OncologyPhase 1/2NCT02648724
Sym015 (Anti-MET) in Patients With Advanced Solid Tumor Malignancies
A Phase 1/2 study testing Sym015 in people with Oncology and MET Gene Amplification, run by Symphogen A/S at 27 sites in 6 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Oncology, MET Gene Amplification, NSCLC
- What is being tested?
- Sym015
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 57 participants
- Where
- 27 sitesin 6 countries
- Study dates
- Mar 2016to Dec 2020
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 23Show fewer
- 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.
Who cannot join
- 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.
Show all 18Show fewer
- 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.
Trial locations and contacts
27 sites in 6 countries.
27 sites in 6 countries
United States10 sites
University of Colorado Cancer Center
Aurora, Colorado, 80045
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana Farber Cancer Institute/D -1251
Boston, Massachusetts, 02215
University of Chicago Medical Center
Chicago, Illinois, 60637
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
The University of Texas M.D. Anderson Cancer Center
Houston, Texas, 77030
Indiana University Health Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, 89169
South Texas Accelerated Research Therapeutics, LLC
San Antonio, Texas, 78229
South Korea6 sites
CHA Bundang Medical Center, CHA University
Seongnam-si, Gyeonggi-do, 13496
Severance Hospital, Yonsei University Health System
Seoul, 03722
Asan Medical Center
Seoul, 05505
Gangnam Severance Hospital, Yonsei University Health System
Seoul, 06273
Samsung Medical Center
Seoul, 06351
Korea University Guro Hospital
Seoul, 08308
Taiwan5 sites
China Medical University Hospital
Taichung, 40447
Taichung Veterans General Hospital
Taichung, 40705
National Cheng Kung University Hospital
Tainan, 70403
Taipei Medical University Hospital
Taipei, 11031
Tri-Service General Hospital
Taipei, 11490
Spain4 sites
Hospital Universitario Quiron Dexeus
Barcelona, Barcelona/Cataluna, 08028
Hospital Universitario Vall d'Hebron
Barcelona, Barcelona/Cataluna, 08035
Hospital Clinic de Barcelona
Barcelona, Barcelona/Cataluna, 08036
Centro Oncologico MD Anderson
Madrid, 28033
About this study
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
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.
Read the detailed description
In the first part of the study (Part 1, dose-escalation), Sym015 was evaluated for safety and tolerability. Additionally, the recommended Phase 2 dose (RP2D) was to be determined. Sym015 was given at different dose levels on an every second week (Q2W) dosing schedule. Each patient was given one single weight based dose level.
In the second part of the study (Part 2, dose-expansion), dosing was to be at the RP2D on a Q2W dosing schedule. Three cohorts were 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 was 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.
- Being tested
- Sym015
- Keywords
- Advanced Solid Tumor Malignancies, MET Gene Amplification, MET Amplification, Wild-type, NSCLC, METex14del, Non-Small Cell Lung Carcinoma
- Medical subject headings
- Neoplasms, Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sym015Drug
Also called Anti-MET
Sym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Sym015 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 24 months
Secondary outcomes (17)
Part 1: Determine a Q2W RP2D of Sym015.
Determination based on an evaluation of the patient data for DLTs from Part 1. Q2W = every second week. RP2D = recommended phase 2 dose.
Measured: 12 Months
Immunogenicity of Sym015: Part 1.
Serum sampling was done to assess the potential for anti-drug antibody (ADA) formation.
Measured: 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.
Serum sampling was done to assess the potential for anti-drug antibody (ADA) formation.
Measured: 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
Estimated using non-compartmental methods and actual time points following the first dose of Sym015.
Measured: 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)
Estimated using non-compartmental methods and actual time points following the first dose of Sym015 for the whole basket cohort.
Measured: 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 1: Cmax
Maximum serum concentration was derived from observed data.
Measured: 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: Cmax
Maximum serum concentration was derived from observed data following the first dose of Sym015 for the full basket cohort.
Measured: 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 1: Time to Reach Maximum Concentration (Tmax)
Time to reach maximum concentration (Tmax) was derived from observed data.
Measured: 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: Time to Reach Maximum Concentration (Tmax)
Time to reach maximum concentration (Tmax) was derived from observed data following the first dose of Sym015 for the full basket cohort.
Measured: 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 1: Trough Concentration (Ctrough)
Ctrough was derived from observed data.
Measured: 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: Trough Concentration (Ctrough)
Ctrough was derived from observed data following the first dose of Sym015 for the whole basket cohort.
Measured: 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 1: Elimination Half-life (T½)
Estimated using non-compartmental methods and actual time points.
Measured: 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: Elimination Half-life (T½)
Estimated using non-compartmental methods and actual time points following the first dose of Sym015 for the whole basket cohort.
Measured: 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 1: Clearance (CL)
Estimated using non-compartmental methods and actual time points.
Measured: 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: Clearance (CL)
Estimated using non-compartmental methods and actual time points following the first dose of Sym015 for the whole basket cohort.
Measured: 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: Additional Preliminary Evaluation of the Antitumor Activity of Sym015 When Administered at the Q2W RP2D in a Subset of Patients. Assessed by OR.
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.
Objective Response (OR) is presented. 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).
