Sym015 (Anti-MET) in Patients With Advanced Solid Tumor Malignancies

NCT02648724 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: Sym015-012016-003912-11
• Study Type: interventional
• Target: 57
• Locations: 6 countries
• Sites: 27

Brief Summary

This is the first study to test Sym015 in humans. The primary purpose of this study is to see if Sym015 is safe and effective for patients with advanced solid tumor malignancies without available therapeutic options.

Conditions

Oncology; MET Gene Amplification; NSCLC; MET Gene Mutation; Non Small Cell Lung Cancer

Keywords

Advanced Solid Tumor Malignancies; MET Gene Amplification; MET Amplification; Wild-type; NSCLC; METex14del; Non-Small Cell Lung Carcinoma

Outcome Measures

Primary Outcomes (2)

• Part 1: Occurrence of DLTs During Cycle 1 of Sym015 Administration

  The primary objective of Part 1 was to assess the safety and tolerability of Sym015 on a Q2W schedule. This was assessed by evaluating the occurrence of dose-limiting toxicities (DLTs) during Cycle 1 of Sym015 administration. Q2W = every second week.

  Cycle 1, the initial 28-day period of Q2W dosing

• Part 2: Documented, Confirmed Objective Response (OR)

  The primary objective of Part 2 was to evaluate the antitumor activity of Sym015 when administered at the Q2W RP2D to patients in the different cohorts. Documented OR was defined as partial response \[PR\] or complete response \[CR\]) as assessed by CT or MRI using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 at any time during trial participation by Investigator assessment. PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; CR = Disappearance of all non-target lesions and normalisation of tumour marker level. All lymph nodes must be non-pathological in size (\<10 mm short axis). Q2W = every second week. RP2D = recommended phase 2 dose.

  24 months

Secondary Outcomes (17)

• Part 1: Determine a Q2W RP2D of Sym015.

  12 Months

• Immunogenicity of Sym015: Part 1.

  Cycle 1: Day (D) 1, Cycle 3, 5, 7: D1 (+-2), End of treatment: At or by D10, Follow-up: 1 month after last dose of study treatment (30+7D)

• Immunogenicity of Sym015: Part 2.

  Cycle 1: Day (D) 1, Cycle 2, 3, 5, 7: D1 (+-2), End of treatment: At or by D10, Follow-up: 1 month after last dose of study treatment (30+7D)

• Part 1: Area Under the Concentration-time Curve in a Dosing Interval (AUC) Following 1st Dose

  From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.

• Part 2: Area Under the Concentration-time Curve in a Dosing Interval (AUC)

  From time zero to 48 hours after dosing. Samples taken pre-dosing and at 1, 2, 4, 8, 24 and 48 hours after end of infusion.

Study Arms (7)

Part 1: 6 mg/kg

EXPERIMENTAL

Sym015 was tested in four dose titration cohorts. Patients in this cohort received 6 mg/kg. A substitute or an additional dose level could potentially be evaluated.

Drug: Sym015

Part 1: 12 mg/kg

EXPERIMENTAL

Sym015 was tested in four dose titration cohorts. Patients in this cohort received 12 mg/kg. A substitute or an additional dose level could potentially be evaluated.

Drug: Sym015

Part 1: 18 mg/kg

EXPERIMENTAL

Sym015 was tested in four dose titration cohorts. Patients in this cohort received 18 mg/kg. A substitute or an additional dose level could potentially be evaluated.

Drug: Sym015

Part 1: 24 mg/kg

EXPERIMENTAL

Sym015 was tested in four dose titration cohorts. Patients in this cohort received 24 mg/kg. A substitute or an additional dose level could potentially be evaluated.

Drug: Sym015

Part 2: Basket Cohort

EXPERIMENTAL

Patients with KRAS WT advanced solid tumor malignancies with MET-amplification were to receive Sym015 at the RP2D. Included in this group was a subset of patients who have received prior therapy with a MET-targeting TKI.

Drug: Sym015

Part 2: NSCLC MET-Amplified Cohort

EXPERIMENTAL

Patients with advanced NSCLC with MET-amplification were to receive Sym015 at the RP2D. Patients may have received prior therapy with MET-targeting and/or EGFR-targeting agents.

Drug: Sym015

Part 2: NSCLC METex14del Cohort

EXPERIMENTAL

Patients with advanced NSCLC with METex14del were to receive Sym015 at the RP2D. Tumors need not be MET-amplified, and patients may have received prior therapy with MET-targeting and/or EGFR-targeting agents. mutation.

Drug: Sym015

Interventions

Sym015 DRUG

Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.

Also known as: Anti-MET

Part 1: 12 mg/kg; Part 1: 18 mg/kg; Part 1: 24 mg/kg; Part 1: 6 mg/kg; Part 2: Basket Cohort; Part 2: NSCLC MET-Amplified Cohort; Part 2: NSCLC METex14del Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
• Life expectancy \>3 months assessed during Screening.
• Documented (histologically- or cytologically-proven) solid tumor malignancy that is locally advanced or metastatic, and that is refractory to standard therapy or for which no standard therapy is available or accessible.
• If female and of childbearing potential: a negative pregnancy test.
• Male or female: either not of childbearing potential or agreeing to use a medically effective method of contraception as per institutional standards during the trial and for 4 months after the last dose of trial drug.
• Part 1 ONLY: Tumor documented to be KRAS WT by local assessment.
• Part 2 ONLY:
• Measurable disease according to RECIST v1.1 that has been confirmed by computed tomography (CT) or magnetic resonance imaging (MRI) within 4 weeks prior to Cycle 1/Day 1 (C1/D1).
• Basket Cohort ONLY:
• Tumor documented to be KRAS WT by local assessment according to institutional standards. If KRAS WT is not previously documented and if archival tissue is not available for pretrial assessment, patient must be willing to undergo a tumor biopsy to confirm eligibility.
• Confirmed MET-amplification by local assessment.
• No prior therapy with MET-targeting agents (except a subset of patients having received prior therapy with a MET-targeting TKI).
• Willingness to undergo a pre- and post-dosing biopsy (maximum of 2 biopsies) from primary or metastatic tumor site(s) considered safely accessible for biopsy
• NSCLC MET-Amplified Cohort ONLY:
• Documented NSCLC meeting disease criteria as defined per protocol.

