A Study of Pralsetinib Versus Standard of Care for First-Line Treatment of Advanced Non-Small Cell Lung Cancer (NSCLC) (AcceleRET-Lung)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

F. Hoffmann-La Roche AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

12 Jun 2020 → 28 Jan 2025

Decision date (initial)

2024-04-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

F. Hoffmann-La Roche AG

External identifiers

EU CT number

2023-505035-12-00

EudraCT number

2019-002463-10

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Others, Efficacy, Pharmacokinetic, Pharmacodynamic

To assess whether pralsetinib improves progression-free survival (PFS) as compared with Investigator's choice of platinum-containing anticancer treatment regimens for patients with RET fusion-positive metastatic NSCLC

Secondary objectives 4

1. To evaluate the efficacy of pralsetinib compared with investigator’s choice of SOC platinum containing anticancer treatment regimens with Corresponding Endpoint ORR (objective response rate)
2. To evaluate overall survival (OS)
3. To evaluate the safety and tolerability profile of pralsetinib as compared to investigator’s choice of SOC platinum containing anticancer treatment regimens
4. To compare additional measures of anticancer activity, including duration of response, disease control rate, and clinical benefit rate

Conditions and MedDRA coding

RET fusion−positive, metastatic Non-Small Cell Lung Cancer

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-002575-PIP01-19

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 1. Participant has pathologically or cytologically confirmed, definitively diagnosed, advanced unresectable NSCLC (i.e., Stage IIIB not eligible for definitive chemoradiotherapy) or metastatic NSCLC (i.e., Stage IV), per the Union Internationale Contre le Cancer/American Joint Committee on Cancer staging system (Amin et al. 2017) of either squamous or non-squamous histology based on the major histologic component that has not been treated with systemic anticancer therapy for metastatic disease
2. 2. Participant has documented RET fusion that must meet 1 of the following 2 criteria: a. Documented RET fusion using either tissue or plasma as performed by a Clinical Laboratory Improvement Amendments (CLIA)-certified or equivalent accredited diagnostic laboratory. b. Documented RET fusion by a positive result from tumor tissue testing performed centrally by Foundation Medicine (FMI) clinical trial assay or an alternate, approved central laboratory for that region
3. 3. Participant has measurable disease based on RECIST 1.1 as determined by the local site Investigator/radiology assessment. Lesions located in a previously irradiated area are considered measurable if progression has been demonstrated after irradiation
4. 4. Participants has an ECOG PS of 0-1
5. 5. Participants who have a negative HIV test at screening. If HIV positive, participant should be stable on anti-retroviral therapy with a CD4 count ≥ 200/µL, and have an undetectable viral load.
6. 6. Participant cannot have received any prior anticancer therapy for metastatic disease a. Participant can have received previous anticancer therapy (except a selective RET inhibitor) in the neoadjuvant or adjuvant setting but must have experienced an interval of at least ≥ 6 months from completion of therapy to recurrence b. Participant that received previous immune checkpoint inhibitors in the adjuvant or consolidation setting following chemoradiation are not allowed to receive pembrolizumab if randomized in Arm B

Exclusion criteria 6

1. 1. Participant’s tumor has any additional known primary driver alterations other than RET, such as targetable mutations of EGFR, ALK, ROS1, MET, and BRAF. Investigators should inform the Medical Monitor about the enrollment of participants with tumors having co-mutations
2. 2. Participant previously received treatment with a selective RET inhibitor.
3. 3. Participant received radiotherapy or radiosurgery to any site within 14 days before randomization or more than 30 Gy of radiotherapy to the lung in the 6 months before randomization.
4. 4. Participants with a medical condition that requires immunosuppression
5. 5. Participant has a history of another primary malignancy that has been diagnosed or required therapy within the past 3 years before randomization. The following prior malignancies are not exclusionary: completely resected basal cell and squamous cell skin cancer, curatively treated localized prostate cancer, curatively treated localized thyroid cancer, and completely resected carcinoma in situ of any site.
6. 6. Participant with a serious infection requiring systemic antibiotic therapy within 7 days prior to initiation of study treatment, or any active infection that, in the opinion of the investigator, could impact patient's safety

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1. PFS, defined as the time from randomization date to the first of documented progressive disease (PD), as assessed by investigator according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) or death due to any cause, whichever occurs first

Secondary endpoints 9

1. 1. Objective response rate (ORR) defined as the proportion of participants with a CR or a PR on two consecutive occasions ≥ 4 weeks apart, as assessed by investigator according to RECIST v1.1
2. 2. Overall survival (OS), defined as the time to randomization date to death due to any cause.
3. 3. Incidence and severity of adverse events, with severity, as determined according to the National Cancer Institute Common Toxicity Criteria for Adverse Events version 5.0
4. 4. Change from baseline in ECOG performance status
5. 5. Change from baseline in targeted vital signs
6. 6. Change from baseline in targeted clinical laboratory test results
7. 7. Duration of response (DOR), defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), as assessed by investigator according to RECIST v1.1
8. 8. Disease control rate (DCR), defined as the proportion of participants who experience a best response of CR, or PR, or SD, as assessed by investigator according to RECIST v1.1
9. 9. Clinical benefit rate (CBR), defined as the proportion of participants who experience a best response of SD with a minimum duration of 6 months, a CR, or a PR, as assessed by investigator according to RECIST v1.1

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 7

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

F. Hoffmann-La Roche AG

Sponsor organisation

F. Hoffmann-La Roche AG

Address

Grenzacherstrasse 124

City

Basel

Postcode

4058

Country

Switzerland

Scientific contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Public contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Third parties 8

Locations

10 EU/EEA countries · 48 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Urgent safety measures 1 · Art. 54 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 62 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications