A multi‑country oncology study regained momentum through structured transition planning, seamless cross‑functional collaboration and decisive operational oversight, regulatory recovery, and disciplined execution from approval to first patient enrolled.
SITUATION
A US-based biotechnology company appointed Pivotal S.L.U. to take over EU operations for a Phase 1/2 trial investigating a novel TRK inhibitor in patients with NTRK-fusion-positive advanced or metastatic solid tumors.
The study had previously been managed by another Global CRO, and the sponsor required a rapid and seamless transition to prevent further delays in sites activation and patient enrollment.
By the time of the transition in mid‑March 2022, initial regulatory approvals had already been obtained from most of the participating EU countries between September 2021 and January 2022. However, the former CRO had not initiated any sites, and the existing approvals did not allow enrollment under the sponsor’s updated development strategy.
Consequently, the sponsor required the submission and approval of a new protocol amendment to enable EU sites to initiate enrollment. Pivotal was therefore mandated to assume full responsibility and recover the program, moving it from stalled activation to the first patient enrolled.
STUDY OVERVIEW
CHALLENGES
Pivotal inherited a study that presented several operational and timeline risks. The following issues required immediate action.
| 1. Dormant Approvals with No Execution Regulatory approvals had been issued between September 2021 and January 2022. However, these approvals did not allow enrollment under the updated strategy. At the time of the handover in March 2022, no EU site had been initiated. |
| 2. Mandatory Protocol Amendment The sponsor required a new protocol amendment. This amendment had to be submitted and approved in all participating EU countries before sites could start enrollment. |
| 3. Downstream contractual impact The new amendment also required updates to all existing CTAs. As a result, each site needed contractual renegotiation before activation. |
| 4. Extended gap between approval and activation The long delay between initial approvals and operational readiness increased the risk of site disengagement and loss of interest. |
| 5. Multi-country regulatory recovery Each EU country required a customized approach for amendment submission and approval. Timelines were tight, and coordination needed to be precise. |
| 6. Complex stakeholder coordination Sponsor teams, legacy CRO documentation, and local partners required clear alignment. This alignment needed to happen quickly to restore study control and momentum. |
SOLUTION
Pivotal implemented a structured recovery and transition plan that focused on converting regulatory status into operational execution.
Following the initiation of the transition, Pivotal led the regulatory recovery strategy, which included preparing and submitting the required protocol amendment while reestablishing site readiness and investigator engagement.
Weekly governance meetings, micromanagement at the country level, and disciplined planning enabled the study to progress from stalled approvals to active enrollment.
Regulatory Recovery:
- Comprehensive reassessment of existing approvals and identification of regulatory gaps that were preventing site initiation.
- Preparation and submission of a new protocol amendment managed by Pivotal and required by the sponsor, to enable EU site initiation and enrollment.
- Following a rapid preparation and submission phase led by Pivotal shortly after transition completion, regulatory approvals enabling full site initiation were obtained on a rolling basis across countries.
- Parallel management of CTA amendments, aligned with protocol amendment approvals, to ensure that contractual readiness would not delay site initiation once regulatory clearance was obtained.
- Clear weekly milestones and KPIs were established to track regulatory progress, document readiness, and site activation timelines.
Operational Execution:
- Comprehensive study onboarding and training, including the protocol, procedures, eCRF/eTMF, IMP handling, and SIV readiness.
- Full site start-up prioritization, moving sites from approval status to initiation readiness.
- Strong CRA and country coordinator engagement to reactivate investigators and site teams.
- Accelerated CTA and budget negotiations, aligned with renewed activation timelines.
RESULTS
Pivotal successfully rescued and relaunched the EU portion of this clinical trial through disciplined project management, regulatory recovery, operational execution, and strong multi-stakeholder coordination.
Key achievements:
- Full transition was completed by June 2022, aligning with the initial plan.
- Protocol amendment preparation and submissions were completed in all required countries within weeks of the transition’s completion, enabling countries to progress rapidly toward site activation and enrollment.
- Protocol amendment approvals enabling full EU site initiation were obtained on a rolling basis across participating countries under Pivotal’s management.
- Regulatory and contractual readiness was achieved in parallel to prevent additional delays to site initiation following protocol amendment approval.
- From a starting point where no EU sites had been initiated at handover, Pivotal rapidly rebuilt site readiness, enabling the first Site Initiation Visits (SIVs) to take place within few months from transition.
- The first EU subject was enrolled shortly thereafter, marking a full recovery from stalled execution to active enrollment.
- Sustained site engagement and activation restored confidence after a prolonged inactive period.
- Study momentum was fully restored, avoiding the cancellation or extended delay of a complex, multi-country oncology program.
CONCLUSION
The successful rescue of this study demonstrates Pivotal’s ability to recover complex clinical programs in which regulatory progress has not translated into execution.
By spearheading a mandatory protocol amendment, converting dormant approvals into active sites, and enrolling the first EU patient, Pivotal executed a disciplined, high-quality relaunch.
This reestablished the study’s credibility, restored the sponsor’s confidence, and secured a sustainable path forward for this critical oncology development program.
MEDIA CONTACT
Ms. Natalia Farr
