Trial in progress: Phase II study of stereotactic body radiation therapy and atezolizumab in the management of recurrent, persistent, or metastatic cervical cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS5596-TPS5596
Author(s):  
Kamran A. Ahmed ◽  
Youngchul Kim ◽  
Sachin M. Apte ◽  
Hye Sook Chon ◽  
Jing-Yi Chern ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Radiation Therapy ◽  
Phase Ii ◽  
Stereotactic Body Radiation Therapy ◽  
Objective Response ◽  
Primary Objective ◽  
Open Label ◽  
Recurrent Cervical Cancer ◽  
Stereotactic Body Radiation ◽  
Hypofractionated Radiation

TPS5596 Background: There is no consistent recommendation for management of metastatic cervical cancer beyond first line therapy with chemotherapy and bevacizumab. Pembrolizumab is now approved for PD-L1 positive or MSI-H/dMMR metastatic or recurrent cervical cancer. Numerous pre-clinical studies have provided evidence to combine radiation therapy with immune checkpoint inhibition to improve response rates. The evidence is strongest for short course, hypofractionated radiation regimens. We hypothesize treatment with atezolizumab with hypofractionated radiation therapy will improve objective response rate (ORR) compared with atezolizumab alone in patients with recurrent, persistent, or metastatic cervical cancer. Methods: The study is designed as a prospective, single arm, nonrandomized, open-label, phase II trial of stereotactic body radiation therapy (SBRT) with 24 Gy in 3 fractions to patients with ≥ 2 metastatic sites followed 1 week later by atezolizumab (1200 mg IV every 3 weeks) for patients with recurrent, persistent, or metastatic cervical cancer. Dose reductions will not be allowed. The primary objective of the study is to evaluate the ORR by Immune-Modified Response Evaluation Criteria in Solid Tumors (irRECIST) criteria following SBRT and atezolizumab. Secondary endpoints include progression free survival, overall survival, local control, and adverse events. Correlative aims include assessing blood and tissue biomarkers (i.e. PD-L1, mutation burden, TCR repertoire etc.) for association with clinical benefit. A total of 26 patients will be enrolled. An interim analysis will be performed to assess efficacy after 13 patients become evaluable.This study is open with 2 patients enrolled at the time of submission. Clinical trial information: NCT03614949.

scholarly journals Phase II study of atezolizumab in combination with bevacizumab in patients with advanced cervical cancer

2020 ◽  
Vol 8 (2) ◽  
pp. e001126
Author(s):  
Claire F Friedman ◽  
Alexandra Snyder Charen ◽  
Qin Zhou ◽  
Michael A Carducci ◽  
Alexandre Buckley De Meritens ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Phase Ii ◽  
Response Rate ◽  
Treatment Options ◽  
Objective Response ◽  
Primary Objective ◽  
Advanced Cervical Cancer ◽  
Open Label ◽  
Recurrent Cervical Cancer ◽  
Platinum Based Chemotherapy

BackgroundThere are limited treatment options for patients with metastatic or recurrent cervical cancer. Platinum-based chemotherapy plus the anti-vascular endothelial growth factor antibody bevacizumab remains the mainstay of advanced treatment. Pembrolizumab is Food and Drug Agency approved for programmed death ligand 1 (PD-L1) positive cervical cancer with a modest response rate. This is the first study to report the efficacy and safety of the PD-L1 antibody atezolizumab in combination with bevacizumab in advanced cervical cancer.MethodsWe report the results from a phase II, open-label, multicenter study (NCT02921269). Patients with advanced cervical cancer were treated with bevacizumab 15 mg/kg intravenous every 3 weeks and atezolizumab 1200 mg intravenous every 3 weeks. The primary objective was to measure the objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety.ResultsIn the total evaluable population (n=10), zero patients achieved an objective response as assessed by Response Evaluation Criteria In Solid Tumors (RECIST) V.1.1, resulting in a confirmed ORR of 0%. Of note, there were two patients who achieved an unconfirmed PR. The DCR by RECIST V.1.1 was 60% (0% complete response, 0% partial response, 60% stable disease). Median PFS was 2.9 months (95% CI, 1.8 to 6) and median OS was 8.9 months (95% CI, 3.4 to 21.9). Safety results were generally consistent with the known safety profile of both drugs, notably with two high-grade neurologic events.ConclusionsThe combination of bevacizumab and atezolizumab did not meet the predefined efficacy endpoint, as addition of bevacizumab to PD-L1 blockade did not appear to enhance the ORR in cervical cancer.

A phase I study of bintrafusp alfa (M7824) and NHS-IL12 (M9241) alone and in combination with stereotactic body radiation therapy (SBRT) in adults with metastatic non-prostate genitourinary malignancies.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS4599-TPS4599
Author(s):  
Scot Anthony Niglio ◽  
Daniel da Motta Girardi ◽  
Lisa M. Cordes ◽  
Lisa Ley ◽  
Marissa Mallek ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Phase I ◽  
Targeted Delivery ◽  
Immune Modulation ◽  
Stereotactic Body Radiation Therapy ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Open Label ◽  
Stereotactic Body Radiation ◽  
Cytokine Analysis

TPS4599 Background: The majority of non- prostate genitourinary (GU) cancers are lethal when metastatic and rare GU cancers have limited treatment options. Bintrafusp alfa is a bifunctional fusion protein composed of human TGF-β receptor II, which sequesters or “traps” all three TGF-β isoforms and a monoclonal PD-L1 antibody. NHS-IL12 is an immunocytokine composed of two IL-12 heterodimers, each fused to the H-chain of the NHS76 antibody. The NHS76 IgG1 antibody has affinity for both single- and double-stranded DNA (dsDNA) allowing for targeted delivery of pro-inflammatory cytokine, IL-12, to necrotic portions of tumor with DNA exposure to promote local immunomodulation. Preclinical data suggest synergy between these two agents. There is also evidence suggesting that stereotactic body radiation therapy (SBRT) can promote anti-tumor immune responses both locally and systemically while also synergizing with immune checkpoint inhibitors. Therefore, the combination of Bintrafusp alfa, NHS-IL12 and radiation is a potential strategy for metastatic non-prostate GU tumors. Methods: This is an open label, non-randomized, three-stage phase I trial of bintrafusp alfa and NHS-IL12 or bintrafusp alfa and NHS-IL12 in combination with either sequential or concurrent SBRT. Bintrafusp alfa (IV 1200 mg q2w) and SBRT (8 Gy x 3 fractions) are planned with a deescalating NHS-IL12 (subQ q4w) dose schedule. The accrual ceiling has been set at 66 patients. The trial will enroll patients with a pathologically confirmed diagnosis of metastatic non-prostate genitourinary cancer with an ECOG ≤ 2 (KPS ≥60%). Participants may have had prior cancer immunotherapy but excluding prior treatment with bintrafusp alfa and/or NHS-IL12. 9 patients will receive treatment in cycles consisting of 4 weeks. The primary objective is to determine the safety and highest tolerated doses with acceptable toxicity (recommended phase II dose) of bintrafusp alfa and NHS-IL12 alone or in combination with SBRT administered sequentially or concurrently in patients with metastatic non-prostate genitourinary cancers. Secondary objectives are objective response rate (ORR), progression free survival (PFS) and overall survival (OS). Exploratory objectives are to determine peripheral immune modulation and the status of the immune microenvironment using cytokine analysis, circulating tumor cells, multiplex immunohistochemistry, T-cell receptor sequencing, and RNA-sequencing. The study is open and enrolling. Clinical trial information: NCT04235777.

Excessive Toxicity When Treating Central Tumors in a Phase II Study of Stereotactic Body Radiation Therapy for Medically Inoperable Early-Stage Lung Cancer

2006 ◽  
Vol 24 (30) ◽  
pp. 4833-4839 ◽  
Author(s):  
Robert Timmerman ◽  
Ronald McGarry ◽  
Constantin Yiannoutsos ◽  
Lech Papiez ◽  
Kathy Tudor ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Radiation Therapy ◽  
Phase Ii ◽  
Local Control ◽  
Stereotactic Body Radiation Therapy ◽  
Early Stage ◽  
Stage I ◽  
Severe Toxicity ◽  
Stereotactic Body Radiation

PurposeSurgical resection is standard therapy in stage I non–small-cell lung cancer (NSCLC); however, many patients are inoperable due to comorbid diseases. Building on a previously reported phase I trial, we carried out a prospective phase II trial using stereotactic body radiation therapy (SBRT) in this population.Patients and MethodsEligible patients included clinically staged T1 or T2 (≤ 7 cm), N0, M0, biopsy-confirmed NSCLC. All patients had comorbid medical problems that precluded lobectomy. SBRT treatment dose was 60 to 66 Gy total in three fractions during 1 to 2 weeks.ResultsAll 70 patients enrolled completed therapy as planned and median follow-up was 17.5 months. The 3-month major response rate was 60%. Kaplan-Meier local control at 2 years was 95%. Altogether, 28 patients have died as a result of cancer (n = 5), treatment (n = 6), or comorbid illnesses (n = 17). Median overall survival was 32.6 months and 2-year overall survival was 54.7%. Grade 3 to 5 toxicity occurred in a total of 14 patients. Among patients experiencing toxicity, the median time to observation was 10.5 months. Patients treated for tumors in the peripheral lung had 2-year freedom from severe toxicity of 83% compared with only 54% for patients with central tumors.ConclusionHigh rates of local control are achieved with this SBRT regimen in medically inoperable patients with stage I NSCLC. Both local recurrence and toxicity occur late after this treatment. This regimen should not be used for patients with tumors near the central airways due to excessive toxicity.

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