Virtual Library

Start Your Search

Melissa L. Johnson



Author of

  • +

    MA04 - Novel Approaches with IO (ID 900)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Immunooncology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 13:30 - 15:00, Room 107
    • +

      MA04.01 - Cemiplimab, a Human Monoclonal Anti-PD-1, Alone or in Combination with Radiotherapy: Phase 1 NSCLC Expansion Cohorts (ID 13177)

      13:30 - 13:35  |  Author(s): Melissa L. Johnson

      • Abstract
      • Slides

      Background

      Cemiplimab (REGN2810), a human monoclonal anti-PD-1, has exhibited substantial antitumor activities in patients with advanced malignancies in a first-in-human study. We report interim results of the Phase 1 expansion cohorts (ECs 1 and 2) of cemiplimab, alone or plus radiotherapy, in advanced NSCLC (NCT02383212).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Patients with advanced NSCLC who had relapsed after, or were refractory to, at least, first-line therapy received cemiplimab 200 mg Q2W in EC 1, or cemiplimab 3 mg/kg Q2W plus radiotherapy (9 Gy × 3 times/week 1 week after first dose of cemiplimab) to a single lesion in EC 2. For EC 2, patients were required to have NSCLC for which palliative radiation therapy was indicated. Planned treatment duration was up to 48 weeks in both ECs. The co-primary objectives were to evaluate the safety, tolerability, and efficacy of cemiplimab, alone or plus radiotherapy. Tumor measurements (of non-irradiated lesions) were performed by RECIST 1.1 Q8W.

      4c3880bb027f159e801041b1021e88e8 Result

      As of Sept 1, 2017, 20 patients (13 M/ 7 F; median age 64.0 years [range, 50–82]) and 33 patients (22 M/ 11 F; median age 67.0 years [range, 47–82]) were enrolled in EC 1 and EC 2, respectively. ECOG performance status 1 versus 0 was 80.0% versus 20.0% and 66.7% versus 30.3%, respectively, for ECs 1 and 2, and missing in one in EC 2; 75.0% (EC 1) and 48.5% (EC 2) had received prior radiotherapy. Investigator-assessed overall response rate (ORR; complete response [CR] + partial response [PR]) was 40.0% (1 CR and 7 PRs) and 18.2% (6 PRs) in EC 1 and EC 2, respectively. Disease control rate (ORR + stable disease [SD]) was 60.0% (1 CR + 7 PRs + 4 SDs) and 72.7% (6 PRs + 18 SDs) in EC 1 and EC 2, respectively. The most common treatment-emergent adverse events (TEAEs) of any grade were arthralgia, asthenia, cough, and dyspnea (each 20.0%) in EC 1, and decreased appetite (30.3%), fatigue (27.3%), cough (24.2%), asthenia and back pain (each 21.2%) in EC 2. Grade ≥3 TEAEs occurring in ≥2 patients were pneumonia (10.0%) in EC 1; and anemia (12.1%), hypophosphatemia and urinary tract infection (each 6.1%) in EC 2. One patient in EC 2 experienced TEAE of pneumonitis with an outcome of death, considered related to study drug.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Cemiplimab monotherapy demonstrated substantial antitumor activity in pretreated NSCLC patients. The safety profiles were comparable with other anti-PD-1 agents and radiotherapy.

      6f8b794f3246b0c1e1780bb4d4d5dc53

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    MA05 - Improving Outcomes in Locoregional NSCLC II (ID 901)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Treatment of Locoregional Disease - NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 13:30 - 15:00, Room 105
    • +

      MA05.01 - E6508: Phase II Study of Immunotherapy with Tecemotide and Bevacizumab after Chemoradiation in Unresectable Stage III NS-NSCLC (ID 13853)

      13:30 - 13:35  |  Author(s): Melissa L. Johnson

      • Abstract
      • Presentation
      • Slides

      Background

      Chemoradiation (CRT) is standard of care for unresectable stage III NSCLC. Tecemotide is a MUC1 antigen-specific cancer immunotherapy. Bevacizumab is considered to have a significant role in immune modulation. Immunotherapy in combination with VEGF blockade was tested in this phase II trial combining tecemotide and bevacizumab in patients with stage III NS- NSCLC.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Subjects with stage III NS- NSCLC suitable for definitive CRT received carboplatin(C) AUC 2 + paclitaxel(P) 45 mg/m2 weekly + 66 Gy/33fx/6.5wk and consolidation C AUC 6 + P 225 mg/m2 q21 days x 2. Patients with CR/PR/SD were then registered onto Step 2 (S2). S2 was 6 weekly tecemotide injections followed by q6 weekly injections and bevacizumab 15 mg/kg q3 weeks for up to 34 doses. The primary endpoint was safety of tecemotide and bevacizumab after CRT and consolidation. The proportion of circulating dendritic cells and their expression of CD40, HLA-DR and CD123 (IL-3R) were analyzed by flow cytometry at various time points.

      4c3880bb027f159e801041b1021e88e8 Result

      70 patients were enrolled from Dec 2010 to Oct 2014; 68 started therapy, and 39 completed CRT and consolidation therapy. Reasons for discontinuation included progression (11) and toxicity (10). 33 patients were registered to S2. The median number of S2 cycles was 12 (range 2-34). S2 toxicity: gr 3 N=9 (6 hypertension), gr 4 N=1, gr 5 N=1. Among the treated and eligible patients (n=31), from study entry, the median PFS was 14.3 (95% CI 11.0-22.2), OS was 40.1 (95% CI 21.7-NA) months. A correlative trend of increased expression of CD40 and HLA-DR on CD11c+ cells was observed at cycle 7 (week 21) of S2.

      e6508.patel.png

      8eea62084ca7e541d918e823422bd82e Conclusion

      This cooperative group trial met its endpoint, demonstrating tolerability of tecemotide and bevacizumab after CRT and consolidation in NS-NSCLC pts. In this select group of patients, therapy with tecemotide and bevacizumab was associated with encouraging PFS and OS.

      6f8b794f3246b0c1e1780bb4d4d5dc53

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    MA08 - Clinical Trials in Brain Metastases (ID 906)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Advanced NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 15:15 - 16:45, Room 203 BD
    • +

      MA08.05 - Brain Penetration of Lorlatinib and Cumulative Incidence Rates for CNS and Non CNS Progression from a Phase 1/2 Study (ID 12760)

      15:45 - 15:50  |  Author(s): Melissa L. Johnson

      • Abstract
      • Presentation
      • Slides

      Background

      The potent, selective, third-generation ALK/ROS1 tyrosine kinase inhibitor (TKI) lorlatinib was designed to penetrate the blood-brain barrier (BBB). In a phase 1/2 study, lorlatinib showed robust clinical activity in patients with ALK-positive non-small cell lung cancer (NSCLC), most of whom had CNS metastases and failed ≥1 ALK TKI. In preclinical studies, lorlatinib demonstrated high BBB permeability with rapid brain uptake in vivo and significant activity against ALK-positive intracranial tumor models.1,2 To assess brain penetration of lorlatinib in a clinical setting, we report exploratory analyses from a phase 1/2 study (NCT01970865), evaluating CSF-to-plasma concentration ratios from a small sample of patients and cumulative incidence rates (CIRs) of CNS progression, non-CNS progression and deaths for pretreated patients with ALK-positive NSCLC ± baseline CNS metastases.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Across the ongoing phase 1/2 study, 5 patients at lorlatinib 100 mg QD starting dose underwent CSF sampling. Patients with ALK-positive NSCLC with ≥1 prior ALK TKI were analysed for progressive disease, categorized as either CNS or non-CNS progression, based on independent central review. CIRs for patients in expansion cohorts EXP2–5 from the phase 2 portion of the phase 1/2 study (N=198) were calculated using competing risks methodology.

      4c3880bb027f159e801041b1021e88e8 Result

      In patients (n=5), mean CSF-to-plasma concentration ratio was 0.73 (SD 0.14). The table shows CIRs at 6 and 12 months.

      Months Cumulative Incidence Probability
      Patients with ≥1 prior ALK TKIa CNS Progression

      Non-CNS

      Progression

      Death
      All patients (n=198)

      6 mos

      12 mos

      0.13

      0.18

      0.25

      0.37

      0.05

      NE
      Patients with baseline CNS metastases (n=131)

      6 mos

      12 mos

      0.14

      0.22

      0.21

      0.31

      NE

      NE
      Patients with no baseline CNS metastases (n=67)

      6 mos

      12 mos

      NE

      NE

      0.32

      0.49

      0.05

      NE

      aPatients in expansion cohorts EXP2–5 from the phase 2 study

      NE, not evaluable
      8eea62084ca7e541d918e823422bd82e Conclusion

      Lorlatinib showed high BBB permeability as evidenced by a high mean CSF-to-plasma concentration ratio, in line with preclinical rat studies showing CNS penetration. This translated into high activity against CNS metastases as suggested by the numerically higher probability of the first progression event being extracranial rather than intracranial, including in patients with a history of CNS metastases.