You may not qualify if:

• Any antineoplastic agent for the primary malignancy (standard or investigational) without delayed toxicity within 4 weeks or 5 plasma half-lives, whichever is shortest, prior to C1/D1, except nitrosoureas and mitomycin C within 6 weeks prior to C1/D1.
• Immunosuppressive or systemic hormonal therapy within 2 weeks prior to C1/D1, with exceptions.
• Use of hematopoietic growth factors within 2 weeks prior to C1/D1.
• Active second malignancy or history of another malignancy within the last 3 years, with exceptions.
• Central nervous system (CNS) malignancy including primary malignancies of the CNS and known, untreated CNS or leptomeningeal metastases, or spinal cord compression; patients with any of these not controlled by prior surgery or radiotherapy, or symptoms suggesting CNS involvement for which treatment is required.
• Inadequate recovery from an acute toxicity associated with any prior antineoplastic therapy.
• Major surgical procedure within 4 weeks prior to C1/D1 or inadequate recovery from any prior surgical procedure.
• Active thrombosis, or a history of deep vein thrombosis or pulmonary embolism, within 1 month prior to C1/D1, unless adequately treated and stable.
• Active uncontrolled bleeding or a known bleeding diathesis.
• Significant cardiovascular disease or condition.
• Abnormal hematologic, renal or hepatic function.
• Part 2 ONLY:
• Radiotherapy against target lesions within 4 weeks prior to C1/D1, unless there is documented progression of the lesion following the radiotherapy.
• Basket Cohort ONLY:
• Prior therapy with MET-inhibiting agents (exceptions will be a subset of patients that will be entered to the Basket Cohort after having received prior therapy with a MET-targeting TKI).

Sponsors & Collaborators

• Symphogen A/S: lead

Study Sites (27)

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Indiana University Health Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute/D -1251

Boston, Massachusetts, 02215, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

The University of Texas M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

South Texas Accelerated Research Therapeutics, LLC

San Antonio, Texas, 78229, United States

Location

Rigshospitalet

Copenhagen, 2100, Denmark

Location

Queen Mary Hospital

Hong Kong, Hong Kong

Location

CHA Bundang Medical Center, CHA University

Seongnam-si, Gyeonggi-do, 13496, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Gangnam Severance Hospital, Yonsei University Health System

Seoul, 06273, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Korea University Guro Hospital

Seoul, 08308, South Korea

Location

Hospital Universitario Quiron Dexeus

Barcelona, Barcelona/Cataluna, 08028, Spain

Location

Hospital Universitario Vall d'Hebron

Barcelona, Barcelona/Cataluna, 08035, Spain

Location

Hospital Clinic de Barcelona

Barcelona, Barcelona/Cataluna, 08036, Spain

Location

Centro Oncologico MD Anderson

Madrid, 28033, Spain

Location

China Medical University Hospital

Taichung, 40447, Taiwan

Location

Taichung Veterans General Hospital

Taichung, 40705, Taiwan

Location

National Cheng Kung University Hospital

Tainan, 70403, Taiwan

Location

Taipei Medical University Hospital

Taipei, 11031, Taiwan

Location

Tri-Service General Hospital

Taipei, 11490, Taiwan

Location

Related Publications (1)

• Grandal MM, Havrylov S, Poulsen TT, Koefoed K, Dahlman A, Galler GR, Conrotto P, Collins S, Eriksen KW, Kaufman D, Woude GFV, Jacobsen HJ, Horak ID, Kragh M, Lantto J, Bouquin T, Park M, Pedersen MW. Simultaneous Targeting of Two Distinct Epitopes on MET Effectively Inhibits MET- and HGF-Driven Tumor Growth by Multiple Mechanisms. Mol Cancer Ther. 2017 Dec;16(12):2780-2791. doi: 10.1158/1535-7163.MCT-17-0374. Epub 2017 Aug 11.

  PMID: 28802255 DERIVED

MeSH Terms

Conditions

Neoplasms; Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Medical Director
• Organization: Symphogen AS

info@symphogen.com

0045 45265050

Study Officials

• Amita Patnaik, MD, FRCP(C)

  South Texas Accelerated Research Therapeutics, LLC

  PRINCIPAL INVESTIGATOR

• David Ross Camidge, MD, PhD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Arms 1-4 comprises part 1 (dose-escalation), which is an as evaluation of 4 different dose levels (DL), 6, 12, 18, and 24 mg/kg. DL data from part 1 is presented as merged in the other sections. This is due to that there were no dose level toxicities reported during the study. Arms 5-7 comprises part 2 (dose-expansion).

Study Record Dates

• First Submitted: January 4, 2016
• First Posted: January 7, 2016
• Study Start: March 1, 2016
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2020
• Last Updated: June 22, 2022
• Results First Posted: June 22, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (10); ES (4); DK (1); HK (1); KR (6); TW (5)