Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02648724
Recruitment Status : Recruiting
First Posted : January 7, 2016
Last Update Posted : May 30, 2019
Sponsor:
Information provided by (Responsible Party):
Symphogen A/S

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.

Condition or disease Intervention/treatment Phase
Oncology MET Gene Amplification NSCLC MET Gene Mutation Non Small Cell Lung Cancer Drug: Sym015 Phase 1 Phase 2

Detailed Description:

In the first part of the study (Part 1, dose-escalation), Sym015 will be evaluated for safety and tolerability. Additionally, the recommended Phase 2 dose (RP2D) will be determined. Sym015 will be given at different dose levels on an every second week (Q2W) dosing schedule. Each patient will be given one fixed dose level.

In the second part of the study (Part 2, dose-expansion), dosing will be at the RP2D on a Q2W dosing schedule. Three cohorts will be included:

  • Basket Cohort: Patients with KRAS wild-type (WT) advanced solid tumor malignancies with MET-amplification and without therapeutic options. Patients must have no prior therapy with MET-targeting agents, except a subset of patients having received prior therapy with a MET-targeting tyrosine kinase inhibitor (TKI). As of December 2018, accrual to this cohort is suspended.
  • Non-Small Cell Lung Carcinoma (NSCLC) MET-Amplified Cohort: Patients with advanced NSCLC with MET-amplification, and without available therapeutic options. Patients may have received prior therapy with MET-targeting and/or epidermal growth factor receptor (EGFR)-targeting agents.
  • NSCLC with MET exon 14 skipping alteration (METex14del) Cohort: Patients with advanced NSCLC METex14del, and without therapeutic options. Tumors need not be MET-amplified, and patients may have received prior therapy with MET-targeting and/or EGFR-targeting agents.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 72 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Multicenter Phase 1a/2a Trial Investigating the Safety, Tolerability and Antitumor Activity of Multiple Doses of Sym015, a Monoclonal Antibody Mixture Targeting MET, in Patients With Advanced Solid Tumor Malignancies
Actual Study Start Date : March 2016
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : September 2020

Arm Intervention/treatment
Experimental: Part 1: Dose-Escalation
Sym015 will be tested in four dose titration cohorts. A substitute or an additional dose level could potentially be evaluated.
Drug: Sym015
Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
Other Name: Anti-MET

Experimental: Part 2: Basket Cohort
Patients with KRAS WT advanced solid tumor malignancies with MET-amplification will receive Sym015 at the RP2D. Included in this group will be a subset of patients who have received prior therapy with a MET-targeting TKI.
Drug: Sym015
Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
Other Name: Anti-MET

Experimental: Part 2: NSCLC MET-Amplified Cohort
Patients with advanced NSCLC with MET-amplification will receive Sym015 at the RP2D. Patients may have received prior therapy with MET-targeting and/or EGFR-targeting agents.
Drug: Sym015
Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
Other Name: Anti-MET

Experimental: Part 2: NSCLC METex14del Cohort
Patients with advanced NSCLC with METex14del will 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
Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
Other Name: Anti-MET




Primary Outcome Measures :
  1. Part 1: Assess the safety and tolerability of Sym015 on a Q2W schedule. [ Time Frame: 12 months ]
    Assess the occurrence of dose-limiting toxicities (DLTs) during Cycle 1 of Sym015 administration.

  2. Part 2: Evaluate the antitumor activity of Sym015 when administered at the Q2W RP2D. [ Time Frame: 24 months ]
    Documented objective response (OR) (defined as partial response [PR] or complete response [CR]) in the Basket Cohort, assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 at any time during trial participation by Investigator assessment.


Secondary Outcome Measures :
  1. Part 1: Determine a Q2W RP2D of Sym015. [ Time Frame: 12 Months ]
    Determination based on an evaluation of the patient data for DLTs from Part 1.

  2. Parts 1 and 2: Evaluate the immunogenicity of Sym015. [ Time Frame: 36 Months ]
    Serum sampling to assess the potential for anti-drug antibody (ADA) formation. For Part 2, this applies to both the Basket Cohort and the NSCLC Cohort.

  3. Parts 1 and 2: Evaluate potential biomarkers of Sym015 action, and estimate, if feasible, the magnitude of biological activity. [ Time Frame: 36 Months ]
    Potential biomarkers of interest include genes, gene transcripts and proteins of the receptor tyrosine kinases (RTKs) and molecules of the MET signaling pathway. For Part 2, this applies to both the Basket Cohort and the NSCLC Cohort.

  4. Parts 1 and 2: Area under the concentration-time curve in a dosing interval (AUC) [ Time Frame: 36 Months ]
    Will be estimated using non-compartmental methods and actual time points. For Part 2, this applies to both the Basket Cohort and the NSCLC Cohort.

