A Phase II Study of HMPL-504 in Lung Sarcomatoid Carcinoma and Other Non-small Cell Lung Cancer

A Phase II, Open-label Study to Evaluate the Efficacy and Safety of HMPL-504 in Locally Advanced/Metastatic MET-Mutation-Positive Pulmonary Sarcomatoid Carcinomas and Other Non-small Cell Lung Cancer

This is a Phase II, open-label, multicenter study of Savolitinib administered orally once per day(QD) to locally advanced/metastatic PSC patients and other NSCLC patients with MET Exon 14 mutation. The targeted population is the patients with MET Exon 14 mutation who have failed prior systemic therapy (ies), or are unwilling or can not tolerate to receive chemotherapy. Pathological diagnosis will be confirmed retrospectively by the central pathological laboratory.

Study Overview

• Status: Active, not recruiting
• Conditions: Lung Sarcomatoid Carcinoma
• Intervention / Treatment: Drug: Savolitinib

Detailed Description

Savolitinib will be administrated 600mg or 400mg once per day (QD). The treatment will be discontinued for the patients who experience disease progression, death or experience unacceptable toxicity, whichever occurs first. A cycle of study treatment will be defined as 21 days of continuous dosing.

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Beijing Cancer Hopspital
  • Shanghai
    • Shanghai, Shanghai, China, 210000
      • Shanghai Chest Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 1.Fully understood the study and voluntarily signed Informed Consent Form
• 2.Age > 18 years
• 3.Histologically or cytologically documented locally advanced or Metastatic pulmonary sarcomatoid carcinoma (PSC) patients and other Non-small cell lung cancer（NSCLC） with MET Exon 14 mutation who have failed piror systemic therapy(ies), or are unwilling or unable to receive chemotherapy
• 4.Patient should have measurable disease per RECIST1.1
• 5.ECOG performance status of 0, or 1
• 6.Expected survival > 12 weeks

Exclusion Criteria:

• 1.Co-existing malignancy or malignancies diagnosed within the last 3 years other than lung cancer with the exception of adequately treated skin basal cell carcinoma or cervical cancer in situ.
• 2.Any anti-cancer therapy, including chemotherapy, hormonal therapy, biologic therapy or radiotherapy within 3weeks prior to initiation of study treatment, or received TKI (for ex. EGFR-TKI) treatment within 2 week prior to initiation of study treatment
• 3.Palliative radiation to bone metastases within 2 weeks prior to the initiation of study treatment
• 4.Herbal therapy within 1 week prior to the initiation of study treatment
• 5. has EGFR, ALK or ROS 1 positive mutation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Savolitinib; Pulmonary Sarcomatoid Carcinomas	Drug: Savolitinib; Enrolled patients will be treated with Savolitinib 600mg or 400mg once per day(QD), till disease progression, death or unacceptable toxicity, whichever comes first. A cycle of study treatment will be defined as 21 days of continuous dosing.; Other Names: hmpl-504

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess objective response rate (ORR)	ORR is defined as the proportion of patients with complete response or partial response. The confirmation of response for patients who has PR or CR at first time should be performed by at least 4 weeks and in this study, it could be performed by the scheduled tumor assessment 6 weeks later	1year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival(PFS)	PFS is defined as the Progression free surviva of patients with complete response or partial response or stable disease. In the case of SD, measurements must have met the SD criteria at least once after study entry at a minimum interval of 6 weeks.	1year
Safety Assessment Parameter	The safety will be assessed using the following safety outcome measures: incidence of adverse events, physical examinations,vital signs and laboratory tests (including hematology, clinical chemistry, urine tests and other indicators)12-ECG parameters and echocardiogram.	1year

Collaborators and Investigators

• Sponsor: Hutchison Medipharma Limited

Publications and helpful links

General Publications

• Yu Y, Ren Y, Fang J, Cao L, Liang Z, Guo Q, Han S, Ji Z, Wang Y, Sun Y, Chen Y, Li X, Xu H, Zhou J, Jiang L, Cheng Y, Han Z, Shi J, Chen G, Ma R, Fan Y, Sun S, Jiao L, Jia X, Wang L, Lu P, Xu Q, Luo X, Su W, Lu S. Circulating tumour DNA biomarkers in savolitinib-treated patients with non-small cell lung cancer harbouring MET exon 14 skipping alterations: a post hoc analysis of a pivotal phase 2 study. Ther Adv Med Oncol. 2022 Oct 31;14:17588359221133546. doi: 10.1177/17588359221133546. eCollection 2022.
• Paik PK, Pfeiffer BM, Vioix H, Garcia A, Postma MJ. Matching-Adjusted Indirect Comparison (MAIC) of Tepotinib with Other MET Inhibitors for the Treatment of Advanced NSCLC with MET Exon 14 Skipping Mutations. Adv Ther. 2022 Jul;39(7):3159-3179. doi: 10.1007/s12325-022-02163-9. Epub 2022 May 11.
• Lu S, Fang J, Li X, Cao L, Zhou J, Guo Q, Liang Z, Cheng Y, Jiang L, Yang N, Han Z, Shi J, Chen Y, Xu H, Zhang H, Chen G, Ma R, Sun S, Fan Y, Li J, Luo X, Wang L, Ren Y, Su W. Once-daily savolitinib in Chinese patients with pulmonary sarcomatoid carcinomas and other non-small-cell lung cancers harbouring MET exon 14 skipping alterations: a multicentre, single-arm, open-label, phase 2 study. Lancet Respir Med. 2021 Oct;9(10):1154-1164. doi: 10.1016/S2213-2600(21)00084-9. Epub 2021 Jun 21.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2016
• Primary Completion (Anticipated): December 30, 2021
• Study Completion (Anticipated): December 30, 2021

Study Registration Dates

• First Submitted: August 29, 2016
• First Submitted That Met QC Criteria: September 7, 2016
• First Posted (Estimate): September 13, 2016

Study Record Updates

• Last Update Posted (Actual): November 30, 2021
• Last Update Submitted That Met QC Criteria: November 29, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma
• Other Study ID Numbers: 2016-504-00CH1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No