Clinical activity and safety of anti-PD1 (BMS-936558, MDX-1106) in patients with advanced non-small-cell lung cancer (NSCLC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7509-7509 ◽  
Author(s):  
Julie R. Brahmer ◽  
Leora Horn ◽  
Scott Antonia ◽  
David R. Spigel ◽  
Leena Gandhi ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Response Duration ◽  
Tumor Burden ◽  
Clinical Activity ◽  
Ecog Performance Status ◽  
Activated T Cells ◽  
Platinum Based Chemotherapy ◽  
Previously Treated

7509 Background: BMS-936558 is a fully human mAb that blocks the programmed death-1 (PD-1) co-inhibitory receptor expressed by activated T cells. We report here that BMS-936558 mediates antitumor activity in heavily pretreated patients (pts) with advanced NSCLC, a tumor historically not considered to be responsive to immunotherapy. Methods: BMS-936558 was administered IV Q2WK to pts with various solid tumors, including NSCLC, at doses of 0.1 to 10 mg/kg during dose-escalation and/or cohort expansion. Pts with advanced NSCLC previously treated with at least 1 prior chemotherapy regimen were eligible. Pts received up to 12 cycles (4 doses/cycle) of treatment or until PD or CR. Clinical activity was assessed by RECIST 1.0. Results: Of 240 pts treated as of July 1, 2011, 75 NSCLC pts were treated at 1 (n=17), 3 (n= 19), or 10 mg/kg (n=39). ECOG performance status was 0/1/2 in 24/49/2 pts. Tumor histology was squamous (n=17), non-squamous (n=52), or unknown (n=6). The number of prior therapies was 1 (n=9), 2 (n=20), ≥3 (n=45), or unknown (n=1). Ninety-five percent of pts had received platinum-based chemotherapy and 40% had a prior tyrosine kinase inhibitor. Sites of metastatic disease included lymph node (n=50), liver (n=12), lung (n=62), and bone (n=13). Median duration of therapy was 10 wk (max 100 wk). Common related AEs were fatigue (17%), nausea (11%), pyrexia (7%), pruritus (7%), dizziness (7%), and anemia (7%). The incidence of grade 3-4 related AEs was 8%. There was 1 drug-related death due to pulmonary toxicity. Clinical activity was observed at all dose levels (Table) and in multiple histologies. Several pts had prolonged SD. Some had a persistent decrease in overall tumor burden in the presence of new lesions and were not categorized as responders. At the time of data lock, of 10 OR pts, 3 had responses lasting ≥6 mo and 5 were on study with response duration of 1.8-5.5 mo. Conclusions: BMS-936558 is well tolerated and has encouraging clinical activity in pts with previously treated advanced NSCLC. Further development of BMS-936558 in pts with advanced NSCLC is warranted. [Table: see text]

Clinical activity and safety of anti-PD-1 (BMS-936558, MDX-1106) in patients with advanced melanoma (MEL).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8507-8507 ◽  
Author(s):  
F. Stephen Hodi ◽  
Mario Sznol ◽  
David F. McDermott ◽  
Richard D. Carvajal ◽  
Donald P. Lawrence ◽  
...  
Keyword(s):  
Performance Status ◽  
Tumor Burden ◽  
Clinical Activity ◽  
Ecog Performance Status ◽  
Activated T Cells ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Previously Treated ◽  
Grade 3 ◽  
Dose Levels