      References

      1. Collier, et al. Mol Imaging 2017;16:1–3.

      2. Zou, et al. Cancer Cell 2015;28:70–81.

      6f8b794f3246b0c1e1780bb4d4d5dc53

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    OA02 - Novel Therapies in ROS1, HER2 and EGFR (ID 893)

    • Event: WCLC 2018
    • Type: Oral Abstract Session
    • Track: Targeted Therapy
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 10:30 - 12:00, Room 105
    • +

      OA02.05 - CK-101 (RX518), a Third Generation Mutant-Selective Inhibitor of EGFR in NSCLC: Results of an Ongoing Phase I/II Trial (ID 11982)

      11:15 - 11:25  |  Presenting Author(s): Melissa L. Johnson

      • Abstract
      • Presentation
      • Slides

      Background

      CK-101 (also known as RX518) is a novel, oral, third-generation, irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that selectively inhibits both EGFR-TKI-sensitizing and resistance mutations, with minimal activity on wild-type EGFR. CK-101 is being studied in an ongoing first-in-human, multicenter, Phase I/II trial in advanced non-small cell lung cancer (NSCLC) patients (pts) with EGFR mutations and other advanced malignancies in the US, Australia, New Zealand and Thailand (NCT02926768). Following dose escalation in which 18 pts received CK-101 in dose groups ranging from 100 mg to 1200 mg/day, a first dose-expansion cohort was enrolled at 400 mg bid.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Eligible pts in dose escalation had a confirmed diagnosis of NSCLC or any advanced solid tumor where targeting EGFR was reasonable. Eligible pts in dose-expansion had a confirmed diagnosis of either (1) EGFR mutation-positive advanced or metastatic NSCLC without prior exposure to EGFR-TKI therapy, or (2) T790M-positive advanced or metastatic NSCLC with disease progression on previous EGFR-TKI therapy, with no limit on number of prior lines of systemic therapy.

      4c3880bb027f159e801041b1021e88e8 Result

      As of 25 June 2018, 37 pts were treated in dose escalation and expansion and evaluable for safety; median age 59 years, 51% male, 51% Asian, 84% ECOG PS 1. No DLTs or treatment-related SAEs were reported. Most common treatment-emergent adverse events: nausea (16%), diarrhea (14%), lacrimation increased (14%) and vomiting (11%), all grade 1/2 except one grade 3 diarrhea; no grade 4. In dose-expansion, 19 pts were treated with CK-101 at a dose of 400 mg bid and evaluable for response; 8/19 (42%) pts were treatment-naïve, 6/19 (32%) pts had brain metastases; 16/19 (84%) pts remained on treatment. Disease control rate was 100% (19/19), with 16/19 pts (84%) experiencing target lesion reduction versus baseline and 8 pts achieving a partial response (7 confirmed, 1 pending confirmation). In treatment-naïve pts, 6/8 (75%) pts achieved a partial response. In pts with brain metastases, 3/6 (50%) pts achieved a partial response. Higher drug exposures were associated with higher response rate with a confirmed ORR of 55% (6/11) in pts achieving Cmax >400 ng/mL. Median duration of response and progression-free survival were not reached as of the data cutoff.

      8eea62084ca7e541d918e823422bd82e Conclusion

      CK-101 was well tolerated with a manageable safety profile. Durable anti-tumor activity was observed, particularly in treatment-naïve pts. Further study is ongoing to establish the optimal dose to maximize therapeutic effect in a planned Phase 3 study in treatment-naïve EGFR-mutant NSCLC pts.

