrolizumab combination therapy was generally well tolerated; adverse events were consistent with those observed with intravenous nemvaleukin in ARTISTRY studies [2]. Peripheral immune cell expansion profiles are comparable to that observed with the same regimen in the ARTISTRY 1 phase 1 study. Emerging data from pretreatment and on-treatment paired biopsies will further characterize specific antitumor effects of nemvaleukin and pembrolizumab in this patient population.AcknowledgementsThe authors would like to thank all the patients who are participating in this study and their families. The study is sponsored by Alkermes, Inc. Medical writing and editorial support was provided by Parexel, and funded by Alkermes, Inc.Trial RegistrationClinicalTrials.gov NCT04144517ReferencesLopes JE, Fisher JL, Flick HL, et al. ALKS 4230: a novel engineered IL-2 fusion protein with an improved cellular selectivity profile for cancer immunotherapy. J Immunother Cancer 2020;8:e000673. doi: 10.1136/jitc-2020-000673.Boni V, Winer IS, Gilbert L, et al. ARTISTRY-1: Nemvaleukin alfa monotherapy and in combination with pembrolizumab in patients (pts) with advanced solid tumors. J Clin Oncol 2021;39(Suppl 15):abstr 2513.Ethics ApprovalThis study was approved by Quorum Review IRB (now Advarra IRB), approval number QR 33752.

Gefitinib for advanced cutaneous squamous cell carcinoma of head and neck: Phase II trial

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6054-6054 ◽  
Author(s):  
R. S. Weber ◽  
R. A. Lustig ◽  
A. K. El-Naggar ◽  
D. I. Rosenthal ◽  
E. S. Kim ◽  
...  
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
Protein Expression ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Stable Disease ◽  
Progressive Disease ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Egfr Gene ◽  
Correlative Studies

6054 Background: Advanced head and neck cutaneous squamous cell carcinoma (HN cSCC) carries a 30–40% risk of death by 2 years with standard therapies. Small molecular inhibitors of the epidermal growth factor receptor (EGFR) may have an impact. We evaluated gefitinib as an induction therapy in a high-risk patient (pt) group prior to definitive therapy to determine efficacy, toxicity and feasibility. Correlative studies of EGFR expression, gene mutation, and ploidy may serve as predictors of response. Methods: Eligible pts must have HN cSCC >2cm, regional nodal metastases, peri-neural invasion, or deep invasion and must be candidates for definitive locoregional therapy with surgery and/or radiation. Two 30-day induction cycles of gefitinib (250mg po qd). Pts are assessed clinically after 15 days. If a response is noted, gefitinib is continued. For pts with stable disease, the dose is escalated to 500mg qd. Pts with progressive disease go off study. Total and phosphorylated (p) EGFR protein expression was analyzed by immunohistochemistry and gene copy number by fluorescent in-situ hybridization (FISH). Results: To date, 23 pts are enrolled and 22 are evaluable for responses and toxicities. Complete responses (CR) were noted in 3 pts, partial response (PR) 7, stable disease (SD) 5, and progressive disease (PD) 7 (68.1% response per RECIST criteria). Minimal side effects are associated with gefitinib (cutaneous and GI related). EGFR and p-EGFR protein overexpression were observed in 5 of 11 (45.5%) pts tested thus far. Eight of the pts were FISH negative with respect to EGFR gene expression: 7 had low trisomy and 1 had low polysomy. Two were FISH positive and expressed high polysomy. No gene amplification was detected. No statistically significant correlations between EGFR gene or protein expression and responses to administration of gefitinib were found at this point in the analysis. Protein and gene expression analyses are ongoing. Conclusions: The preliminary results from our study are encouraging and suggest that anti-EGFR therapy may have a role in the adjuvant treatment of HN cSCC. Correlative studies may help identify pts most likely to respond to anti-EGFR therapy. No significant financial relationships to disclose.

scholarly journals Role of curcumin as an adjuvant in treatment of advanced head and neck squamous cell carcinoma

2018 ◽  
Vol 4 (6) ◽  
pp. 1388
Author(s):  
P. Arun ◽  
Sagayaraj A. ◽  
S. M. Azeem Mohiyuddin ◽  
D. Santosh
Keyword(s):  
Squamous Cell Carcinoma ◽  
Partial Response ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Stable Disease ◽  
Advanced Head ◽  
Group A ◽  
Group B

