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SAFFRON: Savolitinib Plus Osimertinib Versus Platinum-based Doublet Chemotherapy in Participants With Non-Small Cell Lung Cancer Who Have Progressed on Osimertinib Treatment

Sponsor
AstraZeneca (Industry)
Overall Status
Not yet recruiting
CT.gov ID
NCT05261399
Collaborator
(none)
324
Enrollment
79
Locations
2
Arms
52.1
Anticipated Duration (Months)
4.1
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Clinical study to investigate the efficacy and safety 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 NSCLC who have progressed on treatment with Osimertinib.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

This is a multicentre, Phase III, randomised, open-label study to investigate the efficacy and safety of savolitinib administered orally in combination with osimertinib versus platinum-based doublet chemotherapy in participants with EGFR mutated, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC who have progressed on first- or second-line treatment with osimertinib as the most recent therapy.

Approximately 324 participants with EGFR mutated, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC will be randomly assigned to study intervention with 1:1 ratio.

Patients will be treated until either objective progression of disease (PD) by Response Evaluation Criteria in Solid Tumours 1.1 (RECIST 1.1) is assessed by the investigator, unacceptable toxicity occurs, consent is withdrawn, or another discontinuation criterion is met.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
324 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Parallel AssignmentParallel Assignment
Masking:
None (Open Label)
Masking Description:
Open label
Primary Purpose:
Treatment
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).
Anticipated Study Start Date :
Jul 29, 2022
Anticipated Primary Completion Date :
Jul 15, 2025
Anticipated Study Completion Date :
Nov 30, 2026

Arms and Interventions

Arm Intervention/Treatment
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 Names:
  • NAP

    • Drug: Cisplatin
    Cisplatin (75 mg/m2) or Administrative route : IV infusion
    Other Names:
  • NAP

    • Drug: Carboplatin
    Carboplatin (AUC5) Administrative route : IV infusion
    Other Names:
  • 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 Names:
  • AZD6094, HMPL-504, volitinib

    • Drug: Osimertinib
    80 mg osimertinib (1 × 80 mg tablet once daily) Administrative route : oral
    Other Names:
  • AZD9291, Tagrisso

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Progression-free survival (PFS) / savolitinib + osimertinib versus platinum doublet chemotherapy in participants with EGFR mutated, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC who have progressed on osimertinib. [Approximately 55 months post first subject randomized]

      Defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause.

    Secondary Outcome Measures

    1. Overall Survival (OS) /savolitinib + osimertinib versus platinum doublet chemotherapy in participants with EGFR mutated, MET-overexpressed and/or amplified locally advanced or metastatic NSCLC who have progressed on treatment with osimertinib. [Approximately 55 months post first subject randomized.]

      Defined as time from randomisation until the date of death due to any cause.

    2. Progression-free survival (PFS) / savolitinib + osimertinib versus platinum doublet chemotherapy in participants with EGFR mutated, MET-overexpressed, locally advanced or metastatic NSCLC who have progressed on treatment with osimertinib. [Approximately 55 months post first subject randomized]

      Defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause.

    3. Overall Survival (OS) / savolitinib in combination with osimertinib versus platinum doublet chemotherapy in participants with EGFR mutated, MET-overexpressed by IHC, locally advanced or metastatic NSCLC who have progressed on treatment with osimertinib. [Approximately 55 months post first subject randomized]

      Defined as time from randomisation until the date of death due to any cause.

    4. Objective response rate (ORR) savolitinib + osimertinib versus platinum doublet chemotherapy in participants with EGFR mutated, MET-overexpressed and/or amplified locally advanced or metastatic NSCLC who have progressed on treatment with osimertinib. [Approximately 55 months post first subject randomized]

      ORR defined as the proportion of participants who have BOR of a CR or PR, as determined by BICR per RECIST 1.1.

    5. Participant-reported pulmonary core symptoms / savolitinib + osimertinib versus platinum doublet chemotherapy in participants with EGFR mutated, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC who have progressed on osimertinib. [Approximately 55 months post first subject randomized]

      TTD in pulmonary core symptoms (dyspnoea, cough, and chest pain) as measured by the NSCLC-SAQ. TTD is defined as the time from randomisation until the date of deterioration.

    6. Pharmacokinetics (PK) of savolitinib. [6 weeks after last patient dosed]

      Plasma concentrations of savolitinib and its metabolites.

    7. Disease control rate (DCR) / savolitinib + osimertinib versus platinum doublet chemotherapy in participants with EGFR mutated, MET-overexpressed and/or amplified locally advanced or metastatic NSCLC who have progressed on treatment with osimertinib. [Approximately 55 months post first subject randomized]

      DCR defined as the proportion of participants who have BOR of a CR, PR, or stable disease, as determined by BICR per RECIST 1.1.

    8. Time to discontinuation of treatment (TDT) or death / savolitinib + osimertinib vs platinum doublet chemotherapy in participants with EGFR mutated, MET-overexpressed and/or amplified locally advanced or metastatic NSCLC who have progressed on osimertinib [Approximately 55 months post first subject randomized]

      TDT or death is defined as the time from date of randomisation to the earlier of the date of study intervention discontinuation or death.

    9. Tumor shrinkage / savolitinib + osimertinib versus platinum doublet chemotherapy in participants with EGFR mutated, MET-overexpressed and/or amplified locally advanced or metastatic NSCLC who have progressed on treatment with osimertinib. [Approximately 55 months post first subject randomized]

      Tumour shrinkage defined as percentage change in tumour size in accordance with RECIST 1.1.