  5. Parts 1 and 2: Maximum concentration (Cmax) [ Time Frame: 36 months ]
    Will be derived from observed data. For Part 2, this applies to both the Basket Cohort and the NSCLC Cohort.

  6. Parts 1 and 2: Time to reach maximum concentration (Tmax) [ Time Frame: 36 Months ]
    Will be derived from observed data. For Part 2, this applies to both the Basket Cohort and the NSCLC Cohort.

  7. Parts 1 and 2: Trough concentration (Ctrough) [ Time Frame: 36 Months ]
    Will be derived from observed data. For Part 2, this applies to both the Basket Cohort and the NSCLC Cohort.

  8. Parts 1 and 2: Elimination half-life (T½) [ Time Frame: 36 Months ]
    Will be estimated using non-compartmental methods and actual time points. For Part 2, this applies to both the Basket Cohort and the NSCLC Cohort.

  9. Parts 1 and 2: Clearance (CL) [ Time Frame: 36 Months ]
    Will be estimated using non-compartmental methods and actual time points. For Part 2, this applies to both the Basket Cohort and the NSCLC Cohort.

  10. Part 2: Additional preliminary evaluation of the antitumor activity of Sym015 when administered at the Q2W RP2D in a subset of patients. [ Time Frame: 24 Months ]
    This applies to the subset of patients in the Basket Cohort who received prior therapy with a MET-targeting TKI. Documented OR (defined as PR or CR), assessed by RECIST v1.1 at any time during trial participation by Investigator assessment.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.
      • Documented MET-amplification.
      • May have received prior therapy with MET-targeting and/or EGFR-targeting agents (antibodies or TKIs).
      • Willingness to undergo a pre-dosing biopsy (mandatory unless a recent tumor biopsy is available), and potentially a biopsy at the End of Cycle 2 (EOC2) (optional), from a primary or metastatic tumor site considered safely accessible for biopsy.
    • NSCLC METex14del Cohort ONLY:

      • Documented NSCLC meeting disease criteria as defined per protocol.
      • Documented METex14del (tumors need not be MET-amplified).
      • May have received prior therapy with MET-targeting and/or EGFR-targeting agents (antibodies or TKIs).
      • Willingness to undergo a pre-dosing biopsy (mandatory unless a recent tumor biopsy is available), and potentially a biopsy at the EOC2 (optional), from a primary or metastatic tumor site considered safely accessible for biopsy.

Exclusion Criteria:

  • 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).
      • Prior therapy with antibody to hepatocyte growth factor (HGF).
    • Basket Cohort and NSCLC MET-Amplified Cohort ONLY:

      • Tumor status demonstrating MET-polysomy in the absence of MET-amplification, as specified per protocol. Patients in the NSCLC METex14del Cohort with polysomy are eligible.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02648724


Contacts
Layout table for location contacts
Contact: Helle Rudbaek +45 8838 2600 heru@symphogen.com

