Dataset Information

Tumor Dynamic Model-Based Decision Support for Phase Ib/II Combination Studies: A Retrospective Assessment Based on Resampling of the Phase III Study IMpower150.

ABSTRACT:

Purpose

Model-based tumor growth inhibition (TGI) metrics are increasingly incorporated into go/no-go decisions in early clinical studies. To apply this methodology to new investigational combinations requires independent evaluation of TGI metrics in recently completed Phase III trials of effective immunotherapy.

Patients and methods

Data were extracted from IMpower150, a positive, randomized, Phase III study of first-line therapy in 1,202 patients with non-small cell lung cancer. We resampled baseline characteristics and longitudinal sum of longest diameters of tumor lesions of patients from both arms, atezolizumab+ bevacizumab+chemotherapy (ABCP) versus BCP, to mimic Phase Ib/II studies of 15 to 40 patients/arm with 6 to 24 weeks follow-up. TGI metrics were estimated using a bi-exponential TGI model. Effect sizes were calculated as TGI metrics geometric mean ratio (GMR), objective response rate (ORR) difference (d), and progression-free survival (PFS), hazard ratio (HR) between arms. Correct and incorrect go decisions were evaluated as the probability to achieve desired effect sizes in ABCP versus BCP and BCP versus BCP, respectively, across 500 replicated subsamples for each design.

Results

For 40 patients/24 weeks follow-up, correct go decisions based on probability tumor growth rate (KG) GMR <0.90, dORR >0.10, and PFS HR <0.70 were 83%, 69%, and 58% with incorrect go decision rates of 4%, 12%, and 11%, respectively. For other designs, the ranking did not change with TGI metrics consistently overperforming RECIST endpoints. The predicted overall survival (OS) HR was around 0.80 in most of the scenarios investigated.

Conclusions

Model-based estimate of KG GMR is an exploratory endpoint that informs early clinical decisions for combination studies.

SUBMITTER: Bruno R

PROVIDER: S-EPMC10023325 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Publications

Tumor Dynamic Model-Based Decision Support for Phase Ib/II Combination Studies: A Retrospective Assessment Based on Resampling of the Phase III Study IMpower150.

Bruno René R Marchand Mathilde M Yoshida Kenta K Chan Phyllis P Li Haocheng H Zou Wei W Mercier Francois F Chanu Pascal P Wu Benjamin B Lee Anthony A Li Chunze C Jin Jin Y JY Maitland Michael L ML Reck Martin M Socinski Mark A MA

Clinical cancer research : an official journal of the American Association for Cancer Research 20230301 6

<h4>Purpose</h4>Model-based tumor growth inhibition (TGI) metrics are increasingly incorporated into go/no-go decisions in early clinical studies. To apply this methodology to new investigational combinations requires independent evaluation of TGI metrics in recently completed Phase III trials of effective immunotherapy.<h4>Patients and methods</h4>Data were extracted from IMpower150, a positive, randomized, Phase III study of first-line therapy in 1,202 patients with non-small cell lung cancer. ...[more]

PMID: 36595566

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Dataset Information

Tumor Dynamic Model-Based Decision Support for Phase Ib/II Combination Studies: A Retrospective Assessment Based on Resampling of the Phase III Study IMpower150.

Purpose

Patients and methods

Results

Conclusions

Publications

Tumor Dynamic Model-Based Decision Support for Phase Ib/II Combination Studies: A Retrospective Assessment Based on Resampling of the Phase III Study IMpower150.

Similar Datasets

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