Trial · NCT03037385
Phase 1/2 Study of the Highly-selective RET Inhibitor, Pralsetinib (BLU-667), in Participants With Thyroid Cancer, Non-Small Cell Lung Cancer, and Other Advanced Solid Tumors
NCT03037385, Phase 1, Phase 2, Completed, Hoffmann-La Roche; results first posted 2025-05-31
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. Phase 1/2 Study of the Highly-selective RET Inhibitor, Pralsetinib (BLU-667), in Participants With Thyroid Cancer, Non-Small Cell Lung Cancer, and Other Advanced Solid Tumors. Trials, record NCT03037385. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT03037385
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- Phase 1/2 Study of the Highly-selective RET Inhibitor, Pralsetinib (BLU-667), in Participants With Thyroid Cancer, Non-Small Cell Lung Cancer, and Other Advanced Solid Tumors
- NCT number
- NCT03037385
- Status
- Completed
- Phases
- Phase 1, Phase 2
- Enrollment
- 590 participants, actual
- Lead sponsor
- Hoffmann-La Roche
- Conditions
RET-altered Non Small Cell Lung Cancer, Medullary Thyroid Cancer, RET-altered Papillary Thyroid Cancer, RET-altered Colon Cancer, RET-altered Solid Tumors, Lung Neoplasm, Carcinoma, Non-Small-Cell Lung, Thyroid Diseases, Thyroid Neoplasm, Thyroid Cancer, Papillary, Carcinoma, Neuroendocrine, Respiratory Tract Neoplasms, Thoracic Neoplasms, Neoplasms by Site, Neoplasms, Lung Diseases, Respiratory Tract Disease, Carcinoma, Bronchogenic, Bronchial Neoplasms, Endocrine System Diseases, Endocrine Gland Neoplasm, Head and Neck Neoplasms, Adenocarcinoma, Papillary, Adenocarcinoma, Carcinoma, Neoplasms, Glandular and Epithelial, Neoplasms by Histologic Type, Neuroendocrine Tumors, Neuroectodermal Tumors, Neoplasms, Germ Cell and Embryonal, Neoplasms, Nerve Tissue, Colonic Neoplasms, Colorectal Neoplasms, Intestinal Neoplasms, Gastrointestinal Neoplasms, Digestive System Neoplasm, Digestive System Disease, Gastrointestinal Disease, Colonic Diseases, Intestinal Disease
- Interventions
- pralsetinib (BLU-667)
- First posted
- 2017-01-31
- Last updated
- 2025-05-31
- Other registries' IDs
- eudract:2016-004390-41
- Results first posted
- 2025-05-31
Source ClinicalTrials.gov
Registered outcomes44
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Phase 1 : Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Pralsetinib | Up to approximately 30.8 months | MTD was defined as the highest tolerated dose of pralsetinib without causing dose limiting toxicities (DLTs). DLT was defined as any Grade ≥3 adverse event (AE) occurring during Cycle 1 during Phase 1 (dose escalation) that is not clearly caused by something other than pralsetinib. RP2D was defined as the highest dose with acceptable toxicity as determined from dose-escalation phase. |
| Primary | Phase 1 and Phase 2: Number of Participants With AEs and Serious AEs (SAEs) | From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) | An AE was any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality. A SAE is any significant hazard, contraindication, side effect that is fatal or life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly or birth defect, is medically significant or requires intervention to prevent one or other of the outcomes listed above. |
| Primary | Phase 2: Overall Response Rate (ORR) | Up to approximately 79.8 months | ORR was defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) for at least two assessments with at least 28 days apart and no disease progression (PD) in between. Per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1), CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in the short axis to \<10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters (SOD) of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline). ORR and its two-sided 95% CI, based on the exact binomial distribution (Clopper-Pearson), were presented. |
| Secondary | Phase 1: ORR | Up to approximately 28 months | ORR was defined as the percentage of participants with a confirmed CR or PR for at least two assessments with at least 28 days apart and no PD in between. Per RECIST v1.1, CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in the short axis to \<10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline). ORR and its two-sided 95% CI, based on the exact binomial distribution (Clopper-Pearson), was presented. |
| Secondary | Phase 1 and Phase 2: ORR in RET-fusion Positive NSCLC Participants With Specific RET Gene Status | Up to approximately 79.8 months | Oncogenic RET rearrangements have been identified in 1%-2% of NSCLC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., Kinesin family member 5B (KIF5B), coiled-coil domain containing 6 (CCDC6), nuclear receptor coactivator 4 (NCOA4)). RET genotypes were determined by local testing and/or central analysis of circulating tumor deoxyribonucleic acid (ctDNA). ORR was assessed in participants having specific RET rearrangements. ORR was defined as the percentage of participants with a confirmed CR or PR for at least 2 assessments with at least 28 days apart and no PD in between. CR, PR, and PD were defined per RECIST as outlined in the description for OM 3. |
| Secondary | Phase 1 and Phase 2: ORR in RET-mutation MTC Participants With Specific RET Gene Status | Up to approximately 79.8 months | Oncogenic RET activation has been implicated as a driver in MTC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., M918T, cysteine rich domain, V804X). RET genotypes were determined by local testing and/or central analysis of ctDNA. ORR was assessed in participants having specific RET rearrangements. ORR was defined as the percentage of participants with a confirmed CR or PR for at least 2 assessments with at least 28 days apart and no PD in between. CR, PR, and PD were defined per RECIST as outlined in the description for OM 3. |
| Secondary | Phase 1 and Phase 2: ORR in RET-fusion Positive TC Participants With Specific RET Gene Status | Up to approximately 79.8 months | Oncogenic RET activation has been implicated as a driver in both MTC and differentiated TC (DTC). These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., KIF5B, CCDC6, NCOA4). RET genotypes were determined by local testing and/or central analysis of ctDNA. ORR was assessed in participants having specific RET rearrangements. ORR was defined as the percentage of participants with a confirmed CR or PR for at least 2 assessments with at least 28 days apart and no PD in between. CR, PR, and PD were defined per RECIST as outlined in the description for OM 3. |
| Secondary | Phase 1 and Phase 2: Clinical Benefit Rate (CBR) in RET-fusion Positive NSCLC Participants With Specific RET Gene Status | Up to approximately 79.8 months | Oncogenic RET rearrangements have been identified in 1%-2% of NSCLC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., KIF5B, CCDC6, NCOA4). RET genotypes were determined by local testing and/or central analysis of ctDNA. CBR was assessed in participants having specific RET rearrangements. CBR was defined as the percentage of participants with a confirmed CR or PR, or stable disease (SD) which has been lasting at least 16 weeks (i.e. 4 cycles if 28 days are in one cycle) from the first dose date. CR and PR were defined per RECIST as outlined in the description for OM 3. SD was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline). |
| Secondary | Phase 1 and Phase 2: CBR in RET-mutation MTC Participants With Specific RET Gene Status | Up to approximately 79.8 months | Oncogenic RET activation has been implicated as a driver in MTC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., M918T, cysteine rich domain, V804X). RET genotypes were determined by local testing and/or central analysis of ctDNA. CBR was assessed in participants having specific RET rearrangements. CBR was defined as the percentage of participants with a confirmed CR or PR, or SD which has been lasting at least 16 weeks (i.e. 4 cycles if 28 days are in one cycle) from the first dose date. CR and PR were defined per RECIST as outlined in the description for OM 3. SD was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline). |
| Secondary | Phase 1 and Phase 2: CBR in RET-fusion Positive TC Participants With Specific RET Gene Status | Up to approximately 79.8 months | Oncogenic RET activation has been implicated as a driver in both MTC and DTC. These rearrangements typically produce chimeric transcripts that encode a fusion protein consisting of the RET kinase domain coupled to a protein with a dimerization domain (e.g., KIF5B, CCDC6, NCOA4). RET genotypes were determined by local testing and/or central analysis of ctDNA. CBR was assessed in participants having specific RET rearrangements. CBR was defined as the percentage of participants with a confirmed CR or PR or SD which has been lasting at least 16 weeks (i.e. 4 cycles if 28 days are in one cycle) from the first dose date. CR and PR were defined per RECIST as outlined in the description for OM 3. SD was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. PD was defined as at least a 20% increase in SOD of target lesions, taking as reference the smallest SOD on study (including baseline). |
1 to 10 of 44Source ClinicalTrials.gov
See all 44 registered outcomesOutcomes44
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Phase 1 : Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Pralsetinib | Up to approximately 30.8 months | Dose-determining population included all participants in the dose-escalation part who have received ≥75% (21 days) of the study drug and completed safety evaluations through Cycle 1 Day 28 or experienced a DLT. | mg | NUMBER |
