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TerminatedNCT02906670Updated Aug 28, 2020Results posted

Sym013 (Pan-HER) in Patients With Advanced Epithelial Malignancies

A Phase 1/2 interventional study of Sym013 in Oncology, sponsored by Symphogen A/S. Terminated at 3 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-08-28.

Sponsored by Symphogen A/S · Phase 1/2, Interventional, and Treatment

Why this study was terminated
Business reasons
Phase
Phase 1/2
Study type
Interventional
Enrollment
32
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study summary

This is the first study to test Sym013 (Pan-HER) in humans. The primary purpose of this study is to see if Sym013 is safe and effective for patients with advanced epithelial malignancies without available therapeutic options.

Read the detailed description

This is an open-label, multicenter trial composed of 2 parts in which Sym013 will be evaluated when administered by intravenous infusion in patients with advanced epithelial malignancies without available therapeutic options.

Part 1 is a Phase 1a dose-escalation evaluating weekly (Q1W) and every second week (Q2W) schedules of administration in separate dose-escalation cohorts to determine the recommended phase 2 dose (RP2D) and regimen of Sym013.

Part 2 is a Phase 2a dose-expansion at the RP2D and regimen. Four (4) dose-expansion cohorts will be evaluated in this part of the trial and will be selected based upon findings from Part 1, additional preclinical data, and additional clinical data available at that time from other agents inhibiting these targets. Patients will be entered, depending upon either a defined molecular profile or profiles, or their underlying malignancy, to 1 of 4 corresponding expansion cohorts: Cohort A, Cohort B, Cohort C, or Cohort D.

02

Conditions studied

  • Oncology

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Keywords

  • Epithelial malignancies
03

In context

Neoplasms

9,365 studies on the registry are indexed under Neoplasms; 2,489 are open to participants now.

This study's enrollment of 32 is below the median of 50 across 7,253 interventional studies indexed under Neoplasms.

Browse Neoplasms studies →

Lead sponsor

Symphogen A/S is the lead sponsor of 14 studies on the registry; none are open to participants now.

Of its 10 completed or terminated interventional studies of FDA-regulated products, 7 (70%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

Main inclusion criteria all patients, Part 1 and Part 2:

  • Male or female, at least 18 years of age at the time of informed consent
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
  • Life expectancy >3 months assessed during Screening
  • Documented (histologically- or cytologically-proven) epithelial malignancy that is locally advanced or metastatic, having received all therapy known to confer clinical benefit

Additional inclusion criteria applicable to Part 2 ONLY:

  • Epithelial malignancy (tumor types to be determined), measurable according to RECIST v1.1 that has been confirmed by computed tomography (CT) or magnetic resonance imaging (MRI) within 4 weeks prior to C1/D1
  • Willingness to undergo a pre-and post-dosing biopsy (total of 2 biopsies) from primary or metastatic tumor site(s) considered safe for biopsy

Exclusion criteria

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.
  • Part 2 ONLY: Radiotherapy against target lesions within 4 weeks prior to C1/D1, unless there is documented progression of the lesion following radiotherapy
  • Immunosuppressive or systemic hormonal therapy (>10 mg daily prednisone equivalent) 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 allowed exceptions

  • Central nervous system (CNS) malignancies including:

    1. Primary malignancies of the CNS
    2. 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 metastatic 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
  • Non-healing wounds on any part of the body
  • Active thrombosis, or a history of deep vein thrombosis or pulmonary embolism, within 4 weeks prior to C1/D1, unless adequately treated and stable
  • Active uncontrolled bleeding or a known bleeding diathesis
  • Significant gastrointestinal abnormalities
  • Significant cardiovascular disease or condition
  • Abnormal hematologic, renal or hepatic function
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
32 participants (actual)

Study arms

  • Experimental
    1 mg/kg Q1W

    Phase 1a: Patients are administered a weekly dose of 1 mg/kg of Sym013 until unacceptable toxicity, progressive disease, termination of the trial or patient decision to withdraw.