8507 Background: BMS-936558 is a fully human mAb that blocks the programmed death-1 (PD-1) co-inhibitory receptor expressed by activated T cells. This study describes the activity and safety of BMS-936558 in patients (pts) with previously treated advanced MEL and underscores the importance of the PD-1/PD-L1 pathway in MEL therapy. Methods: BMS-936558 was administered IV Q2WK to pts with various solid tumors at doses of 0.1 to 10 mg/kg during dose-escalation and/or cohort expansion. Pts received up to 12 cycles (4 doses/cycle) of treatment or until PD or CR. Clinical activity was assessed by RECIST 1.0. Results: Of 240 pts treated as of July 1, 2011, 95 MEL pts were treated with BMS-936558 at 0.1 (n=13), 0.3 (n=17), 1 (n=28), 3 (n=17), or 10 mg/kg (n=20). ECOG performance status was 0/1/2 in 56/36/3 pts. The majority of pts (60/95) had received prior immunotherapy (IT), primarily interferon-alpha or IL-2 (prior anti-CTLA-4 excluded). Prior B-raf inhibitor therapy was noted in 7/95 pts. The number of prior therapies was 1 (n=35), 2 (n=34), or ≥3 (n=26). Sites of metastatic disease included lymph node (n=60), liver (n=32), lung (n=55), and bone (n=10). Median duration of therapy was 15 wk (max 120 wk), with 40 pts still receiving treatment. The incidence of grade 3-4 related AEs was 19% and included gastrointestinal (4%), endocrine (2%), and hepatobiliary disorders (1%). There were no drug-related deaths in MEL pts. Clinical activity was observed at all dose levels (Table). Of 20 pts with OR at the time of data lock, 12 had OR duration ≥1 yr and 6 pts were on study with OR duration between 1.9 and 11.3 mo. OR were seen in pts with visceral or bone metastases. Several pts had prolonged SD. Some had a persistent decrease in overall tumor burden in the presence of new lesions and were not categorized as responders. Conclusions: BMS-936558 had durable clinical benefit in pts with advanced MEL, including those who had received prior IT. Further development of BMS-936558 in MEL is ongoing. [Table: see text]

Clinical activity and safety of anti-PD-1 (BMS-936558, MDX-1106) in patients with previously treated metastatic renal cell carcinoma (mRCC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4505-4505 ◽  
Author(s):  
David F. McDermott ◽  
Charles G. Drake ◽  
Mario Sznol ◽  
Toni K. Choueiri ◽  
John Powderly ◽  
...  
Keyword(s):  
Performance Status ◽  
Human Monoclonal Antibody ◽  
Antiangiogenic Therapy ◽  
Progression Free Survival ◽  
Tumor Burden ◽  
Clinical Activity ◽  
Ecog Performance Status ◽  
Activated T Cells ◽  
Initial Portion ◽  
Previously Treated

4505 Background: BMS-936558 is a fully human monoclonal antibody that blocks the programmed death-1 co-inhibitory receptor (PD-1) expressed by activated T cells. In the initial portion of a phase I study, BMS-936558 showed promising activity in patients (pts) with various solid tumors, including mRCC. We expanded accrual in order to better characterize antitumor and dose effects. Methods: RCC pts were treated with BMS-936558 administered IV Q2WK at 10 mg/kg initially, followed by additional pts at 1 mg/kg. Pts received up to 12 cycles (4 doses/cycle) of treatment or until PD or CR. Clinical activity was assessed by RECIST 1.0. Results: Of 240 pts treated as of July 1 2011, 33 had mRCC and were treated at 1 (n=17) or 10 mg/kg (n=16). ECOG performance status was 0/1 in 13/19 pts. The number of prior therapies was 1 (n=10), 2 (n=9), or ≥3 (n=14), and included prior immunotherapy (n=20) or antiangiogenic therapy (n=24); 31 pts had prior nephrectomy. Sites of metastatic disease included lymph node (n=26), liver (n=7), lung (n=28), and bone (n=10). Median duration of therapy was 19 wk (max 96 wk). The incidence of grade 3-4 related AEs was 12% and included hypophosphatemia (6%), elevated ALT (3%), and cough (3%). Clinical activity was observed at both dose levels (Table). Some pts had a persistent reduction in overall tumor burden in the presence of new lesions and were not categorized as responders. Responses were noted in pts with visceral and bone metastases. Among the responders who were first treated ≥1 yr prior to data lock, 4 of 5 pts treated at 10 mg/kg had OR duration ≥1 yr, and 1 of 2 pts treated at 1 mg/kg was still on study with OR duration of 17.5 mo. Although the data for pts treated at 1mg/kg are not mature, the estimated progression-free survival (PFS) rate at 24 wk in pts receiving 10 mg/kg was 67% (Table). Conclusions: BMS-936558 is well tolerated and has durable clinical activity in pts with previously treated mRCC. Further development of BMS-936558 in pts with mRCC is ongoing. [Table: see text]