| PRIMARY | Phase 1 and Phase 2: Number of Participants With AEs and Serious AEs (SAEs) | From Cycle 1 Day 1 up to 30 days after the final dose of study drug (up to approximately 6.7 years) | Safety Population included all participants who have received at least 1 dose of the study drug regardless of starting dose levels. As pre-specified in the SAP, safety data was to be analyzed and reported as per the pre-planned grouped dose level II (SAP section 3.6.5.2). Hence, per dose safety data is not presented for this study. | percentage of participants | NUMBER |
| PRIMARY | Phase 2: Overall Response Rate (ORR) | Up to approximately 79.8 months | RET-altered measurable disease population included participants in the efficacy population who had measurable (target) disease per RECIST v1.1 at baseline according to blinded central review (BICR) and sufficient evidence of a RET alteration. As prespecified in the SAP, Phase 1 participants treated at 400 mg QD are also included in Phase 2 efficacy analysis. | percentage of participants | NUMBER |
| SECONDARY | Phase 1: ORR | Up to approximately 28 months | Efficacy population included all participants who have been exposed to at least one dose of the study drug on or prior to 11 July 2019. | percentage of participants | NUMBER |
| SECONDARY | Phase 1 and Phase 2: ORR in RET-fusion Positive NSCLC Participants With Specific RET Gene Status | Up to approximately 79.8 months | RET-altered measurable disease population included participants in the efficacy population who have measurable (target) disease per RECIST v1.1, at baseline according to BICR and sufficient evidence of a RET alteration. As prespecified in the SAP, Phase 1 participants treated at 400 mg QD are pooled with Phase 2 participants for efficacy analysis. Number analyzed is the number of participants with the specified mutation. | percentage of participants | NUMBER |
| SECONDARY | Phase 1 and Phase 2: ORR in RET-mutation MTC Participants With Specific RET Gene Status | Up to approximately 79.8 months | RET-altered measurable disease population included participants in the efficacy population who have measurable (target) disease per RECIST v1.1, at baseline according to BICR and sufficient evidence of a RET alteration. As prespecified in the SAP, Phase 1 participants treated at 400 mg QD are pooled with Phase 2 participants for efficacy analysis. Number analyzed is the number of participants with the specified mutation. | percentage of participants | NUMBER |
| SECONDARY | Phase 1 and Phase 2: ORR in RET-fusion Positive TC Participants With Specific RET Gene Status | Up to approximately 79.8 months | RET-altered measurable disease population included participants in the efficacy population who have measurable (target) disease per RECIST v1.1, at baseline according to BICR and sufficient evidence of a RET alteration. As prespecified in the SAP, Phase 1 participants treated at 400 mg QD are pooled with Phase 2 participants for efficacy analysis. Number analyzed is the number of participants with the specified mutation. | percentage of participants | NUMBER |
| SECONDARY | Phase 1 and Phase 2: Clinical Benefit Rate (CBR) in RET-fusion Positive NSCLC Participants With Specific RET Gene Status | Up to approximately 79.8 months | RET-altered measurable disease population included participants in the efficacy population who have measurable (target) disease per RECIST v1.1, at baseline according to BICR and sufficient evidence of a RET alteration. As prespecified in the SAP, Phase 1 participants treated at 400 mg QD are pooled with Phase 2 participants for efficacy analysis. Number analyzed is the number of participants with the specified mutation. | percentage of participants | NUMBER |
| SECONDARY | Phase 1 and Phase 2: CBR in RET-mutation MTC Participants With Specific RET Gene Status | Up to approximately 79.8 months | RET-altered measurable disease population included participants in the efficacy population who have measurable (target) disease per RECIST v1.1, at baseline according to BICR and sufficient evidence of a RET alteration. As prespecified in the SAP, Phase 1 participants treated at 400 mg QD are pooled with Phase 2 participants for efficacy analysis. Number analyzed is the number of participants with the specified mutation. | percentage of participants | NUMBER |
| SECONDARY | Phase 1 and Phase 2: CBR in RET-fusion Positive TC Participants With Specific RET Gene Status | Up to approximately 79.8 months | RET-altered measurable disease population included participants in the efficacy population who have measurable (target) disease per RECIST v1.1, at baseline according to BICR and sufficient evidence of a RET alteration. As prespecified in the SAP, Phase 1 participants treated at 400 mg QD are pooled with Phase 2 participants for efficacy analysis. Number analyzed is the number of participants with the specified mutation. | percentage of participants | NUMBER |
1 to 10 of 44Source ClinicalTrials.gov