Measured: 24 Months
Part 2: Additional Preliminary Evaluation of the Antitumor Activity of Sym015 When Administered at the Q2W RP2D in a Subset of Patients. Assessed by DCR.
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.
Disease control rate (DCR) is presented. The DCR was defined as the percentage of patients who had BOR of confirmed CR or confirmed PR or SD (including unconfirmed CR/PR, provided 6 weeks minimum criteria for SD duration was met).
BOR = Best Overall Response. CR = Complete Response. PR = Partial Response. SD = Stable Disease.
Measured: 24 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jan 2016 (estimated)
- Study startMar 2016
- Primary completionDec 2020
- Study completionDec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for OncologyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- 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).
- Masking
- None (open label)
- Enrolment
- 57 participants (actual)
Sponsor and investigators
- Lead sponsor
- Symphogen A/S
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Amita Patnaik, MD, FRCP(C), Principal investigator, South Texas Accelerated Research Therapeutics, LLCDavid Ross Camidge, MD, PhD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02648724
- Sponsor's protocol ID
- Sym015-01
- Other IDs
- 2016-003912-11, 2016
- Status last verified
- Apr 2022
- First submitted
- 4 Jan 2016
- Last updated
- 22 Jun 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 28802255
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02648724
- Acronym / sponsor ID
- Sym015-01
- Keywords
- Advanced Solid Tumor Malignancies, MET Gene Amplification, MET Amplification, Wild-type, NSCLC, METex14del, Non-Small Cell Lung Carcinoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 57 participants (actual)
- Lead sponsor
- Symphogen A/SIndustry (pharma, biotech, devices)
- Study start
- Mar 2016 (actual)
- Primary completion
- Dec 2020 (actual)
- Study completion
- Dec 2020 (actual)
- First posted
- 7 Jan 2016 (estimated)
- Results
- Posted 22 Jun 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
In the first part of the study (Part 1, dose-escalation), Sym015 was evaluated for safety and tolerability. Additionally, the recommended Phase 2 dose (RP2D) was to be determined. Sym015 was given at different dose levels on an every second week (Q2W) dosing schedule. Each patient was given one single weight based dose level.
In the second part of the study (Part 2, dose-expansion), dosing was to be at the RP2D on a Q2W dosing schedule. Three cohorts were 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 was 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 7
- Model description
- 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).
| Arm | Type | Receives |
|---|---|---|
| Part 1: 6 mg/kg | Experimental | Drug: Sym015Sym015 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. |
| Part 1: 12 mg/kg | Experimental | Drug: Sym015Sym015 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. |
| Part 1: 18 mg/kg | Experimental | Drug: Sym015Sym015 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. |
| Part 1: 24 mg/kg | Experimental | Drug: Sym015Sym015 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. |
| Part 2: Basket Cohort | Experimental | Drug: Sym015Patients 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. |
| Part 2: NSCLC MET-Amplified Cohort | Experimental | Drug: Sym015Patients 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. |
| Part 2: NSCLC METex14del Cohort | Experimental | Drug: Sym015Patients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- 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.
Key exclusion criteria (18 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sym015Also: Anti-METSym015 is a mixture of two monoclonal antibodies which specifically bind to non-overlapping epitopes in the extracellular domain of MET. | Drug | 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 |
Primary outcome
Part 1: Occurrence of DLTs During Cycle 1 of Sym015 Administration
Time frame: Cycle 1, the initial 28-day period of Q2W dosing
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.
Part 2: Documented, Confirmed Objective Response (OR)
Time frame: 24 months
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.
17 secondary outcomes
Part 1: Determine a Q2W RP2D of Sym015.
Time frame: 12 Months
Immunogenicity of Sym015: Part 1.
Time frame: 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.
Time frame: 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
Time frame: 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)
Time frame: 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 1: Cmax
Time frame: 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: Cmax
Time frame: 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 1: Time to Reach Maximum Concentration (Tmax)
Time frame: 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: Time to Reach Maximum Concentration (Tmax)
Time frame: 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 1: Trough Concentration (Ctrough)
Time frame: 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: Trough Concentration (Ctrough)
Time frame: 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 1: Elimination Half-life (T½)
Time frame: 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: Elimination Half-life (T½)
Time frame: 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 1: Clearance (CL)
Time frame: 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: Clearance (CL)
Time frame: 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: Additional Preliminary Evaluation of the Antitumor Activity of Sym015 When Administered at the Q2W RP2D in a Subset of Patients. Assessed by OR.
Time frame: 24 Months
Part 2: Additional Preliminary Evaluation of the Antitumor Activity of Sym015 When Administered at the Q2W RP2D in a Subset of Patients. Assessed by DCR.
Time frame: 24 Months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28802255Grandal 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Amita Patnaik, MD, FRCP(C) principal investigator
South Texas Accelerated Research Therapeutics, LLC
David Ross Camidge, MD, PhD principal investigator
University of Colorado, Denver
27 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Sym015 in people with Oncology and MET Gene Amplification, run by Symphogen A/S at 27 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 27 sites in United States, South Korea, Taiwan, Spain, Denmark and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Jun 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part 1: Occurrence of DLTs During Cycle 1 of Sym015 Administration (time frame: Cycle 1, the initial 28-day period of Q2W dosing). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02648724, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2022.