      6f8b794f3246b0c1e1780bb4d4d5dc53

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    OA12 - Novel Therapies in MET, RET and BRAF (ID 921)

    • Event: WCLC 2018
    • Type: Oral Abstract Session
    • Track: Targeted Therapy
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 15:15 - 16:45, Room 106
    • +

      OA12.07 - Clinical Activity of LOXO-292, a Highly Selective RET Inhibitor, in Patients with RET Fusion+ Non-Small Cell Lung Cancer (ID 13922)

      16:20 - 16:30  |  Author(s): Melissa L. Johnson

      • Abstract
      • Presentation
      • Slides

      Background

      RET kinase gene fusions are actionable drivers that occur in ~2% of non-small cell lung cancers (NSCLC). However, the clinical activity of multikinase inhibitors (MKIs) with anti-RET activity in RET fusion+ NSCLC patients has been limited. LOXO-292 is a highly selective RET inhibitor, with preclinical activity against diverse RET fusions, potential acquired resistance mutations, and against brain metastases.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      LIBRETTO-001 is a multicenter global phase 1/2 study (26 sites, 9 countries) enrolling patients w/ advanced solid tumors (NCT03157128) including RET fusion+ NSCLC. Patients are dosed orally in 28-day cycles with dose escalation following a 3+3 design. The primary endpoint is MTD/recommended dose determination. Secondary endpoints include safety, overall response rate (ORR, RECIST 1.1) and duration of response (DoR). Initial data were presented at the ASCO 2018 Annual Meeting.

      4c3880bb027f159e801041b1021e88e8 Result

      As of 02-April 18, 82 solid tumor patients (including 38 RET fusion+ NSCLC) were treated at 8 doses (20 mg QD-240 mg BID). The MTD was not reached. AEs (≥10% of patients) were fatigue (20%), diarrhea (16%), constipation (15%), dry mouth (12%), nausea (12%), and dyspnea (11%); most were grade 1-2. 2 TEAEs ≥ grade 3 were attributed to LOXO-292 (Gr3 tumor lysis syndrome, Gr3 increased ALT). Of the 38 RET fusion+ NSCLC pts, 30 had at least 1 post-baseline assessment or discontinued LOXO-292 prior to such assessment. 26 of 30 patients (87%) had >20% radiographic tumor reduction (range: -21 to -72%). The ORR was 77% (23/30, 3 responses pending confirmation) with a confirmed ORR of 74% (20/27, excluding 3 patients with unconfirmed responses). The response rate was similar regardless of prior MKI treatment (12/15 MKI-naïve, 11/15 MKI pretreated). Responses occurred independent of upstream fusion partner when known (13/16 KIF5B vs 9/11 other) and included patients w/ baseline brain metastases. Most patients remained on treatment (33/38), including all responders. The median DoR was not reached (longest response was the first responder: >10+ months). Rapid plasma clearance of RET variants was observed, with complete clearance by day 15 in 10 of 17 (59%) NSCLC patients with assessable baseline and day 15 ctDNA.

      8eea62084ca7e541d918e823422bd82e Conclusion

      LOXO-292 was well-tolerated and had marked antitumor activity in RET-fusion+ NSCLC patients, including those w/ resistance to prior MKIs and brain metastases. Phase 2 cohorts are now open globally (160 mg BID). Updated safety and efficacy data as of 19 Jul 2018 will be presented.

      6f8b794f3246b0c1e1780bb4d4d5dc53

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    P2.13 - Targeted Therapy (Not CME Accredited Session) (ID 962)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 2
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
    • +

      P2.13-10 - Ph I/II Study of Oral Selective AXL Inhibitor Bemcentinib (BGB324) in Combination with Erlotinib in pts with EGFRm NSCLC   (ID 14272)

      16:45 - 18:00  |  Author(s): Melissa L. Johnson

      • Abstract

      Background

      Bemcentinib is a first-in-class, oral, selective AXL TKI which is being evaluated as a combination therapy across several phII clinical trials. Increased AXL expression is associated with innate immune suppression and the appearance of resistance to targeted therapies in models of NSCLC and pt samples. AXL inhibition via bemcentinib prevents the appearance of such resistance in vivo and has shown immunomodulatory effect in AML patients.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      This study was designed to confirm the safety and tolerability of bemcentinib as a monotherapy and when administered in combination with erlotinib (arm A). Pts with activating EGFR mutation driven NSCLC who had progressed on an approved EGFR inhibitor (arm B) or were receiving erlotinib in the first line setting (arm C) were treated with bemcentinib at RP2D in combination with full dose erlotinib to evaluate the potential of bemcentinib to reverse or prevent resistance to EGFR targeted therapy, respectively. Plasma protein biomarker levels were measured using the DiscoveryMap v3.3 panel (Myriad RBM) at C1D1 and C2D1.

      4c3880bb027f159e801041b1021e88e8 Result

      2 out of 8 pts (25%) with stage IV disease who received bemcentinib monotherapy achieved SD for close to 1 year including evidence of tumour shrinkage of 19% in 1 pt. 1 pt who had progressed on previous erlotinib monotherapy (12.5%) achieved a PR receiving bemcentinib in combination with erlotinib and remains on treatment well beyond 2 years later (arm A). A further 3 pts had SD at 6 wks. 11 patients (4 female, median age 58; 38-67) were enrolled in arm B and had received a median of 2 (1 - 4) previous lines of cytotoxic chemotherapy and a median of 2 previous EGFR inhibitors. 2 of these 11 pts (18%) including 1 pt who was refractory to erlotinib therapy at the onset of combination therapy remain on treatment more than 6 months into therapy at the time of writing with best responses of PR and SD, respectively. 1 further pt had SD at 6 weeks. The most common treatment-related AEs have been gastrointestinal and rash.There was no evidence of any impact of bemcentinib on erlotinib pharmacokinetics. Protein biomarkers predictive of pt benefit following bemcentinib treatment were identified.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Bemcentinib can be safely administered in combination with erlotinib to pts with NSCLC and achieves additional benefit in a proportion of patients who do not have T790M and have progressed on EGFR inhibition or are maintained on erlotinib alone. Clinical trial information: NCT02424617.

      6f8b794f3246b0c1e1780bb4d4d5dc53

    • +

      P2.13-43 - Phase 1 Study of the Anti-HER3 Antibody Drug Conjugate U3-1402 in Metastatic or Unresectable EGFR-Mutant NSCLC (ID 13484)

      16:45 - 18:00  |  Author(s): Melissa L. Johnson

      • Abstract
      • Slides

      Background

      While outcomes for patients with EGFR-mutant NSCLC have significantly improved with the use of EGFR tyrosine kinase inhibitors, there remain limited treatment options for many patients once they develop resistance to these agents. The HER3/ERBB3 oncogene is overexpressed in many cancers, including NSCLC, and higher expression is correlated with poor outcomes. U3-1402 is a novel HER3-targeting antibody-drug conjugate (ADC) comprised of a recombinant fully human anti-HER3 antibody (patritumab) covalently conjugated via a cleavable peptide linker to a derivative of the topoisomerase I inhibitor exatecan. After U3-1402 binds to HER3 on the tumor cell surface, it is internalized and leads to apoptosis via inhibition of topoisomerase I. This ADC achieves a high drug-to-antibody ratio (DAR) of ~8:1. In vivo xenograft mouse model studies with human tumor cell lines indicate that U3-1402 exhibits HER3 expression-dependent tumor growth inhibition activity.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      This is a multicenter Phase 1, Dose Escalation and Dose Expansion study of U3-1402 in metastatic or unresectable adenocarcinoma NSCLC subjects harboring EGFR-activating mutation who (a) are T790M mutation-negative after disease progression during treatment with erlotinib, gefitinib, or afatinib or (b) develop disease progression while on osimertinib. Eligible subjects are at least 18 years of age, have ECOG PS 0 or 1, have radiological documentation of disease progression while receiving continuous treatment with an EGFR TKI, have at least one measurable lesion per RECIST v1.1, have adequate bone marrow and organ function, do not have LVEF < 45%, do not have QTc prolongation, and do not have spinal cord compression or clinically active brain metastases. In Dose Escalation, subjects receive U3-1402 via intravenous infusion in 21-day cycles. In Dose Escalation, escalation of U3-1402 dosing is based on dose-limiting toxicity data in subjects, guided by the modified Continuous Reassessment Method (mCRM) using a Bayesian logistic regression model (BLRM) following the escalation with overdose control (EWOC) principle. Additionally, intra-subject dose escalation may be considered in subjects who have completed at least 4 cycles of treatment without ≥ Grade 2 treatment-emergent adverse events. In Dose Expansion, subjects receive U3-1402 at the recommended dose for expansion (RDE) determined in Dose Escalation. Primary objectives are to determine the safety, tolerability, and RDE of U3-1402. Secondary objectives are to assess the pharmacokinetic parameters of U3-1402 and its components, and to assess antitumor activity of U3-1402 (RECIST v1.1). Enrollment to Dose Escalation cohort 1 was completed in April 2018. Clinicaltrials.gov identifier: NCT03260491