Clinical activity and safety of antiprogrammed death-1 (PD-1) (BMS-936558/MDX-1106/ONO-4538) in patients (pts) with previously treated, metastatic renal cell carcinoma (mRCC): An updated analysis.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 351-351 ◽  
Author(s):  
David F. McDermott ◽  
Charles G. Drake ◽  
Mario Sznol ◽  
Toni K. Choueiri ◽  
John D. Powderly ◽  
...  
Keyword(s):  
Performance Status ◽  
Human Monoclonal Antibody ◽  
Antiangiogenic Therapy ◽  
Complete Response ◽  
Clinical Activity ◽  
Response Patterns ◽  
Ecog Performance Status ◽  
Activated T Cells ◽  
Initial Portion ◽  
Previously Treated

351 Background: BMS-936558 is a fully human monoclonal antibody that blocks the PD-1 coinhibitory receptor expressed by activated T cells. In the initial portion of a phase I study (CA209-003), BMS-936558 showed promising activity in pts with various solid tumors, including mRCC. Accrual was expanded to better characterize antitumor, safety, and dose effects. Methods: Pts with RCC were treated with BMS-936558 IV q2wk at 10 mg/kg initially, followed by additional pts at 1 mg/kg. Pts received up to 12 cycles (4 doses/cycle) of treatment or until unacceptable toxicity, confirmed progressive disease, or complete response (CR). Clinical activity was assessed by RECIST v1.0. Results: As of July 3, 2012, 34 mRCC pts had been treated at 1 mg/kg (n=18) or 10 mg/kg (n=16). ECOG performance status was 0 in 13 pts and 1 in 21 pts. More than 40% of study patients received ≥3 prior therapies, >70% received prior antiangiogenic therapy, and >50% received prior immunotherapy. Sites of metastatic disease included lung (n=30), lymph node (n=28), bone (n=10), and liver (n=9). The incidence of grade 3-4 related adverse events was 21% and included hypophosphatemia (6%) and respiratory disorders (6%); there were no drug-related deaths among mRCC pts. Ongoing durable clinical responses were observed at both 1 and 10 mg/kg doses (Table) with some continuing off treatment. Three pts demonstrated nonconventional response patterns and were not categorized as responders by conventional RECIST. Current median duration of response was 12.9 months for both 1 and 10 mg/kg doses. Conclusions: BMS-936558 is tolerable and exhibits ongoing durable clinical activity in pts with previously treated mRCC. Clinical trial information: NCT00730639. [Table: see text]

Phase III trial of sitravatinib plus nivolumab vs. docetaxel for treatment of NSCLC after platinum-based chemotherapy and immunotherapy (SAPPHIRE).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS9635-TPS9635
Author(s):  
Ivor John Percent ◽  
Craig H. Reynolds ◽  
Kartik Konduri ◽  
Matthew Thomas Whitehurst ◽  
Emmanuel A. Nidhiry ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Prior Treatment ◽  
Phase Iii ◽  
Rank Test ◽  
Clinical Activity ◽  
Open Label ◽  
Ecog Performance Status ◽  
Platinum Based Chemotherapy

TPS9635 Background: Sitravatinib is an oral spectrum-selective tyrosine kinase inhibitor that targets the TAM (TYRO3/AXL/MERTK) and split (VEGFR2/KIT) family receptor tyrosine kinases (RTKs), as well as MET. Inhibition of TAM RTKs may promote the depletion of myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment (TME) and repolarize tumor associated macrophages towards the pro-inflammatory M1 phenotype. Inhibition of the split RTKs may reduce immunosuppressive regulatory T cells in addition to MDSCs within the TME. Given these pleiotropic immune-stimulating effects, sitravatinib may reverse resistance to checkpoint inhibitor therapy (CIT) and augment the antitumor immune response of nivolumab in patients (pts) with non-small cell lung cancer (NSCLC). An ongoing Phase 2 study (MRTX-500) demonstrates clinical activity of this combination in pts with metastatic non-squamous NSCLC after progression on or after CIT. Methods: Global, randomized, open-label, Phase 3 study of sitravatinib in combination with nivolumab vs docetaxel in pts with advanced non-squamous NSCLC who have progressed on or after CIT. Pts must have also received platinum-based chemotherapy either in combination with CIT or prior to CIT. Pts are randomized (1:1) to receive oral sitravatinib 120 mg once daily in continuous 28-day cycles combined with nivolumab IV 240 mg every 2 weeks or 480 mg every 4 weeks vs treatment with docetaxel 75 mg/m2 IV every 3 weeks. Patients are stratified based on number of prior treatment regimens in the advanced setting, ECOG performance status, and presence of brain metastases. Key eligibility criteria include duration of treatment of CIT of at least 4 months, discontinuation of prior treatment with CIT < 90 days prior to the date of randomization, and absence of symptomatic or uncontrolled brain metastases. The primary endpoint is overall survival (OS). Key secondary endpoints include safety and tolerability, ORR, PFS, PROs, and PK. OS will be analyzed using Kaplan-Meier methods and the stratified log-rank test to estimate and compare the median OS between the two treatment arms with 95% CI. An IDMC will review safety at regular intervals and efficacy at a planned interim analysis based on OS. Enrollment is ongoing. Clinical trial information: NCT03906071 .

