Citations 2
Treatment Effect Reanalysis of the Randomized Individual Screening Trial of Innovative Glioblastoma Therapy in Newly Diagnosed Glioblastoma With External Control Data
Gupta, Tulika Rudra, Polley, Mei‐Yin C. , Redd, Robert , Lee, Eudocia Q., Arrillaga‐Romany, Isabel , Tan, Yujue, Welch, Mary R., Galanis, E, Ahluwalia, Manmeet S., Colman, Howard , Nabors, L. Burt, Hepel, Jaroslaw, Elinzano, Heinrich, Chukwueke, Ugonma N., Beroukhim, Rameen, Nayak, L., McFaline-Figueroa, J. Ricardo, Batchelor, Tracy T. , Lu‐Emerson, Christine , Bi, W. L., Arnaout, Omar, Peruzzi, Pier Paolo, Haas-Kogan, Daphne, Aizer, Ayal , Doherty, Lisa, Chiocca, E Antonio, Reardon, David A. , Wen, Patrick Y. , Trippa, Lorenzo , Rahman, Rifaquat, Gilbert, Mark R. , Redd, Robert , Lee, Eudocia Q , Gilbert, Mark R , Touat, Mehdi , Welch, Mary R , Ahluwalia, Manmeet S , Colman, Howard , Nabors, Louis Burt , Schiff, David , Nayak, Lakshmi , Batchelor, Tracy T , Kaley, Thomas , Lu-Emerson, Christine , Mellinghoff, Ingo K , Peruzzi, Pier Paolo , Haas-Kogan, Daphne , Tanguturi, Shyam K , Aizer, Ayal , Chiocca, E Antonio , Reardon, David A , Ligon, Keith L , Weller, Michael , Mehta, Minesh P , Wen, Patrick Yung , Rahman, Rifaquat , Lee, Eudocia Q. , Arrillaga‐Romany, Isabel , Drappatz, Jan , Galanis, Evanthia , Ahluwalia, Manmeet S. , Nabors, Burt , Hepel, Jaroslaw T., Elinzano, Heinrich, Chukwueke, Ugonma , Nayak, Lakshmi , McFaline-Figueroa, J Ricardo , Mellinghoff, Ingo K. , Arnaout, Omar M. , Haas‐Kogan, Daphne A. , Doherty, Lisa, Santagata, Sandro , Meredith, David M. , Mehta, Minesh P. , Rahman, Rifaquat
Journal of Clinical Oncology | May 22, 2026 | Volume: 44 | Issue: 21 | Pages: 2048-2058
PURPOSE Integrating external control data into clinical trial designs and analyses has the potential to accelerate drug development processes. We reanalyzed the three experimental arms of the Individual Screening Trial of Innovative Glioblastoma Therapy (INSIGhT), a randomized phase II platform trial in newly diagnosed O 6 -methylguanine-DNA methyltransferase-unmethylated glioblastoma (ClinicalTrials.gov identifier: NCT02977780 ). To evaluate the validity of using external data sets, we compared treatment effect estimates based on internal INSIGhT control data and matched external control data. METHODS The three experimental arms of INSIGhT (abemaciclib [n = 72], neratinib [n = 80], and CC-115 [n = 12]) did not improve survival compared with internal controls (standard chemoradiation [n = 70]). We derived external control patient-level data from multiple real-world and clinical trial data sets. We applied propensity score matching and Cox proportional hazards models to estimate treatment effects with external controls. Additionally, using this glioblastoma (GBM) data collection, we specified simulation scenarios to evaluate trial designs that integrate external controls. RESULTS After matching to external controls, no survival benefit was observed for patients receiving abemaciclib (hazard ratio [HR], 1.00 [95% CI, 0.75 to 1.34]), neratinib (HR, 0.93 [95% CI, 0.70 to 1.24]), or CC-115 (HR, 0.88 [95% CI, 0.41 to 1.88]). Simulations, together with the INSIGhT data and a collection of GBM data sets, allowed us to examine efficiencies and risks of clinical trial designs that leverage external control data. CONCLUSION The use of carefully matched external controls, to replace or augment the internal controls of INSIGhT, produced treatment effect estimates that were similar to previously published analyses. Single-arm trial designs and hybrid randomized designs incorporating propensity score–matched external control data evaluated treatment effects in the early-phase testing of experimental therapies in newly diagnosed GBM. The validity of this approach and risks of bias depended on the availability of comprehensive and accurate data on all potential confounders, in the absence of unmeasured confounding.
Autologous stem cell transplantation after anti-PD-1 therapy for multiply relapsed or refractory Hodgkin lymphoma
Redd, Robert , Nishihori, Taiga , Nieto, Yago , Darrah, Justin , Rao, Uttam K. , Byrne, Michael , Bond, David A. , Maddocks, Kami J. , Spinner, Michael A. , Advani, Ranjana H. , Ballard, Hatcher J. , Svoboda, Jakub , Singh, Anurag K. , Modi, Dipenkumar , Ramchandren, Radhakrishnan , Cohen, Jonathon B. , Frigault, Matthew J. , Chen, Yi‐Bin , Serritella, Anthony V. , Kline, J., Ansell, Stephen M. , Nathan, Sunita , Rahimian, Maryam, Shah, Mansi , David, Kevin A. , Park, Steven , Beaven, Anne , Habib, Alma , Bachanová, Veronika , Nakhoda, Shazia , Lynch, Ryan C. , Smith, Stephen D. , Ho, Vincent T. , LaCasce, Ann S. , Armand, Philippe , Herrera, Alex F. , Redd, Robert , Bachanova, Veronika , Nishihori, Taiga , Nieto, Yago , Advani, Ranjana H , Park, Steven I , Bond, David A , Merryman, Reid W. , Chavez, Julio C , McGuirk, Joseph P. , Romancik, Jason T. , Joyce, Robin , Khan, Nadia
Blood Advances | March 12, 2021 | Volume: 5 | Issue: 6 | Pages: 1648-1659
10.1182/bloodadvances.2020003556
Abstract Autologous stem cell transplantation (ASCT) can be curative for patients with relapsed/refractory Hodgkin lymphoma (HL). Based on studies suggesting that anti-PD-1 monoclonal antibodies (mAbs) can sensitize patients to subsequent chemotherapy, we hypothesized that anti-PD-1 therapy before ASCT would result in acceptable outcomes among high-risk patients who progressed on or responded insufficiently to ≥1 salvage regimen, including chemorefractory patients who are traditionally considered poor ASCT candidates. We retrospectively identified 78 HL patients who underwent ASCT after receiving an anti-PD-1 mAb (alone or in combination) as third-line or later therapy across 22 centers. Chemorefractory disease was common, including 42 patients (54%) refractory to ≥2 consecutive systemic therapies immediately before anti-PD-1 treatment. Fifty-eight (74%) patients underwent ASCT after anti-PD-1 treatment, while 20 patients (26%) received additional therapy after PD-1 blockade and before ASCT. Patients received a median of 4 systemic therapies (range, 3-7) before ASCT, and 31 patients (41%) had a positive pre-ASCT positron emission tomography (PET) result. After a median post-ASCT follow-up of 19.6 months, the 18-month progression-free survival (PFS) and overall survival were 81% (95% CI, 69-89) and 96% (95% confidence interval [CI], 87-99), respectively. Favorable outcomes were observed for patients who were refractory to 2 consecutive therapies immediately before PD-1 blockade (18-month PFS, 78%), had a positive pre-ASCT PET (18-month PFS, 75%), or received ≥4 systemic therapies before ASCT (18-month PFS, 73%), while PD-1 nonresponders had inferior outcomes (18-month PFS, 51%). In this high-risk cohort, ASCT after anti-PD-1 therapy was associated with excellent outcomes, even among heavily pretreated, previously chemorefractory patients.