    Drug: Sym013

  • Experimental
    2 mg/kg Q1W

    Phase 1a: Patients are administered a weekly dose of 2 mg/kg of Sym013 until unacceptable toxicity, progressive disease, termination of the trial or patient decision to withdraw.

    Drug: Sym013

  • Experimental
    4 mg/kg Q1W

    Phase 1a: Patients are administered a weekly dose of 4 mg/kg of Sym013 until unacceptable toxicity, progressive disease, termination of the trial or patient decision to withdraw.

    Drug: Sym013

  • Experimental
    6 mg/kg Q1W + Prophylaxis

    Phase 1a: Patients are administered a weekly dose of 6 mg/kg of Sym013 + premedication until unacceptable toxicity, progressive disease, termination of the trial or patient decision to withdraw. Premedications for infusion-related reactions included glucocorticoids and an antihistamine (H1 antagonist) prior to each dose of Pan-HER from the beginning of the study. As of Protocol Amendment 5, additional premedications were added which included montelukast, dexamethasone, antihistamine (H2 antagonist), and acetaminophen.

    Drug: Sym013

  • Experimental
    9 mg/kg Q1W + Prophylaxis

    Phase 1a: Patients are administered a weekly dose of 9 mg/kg of Sym013 + premedication until unacceptable toxicity, progressive disease, termination of the trial or patient decision to withdraw. Premedications for infusion-related reactions included glucocorticoids and an antihistamine (H1 antagonist) prior to each dose of Pan-HER from the beginning of the study. As of Protocol Amendment 5, additional premedications were added which included montelukast, dexamethasone, antihistamine (H2 antagonist), and acetaminophen.

    Drug: Sym013

  • Experimental
    6 mg/kg Q2W

    Phase 1a: Patients are administered a dose of 6 mg/kg of Sym013 every second week until unacceptable toxicity, progressive disease, termination of the trial or patient decision to withdraw.

    Drug: Sym013

  • Experimental
    9 mg/kg Q2W

    Phase 1a: Patients are administered a dose of 9 mg/kg of Sym013 every second week until unacceptable toxicity, progressive disease, termination of the trial or patient decision to withdraw.

    Drug: Sym013

  • Experimental
    9 mg/kg Q2W + Prophylaxis

    Phase 1a: Patients are administered a dose of 9 mg/kg of Sym013 + premedication every second week until unacceptable toxicity, progressive disease, termination of the trial or patient decision to withdraw. Premedications for infusion-related reactions included glucocorticoids and an antihistamine (H1 antagonist) prior to each dose of Pan-HER from the beginning of the study. As of Protocol Amendment 5, additional premedications were added which included montelukast, dexamethasone, antihistamine (H2 antagonist), and acetaminophen.

    Drug: Sym013

  • Experimental
    12 mg/kg Q2W + Prophylaxis

    Phase 1a: Patients are administered a dose of 12 mg/kg of Sym013 + premedication every second week until unacceptable toxicity, progressive disease, termination of the trial or patient decision to withdraw. Premedications for infusion-related reactions included glucocorticoids and an antihistamine (H1 antagonist) prior to each dose of Pan-HER from the beginning of the study. As of Protocol Amendment 5, additional premedications were added which included montelukast, dexamethasone, antihistamine (H2 antagonist), and acetaminophen.

    Drug: Sym013

  • Experimental
    15 mg/kg Q2W + Prophylaxis

    Phase 1a: Patients are administered a dose of 15 mg/kg of Sym013 + premedication every second week until unacceptable toxicity, progressive disease, termination of the trial or patient decision to withdraw. Premedications for infusion-related reactions included glucocorticoids and an antihistamine (H1 antagonist) prior to each dose of Pan-HER from the beginning of the study. As of Protocol Amendment 5, additional premedications were added which included montelukast, dexamethasone, antihistamine (H2 antagonist), and acetaminophen.

    Drug: Sym013

  • Experimental
    Phase 2a Dose-Expansion Cohort A

    Part 2 is a Phase 2a dose-expansion with Sym013 at the RP2D and regimen. One (1) of 4 tumor types to be evaluated in this arm of the trial will be selected based upon findings from Part 1, additional preclinical data, and additional clinical data available at that time from other agents inhibiting these targets.

    Drug: Sym013

  • Experimental
    Phase 2a Dose-Expansion Cohort B

    Part 2 is a Phase 2a dose-expansion with Sym013 at the RP2D and regimen. One (1) of 4 tumor types to be evaluated in this arm of the trial will be selected based upon findings from Part 1, additional preclinical data, and additional clinical data available at that time from other agents inhibiting these targets.

    Drug: Sym013

  • Experimental
    Phase 2a Dose-Expansion Cohort C

    Part 2 is a Phase 2a dose-expansion with Sym013 at the RP2D and regimen. One (1) of 4 tumor types to be evaluated in this arm of the trial will be selected based upon findings from Part 1, additional preclinical data, and additional clinical data available at that time from other agents inhibiting these targets.

    Drug: Sym013

  • Experimental
    Phase 2a Dose-Expansion Cohort D

    Part 2 is a Phase 2a dose-expansion with Sym013 at the RP2D and regimen. One (1) of 4 tumor types to be evaluated in this arm of the trial will be selected based upon findings from Part 1, additional preclinical data, and additional clinical data available at that time from other agents inhibiting these targets.

    Drug: Sym013

Interventions

  • DrugSym013

    Sym013 is a recombinant antibody mixture containing 6 humanized immunoglobulin G1 (IgG1) monoclonal antibodies (mAbs), which bind specifically to non-overlapping epitopes or domains on the epidermal growth factor receptor (EGFR), and the human epidermal growth factor receptors (HER) HER2 and HER3.

    Also known as: Pan-HER

06

What researchers measure

Primary outcomes

  1. Part 1: Assess the Safety and Tolerability of Sym013 When Administered Either Q1W or Q2W to Separate Dose-escalation Cohorts of Patients.

    Assess the occurrence of dose-limiting toxicities (DLTs) during Cycle 1 of Sym013 administration.

    Time frame: 24 months

  2. Part 2: Evaluate the Antitumor Effect of Sym013 When Administered at the RP2D and Regimen to Patients.

    No data were collected for this Outcome Measures as Part 2 of the trial was never initiated.

    Time frame: 24 months

Secondary outcomes

  1. Part 1: Determine the RP2D and Regimen of Sym013.

    No RP2D or regimen of Sym013 was determined as the trial was prematurely terminated

    Time frame: 24 months

  2. Parts 1 and 2: Evaluate the Immunogenicity of Sym013.

    Serum sampling to assess the potential for anti-drug antibody (ADA) formation was not analyzed as the trial was prematurely terminated

    Time frame: 42 months

  3. Parts 1 and 2: Area Under the Concentration-time Curve Extrapolated to Infinity (AUC).

    Will be estimated using non-compartmental methods and actual time points.

    Time frame: 0, 2, 4, 8, 24, 48, 168 hours and 336 hours if Q2W

  4. Parts 1 and 2: Maximum Concentration (Cmax) and Trough Concentration (Ctrough) - Mean Values.

    Will be derived from observed data.

    Time frame: 0, 2, 4, 8, 24, 48, 168 hours and 336 hours if Q2W

  5. Parts 1 and 2: Time to Reach Maximum Concentration (Tmax).

    Will be derived from observed data. End of infusion was defined as time zero (0)

    Time frame: 0, 2, 4, 8, 24, 48, 168 hours and 336 hours if Q2W

  6. Parts 1 and 2: Elimination Half-life (T½).

    Will be estimated using non-compartmental methods and actual time points

    Time frame: 0, 2, 4, 8, 24, 48, 168 hours and 336 hours if Q2W

  7. Parts 1 and 2: Clearance (CL).

    Will be estimated using non-compartmental methods and actual time points.

    Time frame: 0, 2, 4, 8, 24, 48, 168 hours and 336 hours if Q2W

07

Results

Posted Aug 28, 2020

Participant flow

Patients were only recruited for Part 1; a recommended Phase 2 dose (RP2D) could not be established and the part 2 cohorts A, B, C and were not initiated.

Cohort 1, QW
Participant flow — Cohort 1, QW
Milestone1 mg/kg Q1W2 mg/kg Q1W4 mg/kg Q1W6 mg/kg Q1W + Prophylaxis9 mg/kg Q1W + Prophylaxis6 mg/kg Q2W9 mg/kg Q2W9 mg/kg Q2W + Prophylaxis12 mg/kg Q2W + Prophylaxis15 mg/kg Q2W + Prophylaxis
Started1000000000
Completed0000000000
Not completed1000000000
Withdrew: Radiological progression1000000000
Cohort 2, QW
Participant flow — Cohort 2, QW
Milestone1 mg/kg Q1W2 mg/kg Q1W4 mg/kg Q1W6 mg/kg Q1W + Prophylaxis9 mg/kg Q1W + Prophylaxis6 mg/kg Q2W9 mg/kg Q2W9 mg/kg Q2W + Prophylaxis12 mg/kg Q2W + Prophylaxis15 mg/kg Q2W + Prophylaxis
Started0100000000
Completed0000000000
Not completed0100000000
Withdrew: Radiological progression0100000000
Cohort 3, QW
Participant flow — Cohort 3, QW
Milestone1 mg/kg Q1W2 mg/kg Q1W4 mg/kg Q1W6 mg/kg Q1W + Prophylaxis9 mg/kg Q1W + Prophylaxis6 mg/kg Q2W9 mg/kg Q2W9 mg/kg Q2W + Prophylaxis12 mg/kg Q2W + Prophylaxis15 mg/kg Q2W + Prophylaxis
Started0040000000
Completed0000000000
Not completed0040000000
Withdrew: Radiological progression0020000000
Withdrew: Lack of clinical benefit0020000000
Cohort 4, Q2W
Participant flow — Cohort 4, Q2W
Milestone1 mg/kg Q1W2 mg/kg Q1W4 mg/kg Q1W6 mg/kg Q1W + Prophylaxis9 mg/kg Q1W + Prophylaxis6 mg/kg Q2W9 mg/kg Q2W9 mg/kg Q2W + Prophylaxis12 mg/kg Q2W + Prophylaxis15 mg/kg Q2W + Prophylaxis
Started0000030000
Completed0000000000
Not completed0000030000
Withdrew: Radiological progression0000010000
Withdrew: Clinical progression0000020000
Cohort 5, Q2W
Participant flow — Cohort 5, Q2W
Milestone1 mg/kg Q1W2 mg/kg Q1W4 mg/kg Q1W6 mg/kg Q1W + Prophylaxis9 mg/kg Q1W + Prophylaxis6 mg/kg Q2W9 mg/kg Q2W9 mg/kg Q2W + Prophylaxis12 mg/kg Q2W + Prophylaxis15 mg/kg Q2W + Prophylaxis
Started0000007000
Completed0000000000
Not completed0000007000
Withdrew: Radiological progression0000004000
Withdrew: Clinical progression0000001000
Withdrew: Adverse event0000001000
Withdrew: Lack of clinical benefit0000001000
Cohort 5P, Q2W
Participant flow — Cohort 5P, Q2W
Milestone1 mg/kg Q1W2 mg/kg Q1W4 mg/kg Q1W6 mg/kg Q1W + Prophylaxis9 mg/kg Q1W + Prophylaxis6 mg/kg Q2W9 mg/kg Q2W9 mg/kg Q2W + Prophylaxis12 mg/kg Q2W + Prophylaxis15 mg/kg Q2W + Prophylaxis
Started0000000300
Completed0000000000
Not completed0000000300
Withdrew: Radiological progression0000000200
Withdrew: Adverse event0000000100
Cohort 6P, Q2W
Participant flow — Cohort 6P, Q2W
Milestone1 mg/kg Q1W2 mg/kg Q1W4 mg/kg Q1W6 mg/kg Q1W + Prophylaxis9 mg/kg Q1W + Prophylaxis6 mg/kg Q2W9 mg/kg Q2W9 mg/kg Q2W + Prophylaxis12 mg/kg Q2W + Prophylaxis15 mg/kg Q2W + Prophylaxis
Started0000000040
Completed0000000000
Not completed0000000040
Withdrew: Radiological progression0000000010
Withdrew: Clinical progression0000000030
Cohort 4P, QW
Participant flow — Cohort 4P, QW
Milestone1 mg/kg Q1W2 mg/kg Q1W4 mg/kg Q1W6 mg/kg Q1W + Prophylaxis9 mg/kg Q1W + Prophylaxis6 mg/kg Q2W9 mg/kg Q2W9 mg/kg Q2W + Prophylaxis12 mg/kg Q2W + Prophylaxis15 mg/kg Q2W + Prophylaxis
Started0003000000
Completed0000000000
Not completed0003000000
Withdrew: Radiological progression0003000000
Cohort 7P, Q2W
Participant flow — Cohort 7P, Q2W
Milestone1 mg/kg Q1W2 mg/kg Q1W4 mg/kg Q1W6 mg/kg Q1W + Prophylaxis9 mg/kg Q1W + Prophylaxis6 mg/kg Q2W9 mg/kg Q2W9 mg/kg Q2W + Prophylaxis12 mg/kg Q2W + Prophylaxis15 mg/kg Q2W + Prophylaxis
Started0000000003
Completed0000000000
Not completed0000000003
Withdrew: Adverse event0000000001
Withdrew: Physician decision0000000001
Withdrew: More than 3 dose-reduction of pan-her0000000001
Cohort 5P, QW
Participant flow — Cohort 5P, QW
Milestone1 mg/kg Q1W2 mg/kg Q1W4 mg/kg Q1W6 mg/kg Q1W + Prophylaxis9 mg/kg Q1W + Prophylaxis6 mg/kg Q2W9 mg/kg Q2W9 mg/kg Q2W + Prophylaxis12 mg/kg Q2W + Prophylaxis15 mg/kg Q2W + Prophylaxis
Started0000300000
Completed0000000000
Not completed0000300000
Withdrew: Radiological progression0000300000

Outcome measures

PrimaryPart 1: Assess the Safety and Tolerability of Sym013 When Administered Either Q1W or Q2W to Separate Dose-escalation Cohorts of Patients.

Assess the occurrence of dose-limiting toxicities (DLTs) during Cycle 1 of Sym013 administration.

Time frame:
24 months
Reported as:
Count of participants · Participants
Part 1: Assess the Safety and Tolerability of Sym013 When Administered Either Q1W or Q2W to Separate Dose-escalation Cohorts of Patients.
Participants1 mg/kg Q1W2 mg/kg Q1W4 mg/kg Q1W6 mg/kg Q1W + Prophylaxis9 mg/kg Q1W + Prophylaxis6 mg/kg Q2W9 mg/kg Q2W9 mg/kg Q2W + Prophylaxis12 mg/kg Q2W + Prophylaxis15 mg/kg Q2W + Prophylaxis
Part 1: Assess the Safety and Tolerability of Sym013 When Administered Either Q1W or Q2W to Separate Dose-escalation Cohorts of Patients.0000002002
PrimaryPart 2: Evaluate the Antitumor Effect of Sym013 When Administered at the RP2D and Regimen to Patients.

No data were collected for this Outcome Measures as Part 2 of the trial was never initiated.

Time frame:
24 months

No measurements were reported for this outcome.

SecondaryPart 1: Determine the RP2D and Regimen of Sym013.

No RP2D or regimen of Sym013 was determined as the trial was prematurely terminated

Time frame:
24 months

No measurements were reported for this outcome.

SecondaryParts 1 and 2: Evaluate the Immunogenicity of Sym013.

Serum sampling to assess the potential for anti-drug antibody (ADA) formation was not analyzed as the trial was prematurely terminated

Time frame:
42 months

No measurements were reported for this outcome.

SecondaryParts 1 and 2: Area Under the Concentration-time Curve Extrapolated to Infinity (AUC).

Will be estimated using non-compartmental methods and actual time points.

Time frame:
0, 2, 4, 8, 24, 48, 168 hours and 336 hours if Q2W
Reported as:
Mean · h*µg/mL
Parts 1 and 2: Area Under the Concentration-time Curve Extrapolated to Infinity (AUC).
h*µg/mL1 mg/kg Q1W2 mg/kg Q1W4 mg/kg Q1W6 mg/kg Q1W + Prophylaxis9 mg/kg Q1W + Prophylaxis6 mg/kg Q2W9 mg/kg Q2W and 9 mg/kg Q2W + Prophylaxis12 mg/kg Q2W + Prophylaxis15 mg/kg Q2W + ProphylaxisPhase 2a Dose-Expansion Cohort APhase 2a Dose-Expansion Cohort BPhase 2a Dose-Expansion Cohort CPhase 2a Dose-Expansion Cohort D
Hu1277, 1st dose (1st PK profile), AUCNA22270 ± 43NA ± NA550 ± NA280 ± NA440 ± 24NA ± NA8600 ± NA————
Hu1565, 1st dose (1st PK profile), AUCNANANA ± NA1480 ± NA2200 ± NANA ± NA2900 ± 11003900 ± 670NA ± NA————
Hu4384, 1st dose (1st PK profile), AUCNANA750 ± 1101200 ± 2302100 ± 6401000 ± 3102200 ± 9602600 ± 57019000 ± NA————
Hu4517, 1st dose (1st PK profile), AUCNA267880 ± 1301400 ± 3202300 ± 6801200 ± 2502200 ± 6902600 ± 71017000 ± NA————
Hu5038, 1st dose (1st PK profile), AUCNANA860 ± 851200 ± 2802000 ± 6801100 ± 3102000 ± 5802500 ± 100013500 ± NA————
Hu5082, 1st dose (1st PK profile), AUCNA6282900 ± 2303900 ± 11003900 ± NA4000 ± 15006000 ± 18008900 ± 370019800 ± NA————
Hu1277, 3rd/4th dose (2nd PK profile), AUCNANANA ± NANA ± NANA ± NANA ± NA760 ± 300NA ± NA—————
Hu1565, 3rd/4th dose (2nd PK profile), AUCNANA1300 ± 720NA ± NA2100 ± NANA ± NANA ± NANA ± NA—————
Hu4384, 3rd/4th dose (2nd PK profile), AUCNANA1600 ± 1000NA ± NANA ± NANA ± NA1800 ± 570NA ± NA—————
Hu4517, 3rd/4th dose (2nd PK profile), AUCNA3401800 ± 12002100 ± 2005600 ± 46001700 ± 4002500 ± 12003100 ± 870—————
Hu5038, 3rd/4th dose (2nd PK profile), AUCNANA1600 ± 8701500 ± 4704000 ± 31001800 ± NA2500 ± 12004800 ± NA—————
Hu5082, 3rd/4th dose (2nd PK profile), AUCNA8802600 ± 7406800 ± NANA ± NA3800 ± NA9900 ± 26009700 ± NA—————
SecondaryParts 1 and 2: Maximum Concentration (Cmax) and Trough Concentration (Ctrough) - Mean Values.

Will be derived from observed data.

Time frame:
0, 2, 4, 8, 24, 48, 168 hours and 336 hours if Q2W
Reported as:
Mean · µg/mL
Parts 1 and 2: Maximum Concentration (Cmax) and Trough Concentration (Ctrough) - Mean Values.
µg/mL1 mg/kg Q1W2 mg/kg Q1W4 mg/kg Q1W6 mg/kg Q1W + Prophylaxis9 mg/kg Q1W + Prophylaxis6 mg/kg Q2W9 mg/kg Q2W and 9 mg/kg Q2W + Prophylaxis12 mg/kg Q2W + Prophylaxis15 mg/kg Q2W + Prophylaxis
Hu1277, 1st dose (1st PK profile), Cmax0.781.810 ± 3.015 ± 3.123 ± 2.612 ± 2.520 ± 9.025 ± 3.766 ± 21
Hu1277, 1st dose (1st PK profile), CtroughNANANA ± NANA ± NANA ± NANA ± NANA ± NANA ± NA16 ± NA
Hu1565, 1st dose (1st PK profile), Cmax3.24.921 ± 4.331 ± 5.644 ± 3.125 ± 3.943 ± 1748 ± 6.3130 ± 34
Hu1565, 1st dose (1st PK profile), CtroughNANANA ± NA0.82 ± NA0.85 ± NANA ± NANA ± NANA ± NA50 ± NA
Hu4384, 1st dose (1st PK profile), Cmax2.54.116 ± 6.222 ± 3.230 ± 2.316 ± 3.030 ± 1131 ± 3.792 ± 45
Hu4384, 1st dose (1st PK profile), CtroughNA0.320.59 ± 0.361.5 ± 0.93.3 ± 1.9NA ± NA0.69 ± 0.551.4 ± NA19 ± 23
Hu4517, 1st dose (1st PK profile), Cmax3.04.717 ± 2.227 ± 4.536 ± 4.220 ± 2.937 ± 1638 ± 3.9110 ± 55
Hu4517, 1st dose (1st PK profile), CtroughNA0.380.72 ± 0.311.4 ± 0.93.0 ± 1.50.43 ± 0.050.66 ± 0.220.61 ± 0.2116 ± 22
Hu5038, 1st dose (1st PK profile), Cmax2.95.616 ± 2.324 ± 4.031 ± 2.418 ± 2.929 ± 1234 ± 3.987 ± 32
Hu5038, 1st dose (1st PK profile), CtroughNANA0.79 ± 0.241.3 ± 1.12.8 ± 1.8NA ± NA0.57 ± 0.240.86 ± 0.2915 ± 19
Hu5082, 1st dose (1st PK profile), Cmax7.29.842 ± 6.555 ± 1167 ± 6.339 ± 1277 ± 3289 ± 14160 ± 45
Hu5082, 1st dose (1st PK profile), CtroughNA0.924.8 ± 0.79.3 ± 6.316 ± 112.5 ± 2.24.3 ± 2.07.8 ± 3.734 ± 43
Hu1277, 3rd/4th dose (2nd PK profile), Cmax2.53.011 ± 1.317 ± 2.330 ± 6.613 ± 1.628 ± 1129 ± 3.9—
Hu1277, 3rd/4th dose (2nd PK profile), CtroughNANANA ± NANA ± NANA ± NANA ± NANA ± NANA ± NA—
Hu1565, 3rd/4th dose (2nd PK profile), Cmax9.57.022 ± 3.035 ± 8.754 ± 1029 ± 5.757 ± 2160 ± 8.8—
Hu1565, 3rd/4th dose (2nd PK profile), CtroughNANA0.49 ± NA8.9 ± NA2.5 ± 0.3NA ± NANA ± NANA ± NA—
Hu4384, 3rd/4th dose (2nd PK profile), Cmax8.36.117 ± 2.630 ± 4.248 ± 2119 ± 3.637 ± 1334 ± 3.6—
Hu4384, 3rd/4th dose (2nd PK profile), CtroughNANA1.9 ± 0.86.6 ± 4.710 ± 7.0NA ± NA1.5 ± 1.8NA ± NA—
Hu4517, 3rd/4th dose (2nd PK profile), Cmax8.47.519 ± 2.531 ± 8.157 ± 1921 ± 0.843 ± 1345 ± 5.6—
Hu4517, 3rd/4th dose (2nd PK profile), CtroughNA0.592.1 ± 0.94.9 ± 3.45.4 ± 1.00.66 ± 0.221.3 ± 1.10.75 ± 0.41—
Hu5038, 3rd/4th dose (2nd PK profile), Cmax7.78.318 ± 2.129 ± 4.044 ± 9.121 ± 4.142 ± 1441 ± 3.9—
Hu5038, 3rd/4th dose (2nd PK profile), CtroughNANA1.9 ± 0.43.8 ± 2.74.5 ± 1.90.81 ± NA1.4 ± 1.22.6 ± NA—
Hu5082, 3rd/4th dose (2nd PK profile), Cmax101547 ± 9.697 ± 4282 ± 2351 ± 6.899 ± 31120 ± 21—
Hu5082, 3rd/4th dose (2nd PK profile), CtroughNA1.97.1 ± 6.128 ± 1631 ± 206.8 ± 6.86.2 ± 6.222 ± 22—
SecondaryParts 1 and 2: Time to Reach Maximum Concentration (Tmax).