See all 44 outcomesResults by group375
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Phase 1 : Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Pralsetinib | Phase 1: All Participants QD | MTD | 400 | mg | |
| Phase 1 : Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Pralsetinib | Phase 1: All Participants QD | RP2D | 400 | mg | |
| Phase 1 and Phase 2: Number of Participants With AEs and Serious AEs (SAEs) | Pralsetinib ≤ 300 mg QD | AEs | 37 | percentage of participants | |
| Phase 1 and Phase 2: Number of Participants With AEs and Serious AEs (SAEs) | Pralsetinib 400 mg QD | AEs | 540 | percentage of participants | |
| Phase 1 and Phase 2: Number of Participants With AEs and Serious AEs (SAEs) | Pralsetinib BID Dosing Schedule | AEs | 9 | percentage of participants | |
| Phase 1 and Phase 2: Number of Participants With AEs and Serious AEs (SAEs) | Pralsetinib All Doses | AEs | 590 | percentage of participants | |
| Phase 1 and Phase 2: Number of Participants With AEs and Serious AEs (SAEs) | Pralsetinib ≤ 300 mg QD | SAEs | 26 | percentage of participants | |
| Phase 1 and Phase 2: Number of Participants With AEs and Serious AEs (SAEs) | Pralsetinib 400 mg QD | SAEs | 381 | percentage of participants | |
| Phase 1 and Phase 2: Number of Participants With AEs and Serious AEs (SAEs) | Pralsetinib BID Dosing Schedule | SAEs | 7 | percentage of participants | |
| Phase 1 and Phase 2: Number of Participants With AEs and Serious AEs (SAEs) | Pralsetinib All Doses | SAEs | 416 | percentage of participants |
1 to 10 of 375Source ClinicalTrials.gov
See all 375 results by groupParticipant flow30
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Overall Study | STARTED | Phase I: Pralsetinib 30 mg | 2 | |
| Overall Study | STARTED | Phase I: Pralsetinib 60 mg | 6 | |
| Overall Study | STARTED | Phase I: Pralsetinib 100 mg | 5 | |
| Overall Study | STARTED | Phase I: Pralsetinib 200 mg | 13 | |
| Overall Study | STARTED | Phase I: Pralsetinib 300 mg | 11 | |
| Overall Study | STARTED | Phase I: Pralsetinib 400 mg | 12 | |
| Overall Study | STARTED | Phase I: Pralsetinib 600 mg | 4 | |
| Overall Study | STARTED | Phase I: Pralsetinib 100/100 mg | 5 | |
| Overall Study | STARTED | Phase I: Pralsetinib 200/100 mg | 4 | |
| Overall Study | STARTED | Phase II: Pralsetinib 400 mg | 528 |
1 to 10 of 30Source ClinicalTrials.gov
See all 30 participant flowAdverse events2,068
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Anaemia | Blood and lymphatic system disorders | Pralsetinib ≤ 300 mg QD | 16 | 37 | 45 |
| other | Anaemia | Blood and lymphatic system disorders | Pralsetinib 400 mg QD | 285 | 540 | 1,098 |
| other | Anaemia | Blood and lymphatic system disorders | Pralsetinib BID Dosing Schedule | 6 | 9 | 15 |
| other | Anaemia | Blood and lymphatic system disorders | Pralsetinib All Doses | 310 | 590 | 1,168 |
| other | Leukopenia | Blood and lymphatic system disorders | Pralsetinib ≤ 300 mg QD | 4 | 37 | 11 |
| other | Leukopenia | Blood and lymphatic system disorders | Pralsetinib 400 mg QD | 55 | 540 | 226 |
| other | Leukopenia | Blood and lymphatic system disorders | Pralsetinib BID Dosing Schedule | 1 | 9 | 1 |
| other | Leukopenia | Blood and lymphatic system disorders | Pralsetinib All Doses | 61 | 590 | 239 |
| other | Lymphopenia | Blood and lymphatic system disorders | Pralsetinib ≤ 300 mg QD | 7 | 37 | 29 |
| other | Lymphopenia | Blood and lymphatic system disorders | Pralsetinib 400 mg QD | 67 | 540 | 321 |
1 to 10 of 2,068Source ClinicalTrials.gov
See all 2,068 adverse eventsAdverse event totals12
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Pralsetinib ≤ 300 mg QD | 15 | 37 |
| Total, all-cause mortality | Pralsetinib 400 mg QD | 245 | 540 |
| Total, all-cause mortality | Pralsetinib BID Dosing Schedule | 7 | 9 |
| Total, all-cause mortality | Pralsetinib All Doses | 268 | 590 |
| Total, other adverse events | Pralsetinib ≤ 300 mg QD | 36 | 37 |
| Total, other adverse events | Pralsetinib 400 mg QD | 536 | 540 |
| Total, other adverse events | Pralsetinib BID Dosing Schedule | 9 | 9 |
| Total, other adverse events | Pralsetinib All Doses | 585 | 590 |
| Total, serious adverse events | Pralsetinib ≤ 300 mg QD | 26 | 37 |
| Total, serious adverse events | Pralsetinib 400 mg QD | 381 | 540 |
1 to 10 of 12Source ClinicalTrials.gov
See all 12 adverse event totalsPapers10
The papers the trial lists on ClinicalTrials.gov.
Grants0
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
None in this release.
Trial comparisons0
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
None in this release.
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
For software
Read this trial from software.
The record and each of its lists are JSON, twenty rows a page. No key.
GET https://conductscience.org/api/trials/v1/NCT03037385
GET https://conductscience.org/api/trials/v1/NCT03037385/registered?page=2