Dosage modifications, including dosage interruption, reduction, or discontinuation, due to intolerable toxicities are frequently required during oncology clinical trials. The impact of dosage modifications on clinical efficacy has not been well characterized. As the first step to address this issue, we conducted a landscape analysis of new molecular entities (NMEs) of oncology small molecule drugs and antibody-drug conjugates (ADCs) approved by FDA between 2016 and 2021 to characterize the prevalence of dosage modifications in pivotal trials. Data on dosage modifications, incidence of adverse reactions (ARs), pharmacokinetic (PK) parameters, and rationale of the recommended dosing regimens for the NMEs was collected from the United States Prescribing Information (USPI), clinical pharmacology and clinical summaries and reviews, as well as clinical study reports (CSRs) and Investigator’s Brochures. The rate (%) of dosage reductions, interruptions, discontinuations, and the incidence of ARs associated with the toxicities leading to dosage modifications were evaluated. In general, the NMEs with the most prevalent dosage interruptions are cyclin-dependent kinase (CDK) 4/6 inhibitors, the tumor suppressor protein (TSP) inhibitor (selinexor), phosphoinositide 3-kinase (PI3K) inhibitors, as well as fibroblast growth factor receptor (FGFR) and poly ADP ribose polymerase (PARP) inhibitors (Table 1). PARP inhibitors had the greatest incidence of dosage reductions (%) followed by inhibitors of CDK 4/6 and selinexor. Regarding treatment discontinuations, the hedgehog pathway inhibitor, glasdegib, had the highest rate of discontinuations followed by selinexor and mesenchymal-epithelial transition (MET) inhibitors (Table 1). Overall, the NMEs with the maximum tolerated dose (MTD) as the recommended dosing regimen (26%) were associated with a higher likelihood of dosage reductions compared to those with recommended dosing regimens that were lower than the MTD (36% vs. 23%). In general, the number of recommended dose reductions did not exceed three levels, and the magnitude of dose reduction was 32%, 51%, and 63% for the 1st, 2nd, and 3rd reduced dose levels, respectively, from the recommended starting dose. Post marketing requirements (PMRs) were issued for select NMEs (12%) to address dosage optimization pertinent to tolerability. The time to dosage reductions and differences in the observed rate of dosage modifications across the lines of treatment was not consistently reported with an overall deficiency in collection of PK samples that coincide with the occurrence of these events. Although dosage reductions and interruptions are common, the impact of dosage modifications on the clinical outcome was evaluated in only 16% (n=8) of the NME submissions approved in the past 5 years. Further assessment of the impact of dosage reduction and interruptions on clinical efficacy is warranted. Table 1. Description of The Rate of Dosage Reductions, Interruptions, and Discontinuations in Patients Who Received the Recommended Dosing Regimen for Each New Molecular Entity Class approved between 2016-2021 New Molecular Entity Class Dose Reductions Dose Interruptions Dose Discontinuations n % ± SD n % ± SD n % ± SD ADCs 7 20 ± 12 7 47 ± 1 7 15 ± 10 CDK 4 and 6 Inhibitors 4 43 ± 5 1 77 4 8 ± 1 FGFR Inhibitors 2 34 ± 28 2 56 ± 18 2 11 ± 3 PARP Inhibitors 3 50 ± 21 3 54 ± 12 3 10 ± 5 PI3K Inhibitors 4 28 ± 19 4 62 ± 13 4 17 ± 13 Androgen Receptor Inhibitors 2 19 ± 19 2 23 ± 14 2 10 ± 1 EGFR and HER2 Inhibitors 3 39 ± 24 3 57 ± 4 3 17 ± 11 MEK Inhibitors 3 19 ± 5 3 48 ± 28 3 7 ± 4 BTK Inhibitors 2 5 ± 2 2 31 ± 4 2 5 ± 4 IDH Enzyme Inhibitors 2 4 ± 1 2 41 ± 4 2 15 ± 3 FLT Inhibitors 3 36 ± 21 3 44 ± 10 3 11 ± 2 TRKA, B, and C Inhibitors 3 29 ± 7 3 44 ± 6 3 10 ± 3 PDGFR, VEGFR, and RET Inhibitors 5 29 ± 16 5 46 ± 14 5 13 ± 6 MET Inhibitors 2 27 ± 5 2 49 ± 7 2 18 ± 3 Tumor Suppressor Protein Inhibitor 1 43 1 69 1 27 Alkylating Drugs 2 26 ± 1 2 46 ± 22 2 12 ± 14 Hedgehog Pathway Inhibitor 1 26 1 not reported 1 36