    10. Duration of response (DoR) / savolitinib + osimertinib versus platinum doublet chemotherapy in participants with EGFR mutated, MET-overexpressed and/or amplified locally advanced or metastatic NSCLC who have progressed on treatment with osimertinib. [Approximately 55 months post first subject randomized]

      DoR defined as the time from the date of first documented response until date of documented progression per RECIST 1.1 as assessed by BICR, or death in the absence of disease progression.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 130 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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 (≥ 20 years of age in Japan) 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:

    • 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 with the exception of alopecia, haemoglobin ≥ 9.0 g/dL, and Grade 2 prior platinum-therapy related neuropathy.

    • 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site Orange City Florida United States 32763
    2 Research Site Evergreen Park Illinois United States 60805
    3 Research Site Boston Massachusetts United States 02114
    4 Research Site New Brunswick New Jersey United States 08903
    5 Research Site Canton Ohio United States 44718
    6 Research Site Berazategui Argentina B1884BBF
    7 Research Site Caba Argentina C1019ABS
    8 Research Site Ciudad Autonoma De Buenos Aire Argentina C1125ABD
    9 Research Site Cordoba Argentina X5004APD
    10 Research Site Florida Argentina B1602DQD
    11 Research Site La Rioja Argentina F5300COE
    12 Research Site Rosario Argentina 2000
    13 Research Site Rosario Argentina 2123
    14 Research Site San Miguel de Tucumán Argentina 4000
    15 Research Site Viedma Argentina R8500ACE
    16 Research Site Fremantle Australia 6160
    17 Research Site Liverpool Australia 2170
    18 Research Site Waratah NSW Australia 2298
    19 Research Site Salzburg Austria 5020
    20 Research Site Edegem Belgium B-2650
    21 Research Site Gent Belgium 9000
    22 Research Site Roeselare Belgium 8800
    23 Research Site Sint-Niklaas Belgium 9100
    24 Research Site Porto Alegre Brazil 90035-903
    25 Research Site Montreal Quebec Canada H3T 1M5
    26 Research Site Changsha China 410013
    27 Research Site Changsha China 41003
    28 Research Site Hankou,Wuhan China 430022
    29 Research Site Zhengzhou China 450008
    30 Research Site Angers France 49933
    31 Research Site Bobigny France 93000
    32 Research Site Brest France 29200
    33 Research Site Creteil France 94010
    34 Research Site Dijon France 21079
    35 Research Site Marseille France 13915
    36 Research Site Paris France 75005
    37 Research Site Paris France 75018
    38 Research Site Poitiers France 86021
    39 Research Site Rennes Cedex 9 France 35033
    40 Research Site Rouen France 76000
    41 Research Site Saint-Herblain France 44800
    42 Research Site Avellino Italy 83100
    43 Research Site Aviano Italy 33081
    44 Research Site Catania Italy 95123
    45 Research Site Meldola Italy 47014
    46 Research Site Milan Italy 20141
    47 Research Site Monserrato Italy 09042
    48 Research Site Orbassano Italy 10043
    49 Research Site Padova Italy 35128
    50 Research Site Peschiera Del Garda Italy 37019
    51 Research Site Roma Italy 00144
    52 Research Site Roma Italy 00152
    53 Research Site Treviso Italy 31100
    54 Research Site Bunkyo-ku Japan 113-8603
    55 Research Site Hirosaki-shi Japan 036-8563
    56 Research Site Hiroshima-shi Japan 730-8518
    57 Research Site Iwakuni-shi Japan 740-8510
    58 Research Site Kobe-shi Japan 650-0017
    59 Research Site Kumamoto Japan 860-8556
    60 Research Site Kurume-shi Japan 830-0011
    61 Research Site Nagasaki-shi Japan 852-8501
    62 Research Site Okayama-shi Japan 700-8558
    63 Research Site Osaka-shi Japan 534-0021
    64 Research Site Osakasayama-shi Japan 589-8511
    65 Research Site Sakai-shi Japan 591-8555
    66 Research Site Sapporo-shi Japan 003-0804
    67 Research Site Sapporo-shi Japan 060-8638
    68 Research Site Sendai-shi Japan 980-0873
    69 Research Site Sunto-gun Japan 411-8777
    70 Research Site Utsunomiya-shi Japan 320-0834
    71 Research Site Wakayama-shi Japan 641-8510
    72 Research Site Yokohama-shi Japan 241-8515
    73 Research Site Bialystok Poland 15-003
    74 Research Site Olsztyn Poland 10-357
    75 Research Site Majadahonda Spain 28222
    76 Research Site Málaga Spain 29010
    77 Research Site Sabadell Spain 08208
    78 Research Site Izmir Turkey 35100
    79 Research Site Liverpool United Kingdom L7 3EW

    Sponsors and Collaborators

    • AstraZeneca

    Investigators

    • Principal Investigator: Shun Lu, Prof,MD,PhD,, Shanghai Chest Hospital, Shanghai JiaoTong University, #241 Huai Hai Road (west), Shanghai, China.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT05261399
    Other Study ID Numbers:
    • D5087C00001
    • 2021-006374-24
    First Posted:
    Mar 2, 2022
    Last Update Posted:
    Jul 21, 2022
    Last Verified:
    Jul 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by AstraZeneca
    Savolitinib
    Osimertinib
    EGFR
    Amplified
    Metastatic
    MET Driven
    carcinoma
    NSCLC
    overexpressed
    Additional relevant MeSH terms:
    Carcinoma, Non-Small-Cell Lung
    Carboplatin
    Pemetrexed
    Osimertinib

    Study Results

    No Results Posted as of Jul 21, 2022