CONTACT-01: A phase III, randomized study of atezolizumab plus cabozantinib versus docetaxel in patients with metastatic non-small cell lung cancer (mNSCLC) previously treated with PD-L1/PD-1 inhibitors and platinum-containing chemotherapy.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS9134-TPS9134
Author(s):  
Joel W. Neal ◽  
Palak Kundu ◽  
Tomohiro Tanaka ◽  
Ida Enquist ◽  
Sid Patel ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Randomized Study ◽  
Phase Iii ◽  
Clinical Activity ◽  
Open Label ◽  
Eligibility Criteria ◽  
Recist 1.1 ◽  
Platinum Based Chemotherapy ◽  
Patient Reported ◽  
Previously Treated

TPS9134 Background: Patients with mNSCLC who progress on anti–PD-L1/PD-1 therapy administered in combination with or after platinum-based chemotherapy (PBC) are mainly treated with docetaxel or pemetrexed monotherapy. These therapies only have modest clinical activity, leaving a high unmet medical need. Cabozantinib, a tyrosine kinase inhibitor (TKI), promotes an immune-permissive environment and may enhance the efficacy of PD-L1/PD-1 inhibitors, offering a promising second/third-line therapeutic opportunity for patients with mNSCLC. In a Phase Ib multi-cohort study (COSMIC-021; NCT03170960), cabozantinib plus atezolizumab (anti–PD-L1) showed an acceptable safety profile and promising efficacy (ORR: 27%; mDOR: 5.7 mo [range: 2.6-6.9]; disease control rate [CR + PR + SD]: 83%) in 30 patients with mNSCLC who had progressed after prior anti–PD-L1/PD-1 therapy plus chemotherapy (Neal et al. J Clin Oncol 2020). The Phase III CONTACT-01 study will further evaluate the efficacy and safety of atezolizumab plus cabozantinib versus docetaxel monotherapy in patients with mNSCLC who have progressed during or after prior treatment with anti–PD-L1/PD-1 therapy and PBC. Methods: CONTACT-01 (NCT04471428) is a Phase III, multi-center, randomized, open-label study that will enroll ≈350 patients from 150 to 200 sites internationally. Key eligibility criteria include histologically or cytologically confirmed mNSCLC, disease progression with concurrent or sequential anti–PD-L1/PD-1 treatment and PBC, measurable disease (RECIST 1.1), ECOG PS of 0-1 and the availability of tissue specimens for centralized PD-L1 testing or known PD-L1 status using a health authority–approved PD-L1 assay. Patients with NSCLC previously treated with cabozantinib, docetaxel or anti–PD-L1/PD-1 + VEGFR TKIs are excluded. Patients with known sensitizing EGFR/ALK mutations and active or untreated CNS metastases are also excluded. Patients will be randomized 1:1 to receive either atezolizumab (1200 mg IV every 3 weeks) + cabozantinib (40 mg orally once daily) or docetaxel (75 mg/m2 IV every 3 weeks). The primary endpoint is OS. Secondary endpoints include investigator-assessed PFS, ORR and DOR per RECIST 1.1; TTD in patient-reported physical function and global health status (EORTC QLQ-C30); investigator-assessed PFS rates at 6 months and 1 year; OS rates at 1 and 2 years; safety and PK. Clinical trial information: NCT04471428.

A phase II study of S-1 for previously treated small cell lung cancer (SCLC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19074-e19074
Author(s):  
K. Kudo ◽  
F. Ohyanagi ◽  
A. Horiike ◽  
E. Miyauchi ◽  
I. Motokawa ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Performance Status ◽  
Single Agent ◽  
Progression Free Survival ◽  
Median Number ◽  
Ecog Performance Status ◽  
Treatment Regimens ◽  
Platinum Based Chemotherapy ◽  
Previously Treated

e19074 Background: S-1 is a novel oral 5-fluorouracil derivative that exhibits obvious activity against various tumor types including NSCLC. However, the effects of S-1 against SCLC have not been reported. The present phase II trial assesses the efficacy and safety of S-1 in previously treated SCLC patients. Methods: Eligible patients had pathologically documented SCLC that relapsed after platinum-based chemotherapy, ECOG performance status (PS) 0–2, and adequate bone marrow, kidney and liver function. Patients with untreated or symptomatic brain metastasis were excluded. Treatment comprised the oral administration of S-1 at 40 mg/m2 twice each day for 28 days every 6 weeks. The primary end point was the objective tumor response rate (RECIST). Secondary endpoints included progression-free survival and overall survival. Results: Twenty-six evaluable patients were enrolled (Simon's two-stage optimal design; α = 0.1; β = 0.1; P0 = 0.05; P1 = 0.25) with the following characteristics: male: female, 22/4; median age, 68 (33 - 79) y; PS0–1, n = 21; PS2, n = 5. The median number of prior treatment regimens was 2 (1–3). S-1 was administered for a mean of 1.3 cycles (1 - 5). One patient (3.8%) partially responded, 10 (38.5%) had stable and 15 (57.7%) had progressive disease. The overall response rate was 3.8% and the disease control rate was 42.3%. The median time to progression was 33 days. The median survival time was 8.0 months and the 1-year survival rate was 23%. This regimen was well tolerated. The common grade 3/4 toxicities included neutropenia (7.7%), leukopenia (7.7%), anemia (7.7%), hyponatremia (7.7%), rush (7.7%), infection (7.7%), and diarrhea (3.8%). None of the patients developed febrile neutropenia and no deaths were attributed to treatment. Conclusions: S-1 is well tolerated but has low activity as a single agent in previously treated patients with SCLC. No significant financial relationships to disclose.

KEYNOTE-224: Phase II study of pembrolizumab in patients with previously treated advanced hepatocellular carcinoma.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. TPS504-TPS504 ◽  
Author(s):  
Andrew X. Zhu ◽  
Jennifer J. Knox ◽  
Masatoshi Kudo ◽  
Stephen L. Chan ◽  
Richard S. Finn ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Disease Progression ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Locoregional Therapy ◽  
Advanced Hepatocellular Carcinoma ◽  
Ecog Performance Status ◽  
Previously Treated

TPS504 Background: The tyrosine kinase inhibitor sorafenib is the standard of care for first-line hepatocellular carcinoma (HCC). For patients with HCC after disease progression on sorafenib or for those with intolerance to sorafenib, no approved therapies are available. Because HCC is often driven by inflammation and is also associated with a suppressed immunoenvironment, there is a strong rationale to evaluate immunotherapy in patients with this type of cancer. The single-arm, multisite, phase 2 KEYNOTE-224 study (ClinicalTrials.gov, NCT02702414) was designed to evaluate the efficacy and safety of the anti–PD-1 antibody pembrolizumab in patients with previously treated advanced HCC. Methods: Approximately 100 patients will be enrolled. Inclusion criteria include age ≥18 years, histologically or cytologically confirmed diagnosis of HCC Barcelona Clinic Liver Cancer (BCLC) stage C disease or BCLC stage B disease not amenable to or refractory to locoregional therapy, and disease not amenable to a curative treatment approach (eg, transplantation, surgery, or ablation). Patients must also have measurable disease based on RECIST v1.1 as confirmed by central imaging vendor review, documented objective radiographic progression after stopping treatment with sorafenib or intolerance to sorafenib, Child-Pugh liver score A, ECOG performance status 0-1, and predicted life expectancy > 3 months. Patients will be allocated to receive pembrolizumab 200 mg IV every 3 weeks for up to 35 cycles (~2 years) or until disease progression, unacceptable toxicity, patient withdrawal of consent, or investigator decision. Response will be assessed every 9 weeks per RECIST v1.1 by central imaging vendor review. Adverse events (AEs) will be assessed throughout treatment and for 30 days thereafter (90 days for serious AEs) and graded per NCI CTCAE v4.0. The primary end point is objective response rate per RECIST v1.1 by central imaging vendor review. Secondary end points are overall survival; safety and tolerability; and duration of response, disease control rate, time to progression, and progression-free survival per RECIST v1.1 by central imaging vendor review. Enrollment in KEYNOTE-224 is ongoing. Clinical trial information: NCT02702414.

Trastuzumab deruxtecan (T-DXd; DS-8201) in patients with HER2-mutated metastatic non-small cell lung cancer (NSCLC): Interim results of DESTINY-Lung01.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9504-9504 ◽  
Author(s):  
Egbert F. Smit ◽  
Kazuhiko Nakagawa ◽  
Misako Nagasaka ◽  
Enriqueta Felip ◽  
Yasushi Goto ◽  
...  
Keyword(s):  
Topoisomerase I ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Clinical Activity ◽  
Antibody Drug Conjugate ◽  
Ecog Performance Status ◽  
Platinum Based Chemotherapy ◽  
Grade 3

9504 Background: T-DXd is an antibody-drug conjugate composed of an anti-HER2 antibody, cleavable tetrapeptide-based linker, and topoisomerase I inhibitor payload. In a phase I trial, patients (pts) with HER2-mutated NSCLC who received T-DXd had a confirmed objective response rate (ORR) of 72.7% (8/11) (Tsurutani et al, WCLC 2018). DESTINY-Lung01 (NCT03505710) is an ongoing, multicenter, phase II study of T-DXd in pts with non-squamous NSCLC overexpressing HER2 or containing a HER2-activating mutation. We report data for the cohort with HER2 mutations after a median follow-up of 8.0 mo (range, 1.4-14.2 mo). Methods: Pts were treated with T-DXd 6.4 mg/kg every 3 weeks. The primary endpoint was confirmed ORR (complete response [CR] + partial response [PR]) by ICR. Additional endpoints were disease control rate (DCR; CR + PR + stable disease), duration of response (DOR), progression-free survival (PFS), and safety. Results: At data cutoff (25 Nov 2019), 42 pts (64.3% female) had received T-DXd. Median age was 63.0 years (range, 34-83 years; < 65 y, 59.5%); 45.2% had central nervous system metastases; ECOG performance status was 0 in 23.8% of pts and 1 in 76.2%. HER2 mutations were predominantly in the kinase domain (90.5%). Most pts (90.5%) had prior platinum-based chemotherapy and 54.8% had anti–PD-1 or –PD-L1 treatment; median number of prior treatment lines was 2 (range, 1-6). Median treatment duration was 7.75 mo (range, 0.7-14.3 mo); 45.2% of pts remained on treatment. Confirmed ORR by ICR among the 42 pts was 61.9% (95% CI, 45.6%-76.4%); median DOR was not reached at data cutoff; 16 of 26 responders remained on treatment at data cutoff; DCR was 90.5% (95% CI, 77.4%-97.3%); estimated median PFS was 14.0 mo (95% CI, 6.4-14.0 mo). All pts (42/42) had treatment-emergent adverse events (TEAEs); 64.3% were grade ≥ 3 (52.4% drug-related), including decreased neutrophil count (26.2%) and anemia (16.7%). There were 5 cases (11.9%) of drug-related interstitial lung disease (ILD) as adjudicated by an independent committee (all grade 2, no grade ≥ 3) and 1 case of grade 1 ILD is pending adjudication. TEAEs led to dose interruption in 25 pts (59.5%), dose reduction in 16 pts (38.1%), and treatment discontinuation in 10 pts (23.8%). Conclusions: T-DXd demonstrated promising clinical activity with high ORR and durable responses in pts with HER2-mutated NSCLC. The safety profile was generally consistent with previously reported studies. Clinical trial information: NCT03505710 .

Randomized phase II study of erlotinib alone and in combination with bortezomib in previously treated advanced non-small cell lung cancer (NSCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7680-7680 ◽  
Author(s):  
T. J. Lynch ◽  
D. W. Fenton ◽  
V. Hirsh ◽  
D. J. Bodkin ◽  
E. Middleman ◽  
...  
Keyword(s):  
Egf Receptor ◽  
Performance Status ◽  
Treatment Options ◽  
Sensory Neuropathy ◽  
Progression Free Survival ◽  
Clinical Activity ◽  
Ecog Performance Status ◽  
Combination Methods ◽  
Previously Treated ◽  
Grade 3