<p class="abstract"><strong>Background:</strong> Chemoradiation forms the major line of treatment in advanced head and neck squamous cell carcinoma, but the benefit of chemotherapeutic agents is at the expense of various toxicities. Curcumin has demonstrated promising results in in-vivo and in-vitro studies as a radiosensitiser. The objective of the study was to determine the role of curcumin as an adjuvant in patients undergoing chemo radiation for advanced head and neck cancers.</p><p class="abstract"><strong>Methods:</strong> Study involved 21 patients who underwent chemo radiotherapy for advanced head and neck cancers. They were randomized into two groups. Group A received 500 mg of curcumin while, Group B received placebo along with chemoradiation. The response was assessed using RECIST criteria at three months post treatment using contrast enhanced computerized tomography scan.  </p><p class="abstract"><strong>Results:</strong> Overall 58.3% patients had partial response and 41.7% patients had stable disease in group A. In group B, 33.3% patients had a partial response and 66.6% patient had a stable disease.</p><p class="abstract"><strong>Conclusions:</strong> Patients receiving curcumin along with chemoradiation had a marginal decrease in tumour volume and 58.3% patients had partial response and 41.7% had stable disease. A statistical significance could not be achieved due to lack of stage-match controls. Further studies are required to validate the role of curcumin as an adjuvant in the treatment of head and neck squamous cell carcinomas.</p>

scholarly journals Radiomics analysis for predicting pembrolizumab response in patients with advanced rare cancers

2021 ◽  
Vol 9 (4) ◽  
pp. e001752
Author(s):  
Rivka R Colen ◽  
Christian Rolfo ◽  
Murat Ak ◽  
Mira Ayoub ◽  
Sara Ahmed ◽  
...  
Keyword(s):  
Partial Response ◽  
Stable Disease ◽  
Progressive Disease ◽  
Tumor Response ◽  
Complete Response ◽  
Classification Model ◽  
P Value ◽  
Rare Cancer ◽  
Rare Cancers ◽  
Contrast Enhanced Ct

BackgroundWe present a radiomics-based model for predicting response to pembrolizumab in patients with advanced rare cancers.MethodsThe study included 57 patients with advanced rare cancers who were enrolled in our phase II clinical trial of pembrolizumab. Tumor response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and immune-related RECIST (irRECIST). Patients were categorized as 20 “controlled disease” (stable disease, partial response, or complete response) or 37 progressive disease). We used 3D-slicer to segment target lesions on standard-of-care, pretreatment contrast enhanced CT scans. We extracted 610 features (10 histogram-based features and 600 second-order texture features) from each volume of interest. Least absolute shrinkage and selection operator logistic regression was used to detect the most discriminatory features. Selected features were used to create a classification model, using XGBoost, for the prediction of tumor response to pembrolizumab. Leave-one-out cross-validation was performed to assess model performance.FindingsThe 10 most relevant radiomics features were selected; XGBoost-based classification successfully differentiated between controlled disease (complete response, partial response, stable disease) and progressive disease with high accuracy, sensitivity, and specificity in patients assessed by RECIST (94.7%, 97.3%, and 90%, respectively; p<0.001) and in patients assessed by irRECIST (94.7%, 93.9%, and 95.8%, respectively; p<0.001). Additionally, the common features of the RECIST and irRECIST groups also highly predicted pembrolizumab response with accuracy, sensitivity, specificity, and p value of 94.7%, 97%, 90%, p<0.001% and 96%, 96%, 95%, p<0.001, respectively.ConclusionOur radiomics-based signature identified imaging differences that predicted pembrolizumab response in patients with advanced rare cancer.InterpretationOur radiomics-based signature identified imaging differences that predicted pembrolizumab response in patients with advanced rare cancer.

scholarly journals Phase II Evaluation of Sorafenib in Advanced and Metastatic Squamous Cell Carcinoma of the Head and Neck: Southwest Oncology Group Study S0420

2010 ◽  
Vol 28 (20) ◽  
pp. 3330-3335 ◽  
Author(s):  
Stephen K. Williamson ◽  
James Moon ◽  
Chao H. Huang ◽  
Perry P. Guaglianone ◽  
Michael LeBlanc ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Adverse Events ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Phase Ii ◽  
Single Agent ◽  
Response Probability ◽  
Oncology Group ◽  
Southwest Oncology Group

