Clinical Trials Logo

Clinical Trial Summary

This is a single centre non-randomised open label phase 1 trial of lung SBRT to part of a lung lesion in patients with advanced NSCLC in combination with pembrolizumab. This study will recruit up to 24 patients whose lung cancer has progressed beyond one line of palliative chemotherapy, and an EGFR or ALK inhibitor if an EGFR driver mutation or ALK gene rearrangement is present, respectively, and now requires further palliative systemic treatment.


Clinical Trial Description

The study will be conducted in two parts; an initial lung SBRT dose escalation phase (Part A), followed by a lung SBRT dose expansion cohort (Part B). The dose escalation phase is based on a 3+3 design such that patients will be treated in cohorts of 3-6 patients. A maximum of 12 patients will be allocated to one of two doses of lung SBRT in combination with pembrolizumab to determine the MTD, DLTs and RP2D. If there is more than one DLT in cohort 1, this treatment combination will be deemed as being unacceptable, and it would lead to termination of the study. Note, there is no de-escalation in cohort 1. During the dose expansion cohort, 12 patients will have lung SBRT dosed at the RP2D determined during the dose escalation phase in combination with pembrolizumab to obtain additional safety and response data. Maintenance pembrolizumab will continue until disease progression, unacceptable toxicities, the patient withdraws consent to the trial, or the patient has completed 24 months of treatment. A maximum of 24 patients will be treated in the study.

All patients will receive pembrolizumab on cycle (C) 1 day (D) 1, in Part A and B of the study. All patients will receive lung SBRT on C1D15, C1D17, and C1D19 as per lung SBRT protocol. Although C1D1 can occur +/- 3 days, C1D15, C1D17, and C1D19, must be scheduled for a Monday, Wednesday and Friday, respectively. Patients in part A will receive lung SBRT dosed at 30 Gy in 3# in cohort 1, or 54 Gy in 3# in cohort 2. Patients in Part B will receive the RP2D of lung SBRT, determined in Part A. All patients in Part A and Part B will receive pembrolizumab dosed at 200 mg every 3 weeks, until disease progression, unacceptable toxicities, the patient withdraws consent from the trial, or the patient has completed 24 months of treatment.

In the dose escalation phase, a minimum of 3 patients will be required per dose level being assessed. A minimum gap of 1 week will be left between the treatment of the first and the second, and between the second and the third patients with the combination of pembrolizumab and lung SBRT to mitigate against multiple patients suffering from acute toxicity. The DLT period for this study is 12 weeks from the last dose of lung SBRT (i.e. at C6D1). The dose escalation will be considered by the Safety Review Committee (SRC) once the 3rd or 6th patient in the cohort has completed the DLT period. If no DLT is observed at a dose level,then lung SBRT will be dose escalated to the next dosing level (see Table 1). If 1 out of 3 patients experience a DLT, then the cohort will be expanded to 6 patients. If 1 in 6 patients experience a DLT, then the dose will be escalated to the next dosing level. However, if ≥ 2 in 6 patients experience a DLT then the maximum administered dose (MAD) will have been reached, and the RP2D will be the previous dosing level that will be used for the dose expansion cohorts. If the MAD is seen at dose level 1 then the study will be terminated. While waiting for 3 or 6 patients to complete the DLT period, no additional patients will be recruited. Further patients can only be recruited after the SRC has reviewed the toxicity data for the cohort and taken a decision to dose escalate to the next cohort or expand the current cohort to 6 patients.

Once the MTD has been determined the trial enters the dose expansion phase (unless the MTD is dose level 1). Here, 12 patients will be treated with the RP2D of SBRT combined with pembrolizumab.

If there is ongoing clinical benefit at 24 months, the CI/PI will need to discuss with the sponsor and MSD, on a case by case basis for the continuation of pembrolizumab. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT03368222
Study type Interventional
Source Royal Marsden NHS Foundation Trust
Contact Andrea Pejenaute
Phone 02089156667
Email priming.trial@rmh.nhs.uk
Status Not yet recruiting
Phase Phase 1
Start date January 2018
Completion date May 2021

See also
  Status Clinical Trial Phase
Recruiting NCT05094804 - A Study of OR2805, a Monoclonal Antibody Targeting CD163, Alone and in Combination With Anticancer Agents Phase 1/Phase 2
Recruiting NCT05707286 - Pilot Study to Determine Pro-Inflammatory Cytokine Kinetics During Immune Checkpoint Inhibitor Therapy
Recruiting NCT04258137 - Circulating DNA to Improve Outcome of Oncology PatiEnt. A Randomized Study N/A
Completed NCT01945021 - Phase II Safety and Efficacy Study of Crizotinib in East Asian Patients With ROS1 Positive, ALK Negative Advanced NSCLC Phase 2
Completed NCT04487457 - Prospective Study to Evaluate the Blood Kinetics of Immune Cells and Immunosuppressive Cytokines After Exposure to an Immunity Checkpoint Inhibitor (ICI): Study of the Impact of Chemotherapy
Terminated NCT04022876 - A Study of ALRN-6924 for the Prevention of Chemotherapy-induced Side Effects (Chemoprotection) Phase 1
Recruiting NCT05898763 - TEIPP Immunotherapy in Patients With NSCLC Phase 1/Phase 2
Recruiting NCT05532696 - Phase 1b/2 Study to Evaluate ABT-101 in Solid Tumor and NSCLC Patients Phase 1/Phase 2
Completed NCT04311034 - A Study of RC48-ADC in Subjects With Advanced Non-small Cell Lung Cancer Phase 1/Phase 2
Active, not recruiting NCT03177291 - Pirfenidone Combined With Standard First-Line Chemotherapy in Advanced-Stage Lung NSCLC Phase 1
Terminated NCT03257722 - Pembrolizumab + Idelalisib for Lung Cancer Study Phase 1/Phase 2
Completed NCT00349089 - Trial on Refinement of Early Stage Lung Cancer Adjuvant Therapy Phase 2
Completed NCT05116891 - A Phase 1/2 Study of CAN04 in Combination With Different Chemotherapy Regimens in Subjects With Advanced Solid Tumors Phase 1/Phase 2
Recruiting NCT04571632 - Clinical Trial of SBRT and Systemic Pembrolizumab With or Without Avelumab/Ipilimumab+ Dendritic Cells in Solid Tumors Phase 2
Terminated NCT03599518 - DS-1205c With Gefitinib for Metastatic or Unresectable Epidermal Growth Factor Receptor (EGFR)-Mutant Non-Small Cell Lung Cancer Phase 1
Not yet recruiting NCT06020989 - Lazertinib and Chemotherapy Combination in EGFR-mutant NSCLC Patients Without ctDNA Clearance After lead-in Lazertinib Monotherapy Phase 2
Withdrawn NCT03982134 - PDR001 + Panobinostat for Melanoma and NSCLC Phase 1
Withdrawn NCT03574649 - QUILT-2.024: Phase 2 Neoadjuvant, Consolidation, and Adjuvant Combination NANT Immunotherapy Versus Standard of Care in Subjects With Resectable Non-small Cell Lung Cancer Phase 2
Withdrawn NCT02844140 - DE-CT in Lung Cancer Proton Therapy N/A
Completed NCT03780010 - Study of TRC105 + Paclitaxel/Carboplatin and Bevacizumab in Patients With NSCLC Phase 1