      4c3880bb027f159e801041b1021e88e8 Result

      Section not applicable - CTIP

      8eea62084ca7e541d918e823422bd82e Conclusion

      Section no applicable

      6f8b794f3246b0c1e1780bb4d4d5dc53

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    PL02 - Presidential Symposium - Top 5 Abstracts (ID 850)

    • Event: WCLC 2018
    • Type: Plenary Session
    • Track: Advanced NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 08:15 - 09:45, Plenary Hall
    • +

      PL02.07 - IMpower 133: Primary PFS, OS and Safety in a PH1/3 Study of 1L Atezolizumab + Carboplatin + Etoposide in Extensive-Stage SCLC (ID 12892)

      09:00 - 09:10  |  Author(s): Melissa L. Johnson

      • Abstract
      • Presentation
      • Slides

      Background

      First-line (1L) standard-of-care treatment for extensive-stage small cell lung cancer (ES-SCLC) is platinum (carboplatin or cisplatin) with etoposide. Despite high initial response rates, there has been limited progress in the last two decades and outcomes remain poor with a median overall survival (OS) of ~10 months. IMpower133 (NCT02763579), a global Phase 1/3, double-blind, randomized, placebo-controlled trial evaluated efficacy and safety of adding atezolizumab, a humanized monoclonal anti–PD-L1 antibody, or placebo to 1L carboplatin and etoposide in ES-SCLC.

      Patients with measurable (RECIST v1.1) ES-SCLC, ECOG performance status 0 or 1, who had not received prior systemic treatment for ES-SCLC were enrolled. PD-L1 immunohistochemical testing was not required. Patients were randomized 1:1 to receive four 21-day cycles of carboplatin (AUC 5 mg/mL/min IV, Day 1) plus etoposide (100 mg/m2 IV, Days 1-3) with either atezolizumab (1200 mg IV, Day 1) or placebo, followed by maintenance therapy with atezolizumab or placebo until intolerable toxicity or progressive disease per RECIST v1.1. Patients meeting predefined criteria could receive treatment beyond progression. Co-primary endpoints were OS and investigator-assessed progression-free survival (PFS). Adverse events (AEs) were graded per NCI-CTCAE v4.0. Blood-based tumor mutation burden (bTMB) was assessed using prespecified cutoffs of ≥16 vs. <16 and ≥10 vs. <10 mutations/Mb.

      In total, 201 patients were randomized to the atezolizumab group, and 202 to the placebo group. Median follow-up was 13.9 months. Median OS was 12.3 months in the atezolizumab group and 10.3 months in the placebo group (hazard ratio [HR] 0.70 [95% confidence interval (CI): 0.54, 0.91; P=0.0069]). Median PFS was 5.2 months and 4.3 months, respectively (HR 0.77 [95% CI: 0.62, 0.96; P=0.017]). OS and PFS benefits were consistent across key patient subgroups. Investigator-assessed confirmed objective response rates were 60.2% and 64.4% in the atezolizumab and placebo groups, respectively; median duration of response, 4.2 and 3.9 months. Exploratory analyses showed OS survival benefits in subgroups above and below prespecified bTMB cutoffs. Grade 3-4 treatment-related AEs were reported in 56.6% vs. 56.1% patients in atezolizumab vs. placebo groups, respectively; serious treatment-related AEs occurred in 22.7% and 18.9% patients, respectively.

      Addition of atezolizumab to carboplatin and etoposide provided a significant improvement in OS and PFS in 1L ES-SCLC in an all-comer patient population. No unexpected safety signals were identified. Atezolizumab plus carboplatin and etoposide may represent a new standard regimen for patients with untreated ES-SCLC.

      a9ded1e5ce5d75814730bb4caaf49419

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    SH04 - Highlight of the Previous Day Sessions (ID 993)

    • Event: WCLC 2018
    • Type: Highlight of the Day Session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 07:00 - 08:00, Room 106
    • +

      SH04.01 - SCLC/NET (ID 14789)

      07:00 - 07:12  |  Presenting Author(s): Melissa L. Johnson

      • Abstract
      • Presentation

      Abstract not provided

      Information from this presentation has been removed upon request of the author.

      Information from this presentation has been removed upon request of the author.