Purpose We conducted a phase II trial to evaluate the efficacy and safety of single-agent sorafenib in chemotherapy-naïve patients with metastatic or recurrent squamous cell carcinoma of the head and neck (SCCHN). The primary end point was response probability (ie, confirmed complete and partial response [PR]). Patients and Methods Chemotherapy-naïve patients with metastatic, persistent, or recurrent SCCHN who received one induction or fewer or received an adjuvant chemotherapy regimen, who had adequate organ function, and who had a performance status ≤ 1 were eligible. Sorafenib was administered orally at 400 mg twice daily on a continuous basis in 28-day cycles. Responses were evaluated according to RECIST (Response Evaluation Criteria in Solid Tumors). Results Sorafenib was generally well tolerated. Of the 41 eligible patients assessed for adverse events, one experienced a grade 4 adverse event as a result of an asymptomatic pulmonary embolus. The most common grades 2 to 3 adverse events were fatigue, anorexia, stomatitis/oral pain, abdominal pain, hand-foot syndrome, weight loss, and hypertension. There was one confirmed PR and two unconfirmed PRs. The estimated confirmed response probability was 2% (95% CI, 0% to 13%). The estimated median progression-free survival was 4 months (95% CI, 2 to 4 months), and the estimated median overall survival was 9 months (95% CI, 7 to 14 months). Conclusion Sorafenib was well tolerated. Although response was poor, progression-free and overall survival times compare favorably with previous Southwest Oncology Group, phase II, single-agent trials.

scholarly journals Intratumoral Epidermal Growth Factor Receptor Antisense DNA Therapy in Head and Neck Cancer: First Human Application and Potential Antitumor Mechanisms

2009 ◽  
Vol 27 (8) ◽  
pp. 1235-1242 ◽  
Author(s):  
Stephen Y. Lai ◽  
Priya Koppikar ◽  
Sufi M. Thomas ◽  
Erin E. Childs ◽  
Ann Marie Egloff ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Head And Neck ◽  
Growth Factor Receptor ◽  
Maximum Tolerated Dose ◽  
Antitumor Effects ◽  
Best Response ◽  
Positron Emission ◽  
Epidermal Growth

Purpose Squamous cell carcinoma of the head and neck (SCCHN) is characterized by upregulation of the epidermal growth factor receptor (EGFR). We developed a novel strategy to target EGFR by using a therapeutic gene that consisted of an EGFR antisense (AS) gene sequence under U6 promoter control. A phase I clinical trial was conducted to evaluate the safety and biologic effects of EGFR AS. Patients and Methods Patients with advanced SCCHN who were refractory to standard therapies and who had at least one assessable and accessible lesion were enrolled. The EGFR AS dose was escalated in successive cohorts (six dose levels; 60 to 1,920 μg/injection). Patients received four weekly intratumoral EGFR AS injections. Tumor biopsies were performed before and after completion of therapy. Treatment response was assessed by tumor volume measurements (positron emission tomography/computed tomography), and levels of target proteins were assessed by immunohistochemistry. Results Seventeen assessable patients were treated. No grades 3 to 4 or dose-limiting toxicities were noted, and a maximum-tolerated dose was not reached. Five patients (29%) achieved a clinical response, which included two complete responses (CRs) and three partial responses (PRs); two additional patients had stable disease (SD) as the best response. Patients with disease control (CR + PR + SD) had tumors with higher EGFR and lower STAT3 expression at baseline compared with patients who had progressive disease (P = .0312 and P = .095, respectively). Conclusion Intratumoral EGFR AS was safe and resulted in antitumor activity in patients with advanced SCCHN. Baseline levels of high EGFR and low STAT3 may be associated with antitumor effects.

scholarly journals Management of Advanced Medullary Thyroid Carcinoma with Vandetanib: Case Series

2021 ◽  
Vol 5 (1) ◽  
pp. 01-07
Author(s):  
Andrés Flórez R
Keyword(s):  
Partial Response ◽  
Adverse Events ◽  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Stable Disease ◽  
Case Series ◽  
Medullary Thyroid ◽  
The Mean ◽  
Grade 3