Locations
Layout table for location information
United States, Colorado
University of Colorado Cancer Center Recruiting
Aurora, Colorado, United States, 80045
Contact: Paula Fisk       paula.fisk@ucdenver.edu   
Principal Investigator: David Ross Camidge, MD, PhD         
United States, Illinois
University of Chicago Medical Center Recruiting
Chicago, Illinois, United States, 60637
Contact: Daniel Catenacci, MD    773-702-7596    dcatenac@medicine.bsd.uchicago.edu   
Principal Investigator: Daniel Catenacci, MD         
United States, Indiana
Indiana University Health Melvin and Bren Simon Cancer Center Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Shadia Jalal, MD       sjalal@Iupui.edu   
Principal Investigator: Shadia Jalal, MD         
United States, Nevada
Comprehensive Cancer Centers of Nevada Recruiting
Las Vegas, Nevada, United States, 89169
Contact: Fadi Braiteh, MD    702-952-3400    fadi.braiteh@usoncology.com   
Principal Investigator: Fadi Braiteh, MD         
United States, Ohio
University Hospitals Cleveland Medical Center Recruiting
Cleveland, Ohio, United States, 44106
Contact: Afshin Dowlati, MD         
Principal Investigator: Afshin Dowlati, MD         
United States, Texas
University of Texas Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390
Principal Investigator: Muhammad Beg         
The University of Texas M.D. Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Filip Janku, MD, PhD    713-563-2632    fjanku@mdanderson.org   
Principal Investigator: Filip Janku, MD, PhD         
South Texas Accelerated Research Therapeutics, LLC Completed
San Antonio, Texas, United States, 78229
Denmark
Rigshospitalet Recruiting
Copenhagen, Denmark, 2100
Contact: Kristoffer Staal Rohrberg, MD, PhD    +45 3545 6353    kristoffer.staal.rohrberg@regionh.dk   
Principal Investigator: Kristoffer Staal Rohrberg, MD, PhD         
Hong Kong
Queen Mary Hospital Completed
Hong Kong, Hong Kong
Korea, Republic of
CHA Bundang Medical Center, CHA University Recruiting
Seongnam-si, Gyeonggi-do, Korea, Republic of, 13496
Contact: Yong Wha Moon, MD, PhD    +82 3 1780 3436    ymoon@cha.ac.kr   
Principal Investigator: Yong Wha Moon, MD, PhD         
Severance Hospital, Yonsei University Health System Recruiting
Seoul, Korea, Republic of, 03722
Contact: Hyun Cheol Chung, MD, PhD    +82 2 2228 8132    unchung8@yuhs.ac   
Principal Investigator: Hyun Cheol Chung, MD, PhD         
Asan Medical Center Recruiting
Seoul, Korea, Republic of, 05505
Contact: Yoon-Koo Kang, MD, PhD    +82 2 3010 3230    ykkang@amc.seoul.kr   
Principal Investigator: Yoon-Koo Kang, MD, PhD         
Gangnam Severance Hospital, Yonsei University Health System Recruiting
Seoul, Korea, Republic of, 06273
Contact: Hei-Cheul Jeung, MD, PhD    + 82 2 2019 3297    jeunghc1123@yuhs.ac   
Principal Investigator: Hei-Cheul Jeung, MD, PhD         
Samsung Medical Center Recruiting
Seoul, Korea, Republic of, 06351
Contact: Jeeyun Lee, MD, PhD    +82 2 3410 1779    jyunlee@skku.edu   
Principal Investigator: Jeeyun Lee, MD, PhD         
Korea University Guro Hospital Recruiting
Seoul, Korea, Republic of, 08308
Contact: Sang Cheul Oh, MD, PhD    +82 2 2626 3060    sachoh@korea.ac.kr   
Principal Investigator: Sang Cheul Oh, MD, PhD         
Spain
Hospital Universitario Quiron Dexeus Recruiting
Barcelona, Barcelona/Cataluna, Spain, 08028
Contact: Alejandro Martinez Bueno, MD    +34 93 546 0135    amartinez@oncorosell.com   
Principal Investigator: Alejandro Martinez Bueno, MD         
Hospital Universitario Vall d'Hebron Recruiting
Barcelona, Barcelona/Cataluna, Spain, 08035
Contact: Enriqueta Felip Font, MD       efelip@vhio.net   
Principal Investigator: Enriqueta Felip Font, MD         
Hospital Clinic de Barcelona Recruiting
Barcelona, Barcelona/Cataluna, Spain, 08036
Contact: Javier Garcia Corbacho, MD       garcia33@clinic.ub.es   
Principal Investigator: Javier Garcia Corbacho, MD         
Centro Oncologico MD Anderson Recruiting
Madrid, Spain, 28033
Contact: Maria Pilar Lopez Criado, MD    +34 91 787 8600    mplopez@mdanderson.es   
Principal Investigator: Maria Pilar Lopez Criado, MD         
Taiwan
China Medical University Hospital Recruiting
Taichung, Taiwan, 40447
Contact: Chang-Fang Chiu, MD, PhD    +886 4 2205 2121 ext 5051    d5686@mail.cmuh.org.tw   
Principal Investigator: Chang-Fang Chiu, MD, PhD         
Taichung Veterans General Hospital Recruiting
Taichung, Taiwan, 40705
Contact: Gee-Chen Chang, MD       august@vghtc.gov.tw   
Principal Investigator: Gee-Chen Chang, MD         
National Cheng Kung University Hospital Completed
Tainan, Taiwan, 70403
Taipei Medical University Hospital Recruiting
Taipei, Taiwan, 11031
Contact: Her-Shyong Shiah, MD    +886 2 2737 2181    121010@h.tmu.edu.tw   
Principal Investigator: Her-Shyong Shiah, MD         
Tri-Service General Hospital Completed
Taipei, Taiwan, 11490
Sponsors and Collaborators
Symphogen A/S
Investigators
Layout table for investigator information
Principal Investigator: Amita Patnaik, MD, FRCP(C) South Texas Accelerated Research Therapeutics, LLC
Principal Investigator: David Ross Camidge, MD, PhD University of Colorado, Denver

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Symphogen A/S
ClinicalTrials.gov Identifier: NCT02648724     History of Changes
Other Study ID Numbers: Sym015-01
2016-003912-11 ( EudraCT Number )
First Posted: January 7, 2016    Key Record Dates
Last Update Posted: May 30, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Symphogen A/S:
Advanced Solid Tumor Malignancies
MET Gene Amplification
MET Amplification
Wild-type
NSCLC
METex14del
Non-Small Cell Lung Carcinoma
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasms
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs