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Clinical Trial
. 2025 Oct 1;30(10):oyaf284.
doi: 10.1093/oncolo/oyaf284.

Phase I study of palbociclib with cisplatin or carboplatin in the management of patients with advanced pancreatic cancer

Olatunji B Alese  1   2 , Robert Donald Harvey  1   2 , Christina Wu  3 , Elise Hitron  2 , Hannah Collins  2 , Suzanne Scott  2 , Conor Steuer  1   2 , Mehmet A Bilen  1   2 , Bradley C Carthon  1   2 , Jeffrey M Switchenko  4 , Suresh S Ramalingam  1   2 , Taofeek K Owonikoko  5
Affiliations
Clinical Trial

Phase I study of palbociclib with cisplatin or carboplatin in the management of patients with advanced pancreatic cancer

Olatunji B Alese et al. Oncologist. .

Abstract

Importance: The addition of agents targeting critical signal mediators of cancer cell proliferation such as cyclin-dependent kinases (CDK) potentiates the efficacy of platinum chemotherapy.ObjectiveTo determine the safety and efficacy of palbociclib combined with cisplatin (cis) or carboplatin (carbo) in advanced solid malignanciesDesignEnrollment on dose escalation (part I) proceeded using the Bayesian adaptive design Escalation with Overdose Control (EWOC).SettingSingle institution investigator initiated trial.

Participants: Patients with any advanced cancer after at least one prior therapy were enrolled on dose escalation to determine recommended phase II doses (RP2D). Expansion cohorts were then opened for pancreaticobiliary tract cancers.InterventionEscalating doses of palbociclib in combination with different doses of cisplatin or carboplatin.Main Outcomes and MeasuresPrimary endpoint was objective response rate (ORR). Secondary endpoints included safety, overall survival (OS), and progression-free survival (PFS).

Results: We enrolled 39 patients on dose escalation (part I) and 32 additional patients on dose expansion (part II). RP2D of palbociclib 100 mg on Day 2-22 + Cisplatin (cis) 60 mg/m2 IV on Day 1 Q4W (Arm A); and palbociclib 75 mg on Day 2-22 + Carboplatin (carbo) AUC 6 IV on Day 1 Q4W (Arm B). ORR for Part I were 12.5% (Arm A) and 25% (Arm B). Median PFS and OS for dose expansion were 2.1 and 4.9 months, respectively. For PDAC, mPFS was 1.9 months (95% CI: 1.7, 2.4), and OS was 3.7 months (95% CI: 2.7, 5.7). Most common treatment-related adverse events (TRAEs-all grade %): Arm A-neutropenia (66%), thrombocytopenia (26%), nausea, fatigue, and anemia (20% each); Arm B-neutropenia (64.7%), thrombocytopenia (53%), and anemia (29%). There were no grade 4-5 TRAEs.

Conclusions and relevance: The combination of palbociclib with cisplatin or carboplatin had an acceptable safety profile and clinical responses in some treatment refractory advanced cancers. There was no objective response, but about half of PDAC patients had disease stabilization. Additional efforts are needed to exploit CDK abnormalities in these patients. Clinical trial registration number: NCT02897375.

Keywords: CDK; clinical trial; palbociclib; pancreatic cancer; phase I; platinum.

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Conflict of interest statement

O.B.A. has declared the following conflicts: Research funding: Taiho Oncology, Ipsen Pharmaceuticals, GSK, Bristol Myers Squibb, Boehringer Ingelheim, Xencor Inc., ASCO, Cue Biopharma, Inc., Merck, Inhibitex Inc, Arcus Biosciences Inc., AstraZeneca, Loxo/Lilly Oncology; Consulting/advisory role: Ipsen Pharmaceuticals, GSK, Cue Biopharma, Inc., Abbvie, Taiho, Bristol Myers Squibb, AstraZeneca, Exelixis, Takeda, Boehringer Ingelheim, Loxo Oncology; Independent data monitoring committee: Compass Therapeutics, Inc. TKO reported research funding from Norvatis, Bayer, Regeneron, Astrazeneca, Amgen, Pfizer, Merck, Roche/Genentech, Cardiff Oncology, Ymabs, Boehringer Ingelheim and EMD Serono. TKO served as an advisor to Norvartis, Lilly, Eisai, BMS, Amgen, Astrazeneca, Bayer, Merck, Oncocyte, Takeda, Jazz, Zentalis, Ipsen, Beigene, Coherus.

Figures

Figure 1.
Figure 1.
Swimmer plot showing the length of duration of treatment for all the patients enrolled on both dose escalation and expansion.
Figure 2.
Figure 2.
Spider (A) and Waterfall plots (B) showing the best percent change from baseline (as assessed by the investigator) in target lesions for patients on the dose expansion cohort.
Figure 3.
Figure 3.
KM curves showing progression-free survival (A) and overall survival (B) for patients with PDAC.
See this image and copyright information in PMC

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