Objective: To describe the tumor response and adverse events in patients with advanced medullary thyroid carcinoma (MTC) treated with vandetanib at the National Cancer Institute in Bogotá, Colombia. Materials and Methods: Case series including five patients with advanced MTC treated with vandetanib from April 2011 to August 2018 and a minimum follow-up of 6 months. Results: 5 patients met the inclusion criteria, including 3 women. The mean age was 49 years. A total of 4 patients underwent total thyroidectomy prior to starting vandetanib. The main indication for vandetanib was progression of liver metastasis (4 patients). Regarding treatment response, 3 patients presented stable disease, 1 patient showed partial response, and 1 had disease progression. The mean treatment duration was 16.5 months. Grade 3 or 4 adverse events were observed in three patients, 1 with diarrhea, 1 with hypertension, and 1 with rash. All symptoms improved with dose reduction or temporary suspension of vandetanib. Conclusions: The management of advanced MTC with vandetanib allows for prolonged disease control (stable disease or partial response). Although adverse events are frequent, most are mild and severe cases are manageable.

scholarly journals Phase I Trial of Copanlisib, a Selective Pi3k Inhibitor, in Combination With Cetuximab in Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Grégoire Marret ◽  
Nicolas Isambert ◽  
Keyvan Rezai ◽  
Jocelyn Gal ◽  
Esma Saada-Bouzid ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Phase I ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Maximum Tolerated Dose ◽  
Pi3k Inhibitor ◽  
Neck Squamous Cell Carcinoma ◽  
Best Response ◽  
Disease Stabilization

Abstract BackgroundThe phosphatidylinositol-3 kinase pathway is often altered in head and neck squamous cell carcinoma (HNSCC), and is involved in the resistance to EGFR inhibitors. ObjectiveWe investigated the dose-limiting toxicities (DLTs), maximum tolerated dose, pharmacokinetics, and preliminary efficacy of the combination of copanlisib, an intravenous, pan-class I PI3K inhibitor, with the anti-EGFR monoclonal antibody cetuximab in recurrent and/or metastatic HNSCC patients in a phase I dose-escalation trial. Patients and methodsCopanlisib was given intravenously on days 1, 8, and 15 of 28-day cycles at the dose of 45 mg and 30 mg, in combination with standard doses of weekly cetuximab (400 mg/m² loading dose followed by 250 mg/m² on days 8, 15, and 22, and weekly thereafter). ResultsThree patients received copanlisib 45 mg, of whom two experienced grade 3 hyperglycemia during Cycle 1 that met the DLT criteria. Eight patients were then treated with copanlisib at the dose of 30 mg. Because of the occurrence of hyperglycemia, a premedication with metformine was introduced on the day of the injections. No DLTs were reported at this dose level. The trial was stopped early because of the unfavourable toxicity profile of the combination. Among eight evaluable patients for response, four patients (50%) had disease stabilization according to RECIST1.1 as best response.ConclusionCopanlisib combined with cetuximab demonstrated unfavorable toxicity and limited efficacy in heavily pretreated recurrent and/or metastatic HNSCC patients. NCT02822482, Date of registration: June 2016.

scholarly journals Clinical Outcomes of Cetuximab and Paclitaxel after Progression on Immune Checkpoint Inhibitors in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Medicina ◽  
2021 ◽  
Vol 57 (11) ◽  
pp. 1151
Author(s):  
Shinsuke Suzuki ◽  
Satoshi Toyoma ◽  
Yohei Kawasaki ◽  
Koh Koizumi ◽  
Nobuko Iikawa ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Adverse Events ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Neck Squamous Cell Carcinoma ◽  
Grade 3

Background and Objectives: In recent years, the effectiveness of chemotherapy after immune checkpoint inhibitor administration has attracted attention in various cancers, including head and neck cancers. However, individual assessments of the administered chemotherapy regimens are insufficient. This study aimed to evaluate the efficacy and safety of chemotherapy after immune checkpoint inhibitor administration in recurrent metastatic head and neck cancer by focusing on a single regimen. Materials and Methods: We retrospectively reviewed clinical and radiological data from the medical records of 18 patients with recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) who received systemic chemotherapy with weekly cetuximab and paclitaxel (Cmab + PTX) after progression following immune checkpoint inhibitor (ICI) therapy. The objective response rate (ORR) and disease control rate (DCR) were assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Adverse events (AEs) were recorded using National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Results: In all patients, the ORR, DCR, median PFS, and median OS were 44.4%, 72.2%, 3.8 months, and 9.6 months, respectively. Regarding AEs, three patients developed grade 3 neutropenia. Grade 3 anemia, paronychia, asthenia, and peripheral neuropathy were observed in one patient each. There were no treatment-related deaths. Conclusions: Cmab + PTX was shown to maintain high efficacy and acceptable safety for R/M HNSCC that progressed after ICI therapy. Further research is needed to establish optimal treatment sequences and drug combinations for recurrent R/M HNSCC.

