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Nasser Hanna



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    FP01 - Early Stage/Localized Disease (ID 111)

    • Event: WCLC 2020
    • Type: Posters (Featured)
    • Track: Early Stage/Localized Disease
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      FP01.04 - BTCRC LUN19-396:  Adjuvant Chemotherapy Plus Atezolizumab in Stage IB-IIIA Resected NSCLC and Clearance of ctDNA (ID 3164)

      00:00 - 00:00  |  Author(s): Nasser Hanna

      • Abstract

      Introduction

      The vast majority of patients with stage IB - IIIA NSCLC are managed with upfront surgery, followed by 4 cycles of empiric adjuvant chemotherapy. However, many patients are cured with surgery alone and do not need any adjuvant therapy. While some patients require adjuvant therapy to achieve cure, the amount of adjuvant therapy necessary to achieve this goal is unknown. In order to optimize treatment, a predictive biomarker is needed to evaluate which patients benefit from adjuvant therapy and to personalize duration of treatment. Emerging data has evaluated the use of circulating tumor DNA (ctDNA) as a promising biomarker for early detection of minimal residual disease to predict risk of relapse. BTCRC LUN19-396 is a multicenter, phase II trial that aims to evaluate the role of concomitant chemotherapy and checkpoint inhibitor in the adjuvant setting for stage IB-IIIA resected NSCLC, and the clearance of ctDNA as a surrogate biomarker for long term disease free survival.

      Methods

      All patients with stage IB (tumors > 4cm), IIA, IIB, and select IIIA (T3N1, T4N0-1) resected NSCLC will be screened for study entry and will have ctDNA assessed within 60 days after surgery. All patients (regardless of whether they have detectable ctDNA after surgery) will be enrolled and treated with 4 cycles of cisplatin based chemotherapy plus concomitant atezolizumab, followed by up to 13 additional cycles of atezolizumab alone. Sequential analysis of ctDNA will be performed in all patients every 3 months until the end of treatment, up to 17 cycles at 13 months. The trial will enroll a total of 100 patients. The primary objective is to estimate the percentage of patients with detectable ctDNA after surgery who have clearance of ctDNA at designated time points during adjuvant therapy. The key secondary objective is to estimate the 1-year disease free survival in patients with undetectable ctDNA after 4 cycles of adjuvant chemotherapy plus atezolizumab who had detectable ctDNA after surgery. This trial opened to accrual in May 2020. Clinical trial information: NCT04367311

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    P01 - Antibody Drug Conjugates, Novel Therapeutics and Cytotoxics (ID 227)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Antibody Drug Conjugates, Novel Therapeutics and Cytotoxics
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P01.21 - ANSELMA: Antiangiogenic Second Line Lung Cancer Meta-Analysis on Individual Patient Data in Non-Small Cell Lung Cancer, Again Relevant in ICI Era (ID 721)

      00:00 - 00:00  |  Author(s): Nasser Hanna

      • Abstract

      Introduction

      There is renewed interest in the efficacy of 2nd line treatments (2LT) with anti-angiogenics (AA), now that immunotherapy plus chemotherapy (CT) is one of the standard options in 1st line treatment of advanced non-small cell lung cancer (NSCLC). Antibodies (mAb) against VEGF, VEGFR2, or AA tyrosine kinase inhibitors (TKI) have inconsistently shown benefit in combination with CT or erlotinib (E). We performed an individual patient data (IPD) meta-analysis to validate efficacy of these combinations as 2LT.

      Methods

      Randomized trials of AA plus standard 2LT (CT or TKI) compared to 2LT alone that ended accrual before 2015 were identified from publication databases, abstract proceedings and trial registers. Fixed-effect models were used to compute pooled hazard ratios (HRs) for overall survival (OS, primary endpoint), progression-free survival (PFS) and subgroup analyses. Peto method was used to estimate survival benefit.

      Results

      IPD were available for 15 out of 17 eligible trials (only via remote access for 9 trials). Out of 8,502 patients (pts) enrolled, 35% were female and 64% had adenocarcinoma. At 3 years, 10.5% were alive. Addition of AA significantly prolonged OS (HR=0.93 [95% confidence interval (CI): 0.89-0.98], p=0.005) and PFS (0.80 [0.77-0.84], p<0.0001) compared with 2LT alone. Absolute 1-year OS and PFS benefit for AA were +1.9% [95% CI: -0.3%;+4.1%] and +3.6% [+2.0%;+5.2%] respectively. According to the 3 types of combinations (mAb AA + CT, TKI AA + CT, AA + E), there was no significant interaction for OS. Interaction was significant for PFS (p=0.004): HR=0.78 [0.72-0.85], 0.86 [0.80-0.91] and 0.70 [0.63-0.77] respectively. There was a significant reduction of AA benefit on OS when age increased: 0.86 [0.75-0.99], 0.89 [0.81-0.97], 0.94 [0.87-1.02] and 1.04 [0.93-1.17] for pts <50, 50-59, 60-69 and ≥70 respectively (interaction p=0.009). Effect of AA was independent of sex (p=0.98) and performance status (0, ≥1; p=0.78) and ethnicity (Asian, non-Asian, p=0.38). Subgroup results were similar for PFS.

      Conclusion

      In the 2LT of advanced NSCLC, adding AA modestly but significantly prolongs OS and PFS. This appears independent of type of AA drugs, but the observed benefit may be higher in younger pts.

