Savolitinib plus osimertinib versus platinum-based doublet chemotherapy in participants with Non-Small Cell Lung Cancer who have progressed on Osimertinib treatment - SAFFRON

Study identifier:D5087C00001

ClinicalTrials.gov identifier:NCT05261399

EudraCT identifier:2021-006374-24

CTIS identifier:N/A

Recruiting

Official Title

A Phase III, Randomised, Open-Label Study of Savolitinib in Combination With Osimertinib Versus Platinum-Based Doublet Chemotherapy in Participants With EGFR Mutated, MET-Overexpressed and/or Amplified, Locally Advanced or Metastatic Non-Small Cell Lung Cancer Who Have Progressed on Treatment With Osimertinib (SAFFRON).

Medical condition

Carcinoma

Phase

Phase 3

Healthy volunteers

Study drug

Savolitinib, Osimertinib, Pemetrexed, Cisplatin, Carboplatin

Sex

All

Estimated Enrollment

324

Study type

Interventional

Age

18 Years - 130 Years

Date

Study Start Date: 03 Aug 2022

Estimated Primary Completion Date: 30 May 2025

Estimated Study Completion Date: 30 Nov 2026

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Mar 2024 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

- Provision of signed and dated written ICF prior to any mandatory and non-mandatory study-specific procedures, sampling and analyses.
- Participant must be ≥18 years (≥ 19 years of age in South Korea) at the time of signing the informed consent. All genders are permitted.
- Histologically or cytologically confirmed locally advanced or metastatic NSCLC which is not amenable to curative therapy.
- Must have at least one documented sensitising EGFR mutation: exon19 deletion, L858R mutation, and/or T790M.
- Documented radiologic progression on first- or second-line treatment with osimertinib as the most recent anti-cancer therapy.
- Mandatory provision of FFPE tumour tissue.
- MET overexpression and/or amplification in tumour specimen collected following progression on prior osimertinib treatment.
- Measurable disease as defined by RECIST 1.1.
- Adequate haematological, liver, renal and cardiac functions, and coagulation parameters.
- ECOG performance status of 0 or 1.

Exclusion Criteria

- Predominant squamous NSCLC, and small cell lung cancer.
- Prior or current treatment with a third-generation EGFR-TKI other than Osimertinib.
- Prior or current treatment with savolitinib or another MET inhibitors.
- Spinal cord compression or brain metastases, unless asymptomatic and are stable.
- History or active leptomeningeal carcinomatosis.
- Unresolved toxicities from any prior therapy greater than CTCAE Grade 1 and prior platinum-therapy related Grade 2 neuropathies with the exception of alopecia and haemoglobin ≥ 9.0 g/dL.
- Active/unstable cardiac diseases currently or within the last 6 months, clinically significant ECG abnormalities, and/or factors/medications that may affect QTc intervals.
- History of liver cirrhosis of any origin and clinical stage; or history of other serious liver disease or chronic disease with relevant liver involvement.
- Known serious active infection including, but not limited to, tuberculosis, or HIV, HBV or HCV or gastrointestinal disease.
- Receipt of live attenuated vaccine (including against COVID-19) within 30 days prior to the first dose of study intervention.
- Past medical history of ILD, drug-induced ILD, radiation pneumonitis, which required steroid treatment, or any evidence of clinically active ILD.
- Participants currently receiving medications or herbal supplements known to be strong inducers of cytochrome P450 (CYP)3A4 or strong inhibitors of CYP1A2.

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Arms	Assigned Interventions
Active Comparator: Chemotherapy Pemetrexed (500 mg/m2) with either cisplatin (75 mg/m2) or carboplatin (AUC5) on Day 1 of 21-day cycles (Q3W) for 4 cycles, followed by pemetrexed maintenance (500 mg/m2) Q3W	Drug: Pemetrexed Pemetrexed (500 mg/m2) Administrative route : IV infusion Other Name: NAP Drug: Cisplatin Cisplatin (75 mg/m2) or Administrative route : IV infusion Other Name: NAP Drug: Carboplatin Carboplatin (AUC5) Administrative route : IV infusion Other Name: NAP
Experimental: Savolitinib + Osimertinib 300 mg savolitinib BID plus 80 mg osimertinib QD	Drug: Savolitinib 300 mg savolitinib (3 × 100 mg tablets twice daily) Administrative route : oral Other Name: AZD6094, HMPL-504, volitinib Drug: Osimertinib 80 mg osimertinib (1 × 80 mg tablet once daily) Administrative route : oral Other Name: AZD9291, Tagrisso

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]

Investigators

Principal Investigator

Shun Lu

Shanghai Chest Hospital, Shanghai JiaoTong University, #241 Huai Hai Road (west), Shanghai, China.