7680 Background: Treatment options for previously treated NSCLC are limited, warranting consideration of novel combinations. This study evaluated the activity and toxicity of erlotinib with bortezomib, a proteasome inhibitor. Dosing was based on the approved indication for erlotinib and on phase I data for the combination. Methods: Patients (pts) with Stage IIIB/IV NSCLC who progressed following one prior line of chemotherapy, with no prior exposure to an EGF-receptor inhibitor and ECOG performance status 0 or 1 were randomly assigned to erlotinib 150 mg po daily alone (arm A) or in combination with bortezomib 1.6 mg/m2 iv on days 1 and 8 (arm B) of a 21-day cycle. Response was evaluated by RECIST and toxicity was graded using NCI CTCAE 3.0. A Simon optimal two-stage design was used to evaluate anti-tumor activity in response-evaluable pts. Results: Fifty pts were treated at 17 sites (January-June 2006); baseline characteristics and treatment intensity were comparable in both arms. Among 24 response-evaluable pts in each arm, there were 3 partial responses (PR) and 1 complete response in arm A and 2 PR in arm B. Median progression-free survival (PFS) was 2.7 and 1.4 months in arms A and B, respectively. The study was halted as required at the planned interim analysis due to insufficient clinical activity in arm B. Activity and toxicity in arm A were consistent with published reports for erlotinib alone. Adverse-event profiles were as expected in both arms, with no significant additivity. In arm B, one pt died of pneumonia. The most common grade 3 treatment-related toxicity was skin rash (12% arm A and 8% arm B), and rash severity correlated with PFS: grades 2/3, 2.8 months PFS (20 pts); grades 0/1, 1.4 months PFS (28 pts), p=0.032. In arm B, one pt each had grade 3 anorexia, hypokalemia, and worsened peripheral sensory neuropathy compared with baseline. There were no grade 4 treatment related toxicities in either arm. Conclusions: The combination of erlotinib and bortezomib in the doses and schedules used in this trial was well tolerated but did not show sufficient activity at this dose and schedule to warrant further development. No significant financial relationships to disclose.

A phase II trial of gefitinib and pegylated interferon alfa 2b (PEG-IFN) in previously-treated renal cell carcinoma (RCC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16115-e16115
Author(s):  
D. W. Shek ◽  
J. Longmate ◽  
D. Quinn ◽  
K. Margolin ◽  
P. Twardowski ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Response Duration ◽  
Dose Schedule ◽  
Pegylated Interferon ◽  
Previously Treated ◽  
Ifn Treatment

e16115 Background: Modulation of the epidermal growth factor receptor (EGFR) pathway is relevant to IFN activity in RCC. Cell lines sensitive to IFN's antiproliferative effects downregulate EGFR, while IFN treatment of resistant cells precludes such an effect. (Eisenkraft et al, Cancer Res. 1991) Lack of EGFR down-regulation may thus be responsible in part for IFN resistance. To explore this hypothesis, we conducted a trial of the EGFR tyrosine kinase inhibitor gefitinib plus PEG-IFN in RCC patients (pts). Methods: Unresectable or metastatic RCC pts (no limit on prior therapies; performance status 0–2, and adequate end-organ function) were eligible. Prior IFN was allowed. Dose schedule: PEG-IFN SQ weekly (6μg/kg/week or 4 μg/kg/week) × 12 weeks and gefitinib 250 mg po daily until progression. A 6-month progression free survival (PFS) rate of 50% was considered promising (vs. 30%) in a two-stage design incorporating the Green-Dahlberg rule. We accrued 21 patients in the first-stage of accrual. Results: Pt characteristics: Males -16; median age - 56 years; Prior nephrectomy - 12. All had > 1 prior systemic therapy . Accrual slowed with increased use of small molecule kinase inhibitors, bevacizumab, and temsirolimus for RCC. At 6 months, PFS was 26% (95% CI: 9%, 49%); 20% (4 pts) had died. Best responses by RECIST: complete (1), partial (4), stable (8); progression (4). Response duration: CR (35+ months) and PR (3, 5, 5, 38+ months). Median time to treatment failure was 18.4 weeks (95%CI: 7.4, 24.9). Median PFS and overall survival were 23 and 53 weeks, respectively. Most common treatment-related toxicities were leucopenia, thrombocytopenia, rash, nausea, diarrhea, and hyperglycemia. Conclusions: Although gefitinib plus PEG-IFN did not meet the pre-specified 6-month PFS of 50%, it appears to have activity similar to other first-line therapies even in this previously-treated setting. (Supported by Astra Zeneca) [Table: see text]

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