Non–Small-Cell Lung Cancer: Dose Escalation by Target Splitting with Asymmetric Collimation

2001 ◽  
Vol 3 (2) ◽  
pp. 151-153 ◽  
Author(s):  
Karl Wurstbauer ◽  
Heinz Deutschmann ◽  
Felix Sedlmayer ◽  
H. Dieter Kogelnik
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Dose Escalation ◽  
Small Cell ◽  
Small Cell Lung ◽  
Target Splitting

A first-in-human study of mirzotamab clezutoclax as monotherapy and in combination with taxane therapy in relapsed/refractory solid tumors: Dose escalation results.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3015-3015
Author(s):  
Anthony W. Tolcher ◽  
Benedito A. Carneiro ◽  
Afshin Dowlati ◽  
Albiruni Ryan Abdul Razak ◽  
Young Kwang Chae ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Solid Tumors ◽  
Cell Lung Cancer ◽  
Dose Escalation ◽  
Lymphocyte Count ◽  
B Cell Lymphoma ◽  
Small Cell ◽  
Small Cell Lung ◽  
Grade 3

3015 Background: Mirzotamab clezutoclax (ABBV-155) is a first-in-class antibody drug conjugate comprised of a BCL-XL (B-cell lymphoma - extra long) inhibitor, solubilizing linker, and a monoclonal anti-B7H3 antibody. Methods: Patients (pts) with relapsed and/or refractory (R/R) solid tumors were administered mirzotamab clezutoclax with or without paclitaxel. Dose escalation of mirzotamab clezutoclax was guided by Bayesian continual reassessment. Primary outcomes were to determine the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D). Secondary outcomes: safety, pharmacokinetics, and overall response rate per RECIST v1.1. Results: As of November 6, 2020, 31 pts received mirzotamab clezutoclax monotherapy (monoTx) and 28 pts received combination therapy with paclitaxel (comboTx). Overall demographics: median age 62 years (range 25–79); 61% female; 86% white; 24% ECOG 0, 76% ECOG 1; 51% had > 3 prior systemic therapies. The median duration of mirzotamab clezutoclax exposure was 3 cycles (range 1–14) for monoTx and 5 cycles (range 1–14) for comboTx. There were no dose limiting toxicities (DLT) reported with monoTx. In comboTx, 2 pts experienced a DLT: Grade 4 neutrophil count decreased and Grade 3 lymphocyte count decreased considered related to paclitaxel. 97% of all pts had adverse events (AEs). The most common AEs (in ≥20% of pts) overall were fatigue (39%), nausea (25%), diarrhea and arthralgia (22% each), vomiting and hypokalemia (20% each). AEs in ≥5 pts related to mirzotamab cleuzutoclax were fatigue (27%), diarrhea (12%), and nausea (9%). Related Grade 3/4 AEs overall (in > 1 patient) included anemia, lymphocyte count decreased, fatigue, and diarrhea (3% each). One patient on monoTx experienced a fatal cardiac arrest. No fatal AEs occurred on comboTx. Responses were observed with comboTx as shown in the Table. Conclusions: Mirzotamab clezutoclax as monotherapy and with paclitaxel demonstrates a tolerable safety profile (MTD not reached) with anti-tumor activity in R/R solid tumors. Further investigation in prospectively-selected B7H3 positive tumors as monoTx in pts with R/R small cell lung cancer and with paclitaxel in pts with R/R breast cancer and docetaxel in pts with R/R non-small cell lung cancer in the dose expansion phase is ongoing. Clinical trial information: NCT03595059. [Table: see text]

PO-1844 Adaptive dose escalation for non-small cell lung cancer patients treated with VMAT

2021 ◽  
Vol 161 ◽  
pp. S1572-S1573
Author(s):  
N.S. Tambe ◽  
I.M. Pires ◽  
C. Moore ◽  
A. Wieczorek ◽  
S. Upadhyay ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Patients ◽  
Cell Lung Cancer ◽  
Dose Escalation ◽  
Small Cell ◽  
Small Cell Lung ◽  
Lung Cancer Patients

scholarly journals Dose escalation of osimertinib for intracranial progression in EGFR mutated non-small-cell lung cancer with brain metastases

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Iris M Goldstein ◽  
Laila C Roisman ◽  
Shoshana Keren-Rosenberg ◽  
Julia Dudnik ◽  
Hovav Nechushtan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Dose Escalation ◽  
Resistance Mutation ◽  
Small Cell ◽  
Second Line ◽  
Small Cell Lung ◽  
Line Setting ◽  
Egfr Mutated

Abstract Background Osimertinib is a selective irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) with increased penetration across the blood–brain barrier compared with previous EGFR-TKIs, and thus, a 52% reduction in the risk of intracranial disease progression is seen when it is used as a first line of therapy compared with gefitinib and erlotinib. It is also efficient as second-line therapy for patients who developed the T790M resistance mutation following treatment with previous generation TKIs. Here, we report 11 patients who were treated by an increasing dose of osimertinib from 80 mg to 160 mg QD orally following intracranial progression in either first- or second-line setting. Methods This is a subcohort analysis from a larger nonrandomized, phase 2, open-label trial, evaluating the efficacy of osimertinib dose escalation from 80 mg to 160 mg in EGFR-mutated advanced non-small-cell lung cancer (NSCLC) patients with intracranial progression in either first- (arm A) or second-line setting (arm B for T790M+ and C for T790M−). Results Eleven patients, 5 in arm A, 4 in arm B, and 2 in arm C were reported in this study. The mPFS of osimertinib before dose escalation was 11.4 ± 8.9 (6.6–30.7) months for arm A, 8.7 ± 1.8 (6.3–11.2) for arm B, and 14.5 ± 7.8 (6.7–22.3) for arm C. Intracranial response rate to dose escalation was 54% (6 of 11) with 2 of 11 having intracranial stability. Median iPFS was 4.3 ± 7.4 (0.7–25.5) months; 3.8 ± 6.4 (1.8–18.9), 5.6 ± 9.7 (0.7–25.5), and 7.0 ± 2.7 (4.3–9.6) for arms A/B/C, respectively. Dose escalation was well tolerated with diarrhea and paronychia as the main dose-limiting symptoms. Conclusions Osimertinib 160 mg is feasible and may offer a therapeutic alternative for patients with isolated intracranial progression on osimertinib standard (80 mg) dose. Further studies on CNS osimertinib pharmacokinetics are needed to test this hypothesis.

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