Open-Label, Uncontrolled, Multicenter Phase II Study to Evaluate the Efficacy and Toxicity of Cetuximab As a Single Agent in Patients With Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck Who Failed to Respond to Platinum-Based Therapy

2007 ◽  
Vol 25 (16) ◽  
pp. 2171-2177 ◽  
Author(s):  
Jan B. Vermorken ◽  
José Trigo ◽  
Ricardo Hitt ◽  
Piotr Koralewski ◽  
Eduardo Diaz-Rubio ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Combination Therapy ◽  
Disease Control ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Disease Progression ◽  
Response Rate ◽  
Single Agent ◽  
Open Label ◽  
Metastatic Squamous Cell Carcinoma

PurposeTo evaluate the efficacy and safety of the epidermal growth factor receptor–directed monoclonal antibody cetuximab administered as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) who experience disease progression on platinum therapy.Patients and MethodsAn open-label multicenter study in which patients with disease progression on two to six cycles of platinum therapy received single-agent cetuximab (initial dose 400 mg/m2followed by subsequent weekly doses of 250 mg/m2) for ≥ 6 weeks (single-agent phase). Patients who experienced disease progression could receive salvage therapy with cetuximab plus platinum (combination-therapy phase). From June 2001 to December 2002, 103 patients were enrolled and treated with cetuximab, 53 of whom subsequently received combination therapy.ResultsIn the single-agent phase, response rate was 13%, disease control rate (complete response/partial response/stable disease) was 46%, and median time to progression (TTP) was 70 days. During the combination-therapy phase, the objective response rate was zero, disease control rate was 26%, and TTP was 50 days. Median overall survival was 178 days. Treatment was well tolerated. The most common cetuximab-related adverse events in the single-agent phase were skin reactions, particularly rash (49% of patients, mainly grade 1 or 2). There was one treatment-related death due to an infusion-related reaction.ConclusionSingle-agent cetuximab was active and generally well tolerated in the treatment of recurrent and/or metastatic SCCHN that progressed on platinum therapy. Response was comparable to that seen with cetuximab plus platinum combination regimens in the same setting.

Phase II Trial of Intratumoral Administration of ONYX-015, a Replication-Selective Adenovirus, in Patients With Refractory Head and Neck Cancer

2001 ◽  
Vol 19 (2) ◽  
pp. 289-298 ◽  
Author(s):  
J. Nemunaitis ◽  
F. Khuri ◽  
I. Ganly ◽  
J. Arseneau ◽  
M. Posner ◽  
...  
Keyword(s):  
Head And Neck ◽  
Phase Ii ◽  
Stable Disease ◽  
Progressive Disease ◽  
Phase Ii Trial ◽  
Intratumoral Injection ◽  
Antitumoral Activity ◽  
Complete Regression ◽  
Standard Regimen ◽  
Disease Rates

PURPOSE: To determine the safety, humoral immune response replication, and activity of multiple intratumoral injections of ONYX-015 (replication selective adenovirus) in patients with recurrent squamous cell carcinoma of the head and neck (SCCHN).PATIENTS AND METHODS: This phase II trial enrolled patients with SCCHN who had recurrence/relapse after prior conventional treatment. Patients received ONYX-015 at a dose of 2 × 1011particles via intratumoral injection for either 5 consecutive days (standard) or twice daily for 2 consecutive weeks (hyperfractionated) during a 21-day cycle. Patients were monitored for tumor response, toxicity, and antibody formation.RESULTS: Forty patients (30 standard and 10 hyperfractionated) received 533 injections of ONYX-015. Standard treatment resulted in 14% partial to complete regression, 41% stable disease, and 45% progressive disease rates. Hyperfractionated treatment resulted in 10% complete response, 62% stable disease, and 29% progressive disease rates. Treatment-related toxicity included mild to moderate fever (67% overall) and injection site pain (47% on the standard regimen, 80% on the hyperfractionated regimen). Detectable circulating ONYX-015 genome suggestive of intratumoral replication was identified in 41% of tested patients on days 5 and 6 of cycle 1; 9% of patients had evidence of viral replication 10 days after injection during cycle 1, and no patients had evidence of replication ≥ 22 days after injection.CONCLUSION: ONYX-015 can be safely administered via intratumoral injection to patients with recurrent/refractory SCCHN. ONYX-015 viremia is transient. Evidence of modest antitumoral activity is suggested.

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