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    P03 - Early Stage/Localized Disease - Clinical Trials in Progress (ID 112)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Early Stage/Localized Disease
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P03.01 - A Randomized Phase II Trial of Adjuvant Pembrolizumab vs Observation after Curative Resection for Stage I NSCLC with Primary Tumors Between 1-4 cm (ID 3603)

      00:00 - 00:00  |  Author(s): Nasser Hanna

      • Abstract

      Introduction

      There are approximately 35,000 cases of stage I lung cancer in the United States each year. While these patients have better 5-year overall survival (OS) rates than their counterparts with locally advanced and metastatic disease, there is still considerable room for improvement. Based on a recent publication validating the 8th edition of the TNM classification, the 5-year OS for node-negative pathologically-staged NSCLC between 1-4cm ranges from 73-86%, and recurrence rates for resected stage I NSCLC can range from 18-38%. Previous studies looking at adjuvant chemotherapy in this setting have shown no benefit for stage IA tumors, and the current standard of care is observation alone. Checkpoint blockade with PD-1/PD-L1 inhibitors has shown considerable activity in NSCLC including in metastatic disease, as consolidation in stage III disease after chemoradiation, and in studies evaluating neoadjuvant immunotherapy. Given this activity and their favorable safety profile, we designed a study of adjuvant PD-1 inhibition following resection in stage I NSCLC.

      Methods

      This study is a randomized phase II multicenter trial of adjuvant Pembrolizumab versus observation alone following complete resection of stage I NSCLC with tumors between 1-4cm. The trial will enroll 368 patients randomized 1:1 to either Pembrolizumab 200mg IV every 3 weeks for up to 17 cycles or observation alone with scheduled CT scans and routine clinical follow-up. Stratification factors include PD-L1 TPS 50% vs. <50% and tumor size of 1-2cm vs. >2-4cm. The sample size is based on the hypothesis that adjuvant Pembrolizumab will increase 3-year disease free survival (DFS) from 75% to 84.15% (HR=0.6) with a power of 80% and a type I error of 0.1. The lead site is Indiana University, and the trial will be conducted through the Big Ten Cancer Research Consortium. The primary endpoint is DFS, and secondary endpoints include OS, DFS at 1-, 2-, and 3-year time points, and toxicity. The trial opened to accrual at the lead site in May 2020, and there are currently 2 patients enrolled.wclc 153 schema.png

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    P76 - Targeted Therapy - Clinically Focused - EGFR (ID 253)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Targeted Therapy - Clinically Focused
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P76.62 - RAMOSE: An Open-Label Randomized Phase II Study of Osimertinib with or without Ramucirumab in TKI-Naïve EGFR-Mutant Metastatic NSCLC (ID 3246)

      00:00 - 00:00  |  Author(s): Nasser Hanna

      • Abstract

      Introduction

      The third-generation EGFR tyrosine kinase inhibitor osimertinib is currently used as a standard first-line therapy for patients with metastatic EGFR-mutant NSCLC. However, a majority of patients’ cancers will develop resistance to osimertinib in less than 2 years, with a median progression-free survival of approximately 19 months.

      Preclinical models demonstrate upregulated VEGF signaling as a mechanism of acquired resistance to EGFR therapies, and improved efficacy when combining VEGF and EGFR inhibition. Ramucirumab, a monoclonal antibody targeting VEGF receptor 2, was recently approved by the US FDA in combination with erlotinib in patients with metastatic untreated EGFR-mutant NSCLC, based on a significant improvement in progression-free survival (PFS) with the combination seen in the RELAY trial.

      A phase I study of osimertinib with ramucirumab (NCT02789345) demonstrated safety and feasibility of this combination. With this strong preclinical and clinical evidence, we are conducting a phase 2 trial to evaluate the osimertinib ramucirumab combination’s efficacy in treatment-naïve EGFR-mutant NSCLC.

      Methods

      RAMOSE (HCRN LUN-18-335; NCT03909334) is a randomized, open-label phase 2 study comparing osimertinib 80mg PO daily + ramucirumab 10 mg/kg IV q3 weeks (O + R) to osimertinib 80mg PO daily monotherapy (O) for initial treatment of metastatic EGFR-mutant NSCLC. Patients are randomized 2:1 to the O+R versus O groups, with stratification based on type of EGFR mutation and presence of CNS metastasis. The trial plans to enroll total of 150 patients, allocating 100 to O+R and 50 to O monotherapy. The primary endpoint is PFS. Secondary endpoints include ORR, OS and DCR, as well as safety/toxicity. Major inclusion criteria include patients with metastatic NSCLC harboring activating EGFR mutations (L858R or Exon 19 del). Major exclusion criteria include prior anti-EGFR or anti-VEGF treatments. Patients with stable CNS metastasis are allowed. We hypothesize an improvement of PFS from 18.9 months to 29.7 months, corresponding to a hazard ratio of 0.65.

      The study is currently open at 9 sites in the USA, with additional sites planned. Hoosier Cancer Research Network is facilitating execution of the trial. Analysis by a study Data Safety Monitoring Board (DSMB) is performed annually. In addition, a planned interim analysis for efficacy will be performed after the first 75 subjects are enrolled.

      Results

      The trial opened to accrual in July 2019. As of July 02, 2020 (the data cutoff for planned DSMB analysis), 29 patients had been accrued. 25 of these patients were randomized (17 to O+R arm and 8 to O arm). Among the patients currently evaluable for toxicity (N=19), grade 3 or higher adverse events (AEs) were reported in 5/14 patients on O+R arm, versus 1/5 patients on O arm. In the O+R arm, grade 3 AEs included hypertension (n=1), pleural catheter infection (n=1), musculoskeletal pain (n=1), neutrophil count decreased (n=1), and dyspnea (n=1).

      Conclusion

      Early analysis from the RAMOSE trial shows no unexpected signals of toxicity with the combination of O+R. Enrollment for the trial is ongoing.