Results of a Randomized, Double-Blind, Placebo-Controlled, Phase 1b/2 Trial of Nabpaclitaxel + Gemcitabine ± Olaratumab in Treatment-Naïve Participants with Metastatic Pancreatic Cancer
The efficacy and safety of olaratumab plus nabpaclitaxel and gemcitabine in treatment-naïve participants with metastatic pancreatic ductal adenocarcinoma was evaluated. An initial phase 1b dose-escalation trial was conducted to determine the olaratumab dose for the phase 2 trial, a randomized, doubl...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-03-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/16/7/1323 |
| _version_ | 1797212864892633088 |
|---|---|
| author | Faithlore P. Gardner Zev A. Wainberg Christos Fountzilas Nathan Bahary Mark S. Womack Teresa Macarulla Ignacio Garrido-Laguna Patrick M. Peterson Erkut Borazanci Melissa Johnson Matteo Ceccarelli Uwe Pelzer |
| author_facet | Faithlore P. Gardner Zev A. Wainberg Christos Fountzilas Nathan Bahary Mark S. Womack Teresa Macarulla Ignacio Garrido-Laguna Patrick M. Peterson Erkut Borazanci Melissa Johnson Matteo Ceccarelli Uwe Pelzer |
| author_sort | Faithlore P. Gardner |
| collection | DOAJ |
| description | The efficacy and safety of olaratumab plus nabpaclitaxel and gemcitabine in treatment-naïve participants with metastatic pancreatic ductal adenocarcinoma was evaluated. An initial phase 1b dose-escalation trial was conducted to determine the olaratumab dose for the phase 2 trial, a randomized, double-blind, placebo-controlled trial to compare overall survival (OS) in the olaratumab arm vs. placebo arms. In phase 1b, 22 participants received olaratumab at doses of 15 and 20 mg/kg with a fixed dose of nabpaclitaxel and gemcitabine. In phase 2, 159 participants were randomized to receive olaratumab 20 mg/kg in cycle 1 followed by 15 mg/kg in the subsequent cycles (n = 81) or the placebo (n = 78) on days 1, 8, and 15 of a 28-day cycle, plus nabpaclitaxel and gemcitabine. The primary objective of the trial was not met, with a median OS of 9.1 vs. 10.8 months (hazard ratio [HR] = 1.05; 95% confidence interval [CI]: 0.728, 1.527; <i>p</i> = 0.79) and the median progression-free survival (PFS) was 5.5 vs. 6.4 months (HR = 1.19; 95% CI: 0.806, 1.764; <i>p</i> = 0.38), in the olaratumab vs. placebo arms, respectively. The most common treatment-emergent adverse event of any grade across both arms was fatigue. Olaratumab plus chemotherapy failed to improve the OS or PFS in participants with metastatic PDAC. There were no new safety signals. |
| first_indexed | 2024-04-24T10:49:10Z |
| format | Article |
| id | doaj.art-a853f4e8e50e44b0a0a9e297a6693aed |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-04-24T10:49:10Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-a853f4e8e50e44b0a0a9e297a6693aed2024-04-12T13:16:02ZengMDPI AGCancers2072-66942024-03-01167132310.3390/cancers16071323Results of a Randomized, Double-Blind, Placebo-Controlled, Phase 1b/2 Trial of Nabpaclitaxel + Gemcitabine ± Olaratumab in Treatment-Naïve Participants with Metastatic Pancreatic CancerFaithlore P. Gardner0Zev A. Wainberg1Christos Fountzilas2Nathan Bahary3Mark S. Womack4Teresa Macarulla5Ignacio Garrido-Laguna6Patrick M. Peterson7Erkut Borazanci8Melissa Johnson9Matteo Ceccarelli10Uwe Pelzer11Florida Cancer Specialists and Research Institute, Cape Coral, FL 34471, USAUCLA School of Medicine, Los Angeles, CA 90095, USARoswell Park Comprehensive Cancer Center, Buffalo, NY 14203, USAAllegheny Health Network Cancer Institute, Pittsburgh, PA 15212, USATennessee Oncology, Chattanooga, TN 37129, USAHospital Vall d’Hebrón, Vall d’Hebrón Institute of Oncology (VHIO), 08035 Barcelona, SpainDepartment of Internal Medicine, Huntsman Cancer Institute at University of Utah, Salt Lake City, UT 84112, USAEli Lilly & Company, Indianapolis, IN 46285, USAHonorHealth Research Institute, Scottsdale, AZ 85258, USATennessee Oncology, Nashville, TN 37203, USAEli Lilly & Company, Sesto Fiorentino, 50019 Florence, ItalyMedical Department, Division of Hematology, Oncology and Tumorimmunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Charitéplatz 1, 10117 Berlin, GermanyThe efficacy and safety of olaratumab plus nabpaclitaxel and gemcitabine in treatment-naïve participants with metastatic pancreatic ductal adenocarcinoma was evaluated. An initial phase 1b dose-escalation trial was conducted to determine the olaratumab dose for the phase 2 trial, a randomized, double-blind, placebo-controlled trial to compare overall survival (OS) in the olaratumab arm vs. placebo arms. In phase 1b, 22 participants received olaratumab at doses of 15 and 20 mg/kg with a fixed dose of nabpaclitaxel and gemcitabine. In phase 2, 159 participants were randomized to receive olaratumab 20 mg/kg in cycle 1 followed by 15 mg/kg in the subsequent cycles (n = 81) or the placebo (n = 78) on days 1, 8, and 15 of a 28-day cycle, plus nabpaclitaxel and gemcitabine. The primary objective of the trial was not met, with a median OS of 9.1 vs. 10.8 months (hazard ratio [HR] = 1.05; 95% confidence interval [CI]: 0.728, 1.527; <i>p</i> = 0.79) and the median progression-free survival (PFS) was 5.5 vs. 6.4 months (HR = 1.19; 95% CI: 0.806, 1.764; <i>p</i> = 0.38), in the olaratumab vs. placebo arms, respectively. The most common treatment-emergent adverse event of any grade across both arms was fatigue. Olaratumab plus chemotherapy failed to improve the OS or PFS in participants with metastatic PDAC. There were no new safety signals.https://www.mdpi.com/2072-6694/16/7/1323olaratumabgemcitabinenabpaclitaxelmetastatic pancreatic cancer |
| spellingShingle | Faithlore P. Gardner Zev A. Wainberg Christos Fountzilas Nathan Bahary Mark S. Womack Teresa Macarulla Ignacio Garrido-Laguna Patrick M. Peterson Erkut Borazanci Melissa Johnson Matteo Ceccarelli Uwe Pelzer Results of a Randomized, Double-Blind, Placebo-Controlled, Phase 1b/2 Trial of Nabpaclitaxel + Gemcitabine ± Olaratumab in Treatment-Naïve Participants with Metastatic Pancreatic Cancer Cancers olaratumab gemcitabine nabpaclitaxel metastatic pancreatic cancer |
| title | Results of a Randomized, Double-Blind, Placebo-Controlled, Phase 1b/2 Trial of Nabpaclitaxel + Gemcitabine ± Olaratumab in Treatment-Naïve Participants with Metastatic Pancreatic Cancer |
| title_full | Results of a Randomized, Double-Blind, Placebo-Controlled, Phase 1b/2 Trial of Nabpaclitaxel + Gemcitabine ± Olaratumab in Treatment-Naïve Participants with Metastatic Pancreatic Cancer |
| title_fullStr | Results of a Randomized, Double-Blind, Placebo-Controlled, Phase 1b/2 Trial of Nabpaclitaxel + Gemcitabine ± Olaratumab in Treatment-Naïve Participants with Metastatic Pancreatic Cancer |
| title_full_unstemmed | Results of a Randomized, Double-Blind, Placebo-Controlled, Phase 1b/2 Trial of Nabpaclitaxel + Gemcitabine ± Olaratumab in Treatment-Naïve Participants with Metastatic Pancreatic Cancer |
| title_short | Results of a Randomized, Double-Blind, Placebo-Controlled, Phase 1b/2 Trial of Nabpaclitaxel + Gemcitabine ± Olaratumab in Treatment-Naïve Participants with Metastatic Pancreatic Cancer |
| title_sort | results of a randomized double blind placebo controlled phase 1b 2 trial of nabpaclitaxel gemcitabine olaratumab in treatment naive participants with metastatic pancreatic cancer |
| topic | olaratumab gemcitabine nabpaclitaxel metastatic pancreatic cancer |
| url | https://www.mdpi.com/2072-6694/16/7/1323 |
| work_keys_str_mv | AT faithlorepgardner resultsofarandomizeddoubleblindplacebocontrolledphase1b2trialofnabpaclitaxelgemcitabineolaratumabintreatmentnaiveparticipantswithmetastaticpancreaticcancer AT zevawainberg resultsofarandomizeddoubleblindplacebocontrolledphase1b2trialofnabpaclitaxelgemcitabineolaratumabintreatmentnaiveparticipantswithmetastaticpancreaticcancer AT christosfountzilas resultsofarandomizeddoubleblindplacebocontrolledphase1b2trialofnabpaclitaxelgemcitabineolaratumabintreatmentnaiveparticipantswithmetastaticpancreaticcancer AT nathanbahary resultsofarandomizeddoubleblindplacebocontrolledphase1b2trialofnabpaclitaxelgemcitabineolaratumabintreatmentnaiveparticipantswithmetastaticpancreaticcancer AT markswomack resultsofarandomizeddoubleblindplacebocontrolledphase1b2trialofnabpaclitaxelgemcitabineolaratumabintreatmentnaiveparticipantswithmetastaticpancreaticcancer AT teresamacarulla resultsofarandomizeddoubleblindplacebocontrolledphase1b2trialofnabpaclitaxelgemcitabineolaratumabintreatmentnaiveparticipantswithmetastaticpancreaticcancer AT ignaciogarridolaguna resultsofarandomizeddoubleblindplacebocontrolledphase1b2trialofnabpaclitaxelgemcitabineolaratumabintreatmentnaiveparticipantswithmetastaticpancreaticcancer AT patrickmpeterson resultsofarandomizeddoubleblindplacebocontrolledphase1b2trialofnabpaclitaxelgemcitabineolaratumabintreatmentnaiveparticipantswithmetastaticpancreaticcancer AT erkutborazanci resultsofarandomizeddoubleblindplacebocontrolledphase1b2trialofnabpaclitaxelgemcitabineolaratumabintreatmentnaiveparticipantswithmetastaticpancreaticcancer AT melissajohnson resultsofarandomizeddoubleblindplacebocontrolledphase1b2trialofnabpaclitaxelgemcitabineolaratumabintreatmentnaiveparticipantswithmetastaticpancreaticcancer AT matteoceccarelli resultsofarandomizeddoubleblindplacebocontrolledphase1b2trialofnabpaclitaxelgemcitabineolaratumabintreatmentnaiveparticipantswithmetastaticpancreaticcancer AT uwepelzer resultsofarandomizeddoubleblindplacebocontrolledphase1b2trialofnabpaclitaxelgemcitabineolaratumabintreatmentnaiveparticipantswithmetastaticpancreaticcancer |