Will be derived from observed data. End of infusion was defined as time zero (0)

Time frame:
0, 2, 4, 8, 24, 48, 168 hours and 336 hours if Q2W
Reported as:
Mean · h
Parts 1 and 2: Time to Reach Maximum Concentration (Tmax).
h1 mg/kg Q1W2 mg/kg Q1W4 mg/kg Q1W6 mg/kg Q1W + Prophylaxis9 mg/kg Q1W + Prophylaxis6 mg/kg Q2W9 mg/kg Q2W and 9 mg/kg Q2W + Prophylaxis12 mg/kg Q2W + Prophylaxis15 mg/kg Q2W + ProphylaxisPhase 2a Dose-Expansion Cohort APhase 2a Dose-Expansion Cohort BPhase 2a Dose-Expansion Cohort CPhase 2a Dose-Expansion Cohort D
Hu1277, 1st dose (1st PK profile), Tmax002.5 ± 1.92.0 ± 2.01.1 ± 1.00.69 ± 1.21.7 ± 1.90.91 ± 1.10.94 ± 1.6————
Hu1565, 1st dose (1st PK profile), Tmax002.5 ± 1.90.65 ± 1.12.3 ± 1.10.69 ± 1.21.9 ± 1.81.4 ± 1.02.2 ± 1.9————
Hu4384, 1st dose (1st PK profile), Tmax002.5 ± 1.90.65 ± 1.12.3 ± 1.10 ± 03.1 ± 5.41.3 ± 0.891.2 ± 2.1————
Hu4517, 1st dose (1st PK profile), Tmax002.5 ± 1.92.0 ± 2.01.1 ± 0.970 ± 01.3 ± 1.11.0 ± 1.10 ± 0————
Hu5038, 1st dose (1st PK profile), Tmax2.002.5 ± 1.92.0 ± 2.01.1 ± 0.970 ± 01.4 ± 1.31.0 ± 1.21.2 ± 2.1————
Hu5082, 1st dose (1st PK profile), Tmax002.5 ± 1.90.65 ± 1.11.1 ± 0.970.97 ± 1.21.1 ± 1.20.52 ± 1.06.4 ± 11————
Hu1277, 3rd/4th dose (2nd PK profile), Tmax7.000.48 ± 0.960 ± 01.3 ± 2.30.97 ± 1.40.94 ± 1.00 ± 0—————
Hu1565, 3rd/4th dose (2nd PK profile), Tmax7.000 ± 00 ± 02.5 ± 2.20.67 ± 1.41.5 ± 2.01.7 ± 2.4—————
Hu4384, 3rd/4th dose (2nd PK profile), Tmax7.001.0 ± 2.00 ± 02.5 ± 2.20.97 ± 1.41.2 ± 2.10 ± 0—————
Hu4517, 3rd/4th dose (2nd PK profile), Tmax7.001.4 ± 1.81.3 ± 2.31.3 ± 2.30.97 ± 1.40.91 ± 1.50 ± 0—————
Hu5038, 3rd/4th dose (2nd PK profile), Tmax7.000.48 ± 0.960 ± 01.3 ± 2.30.97 ± 1.40.94 ± 1.00 ± 0—————
Hu5082, 3rd/4th dose (2nd PK profile), Tmax002.9 ± 2.41.9 ± 2.02.5 ± 2.20.97 ± 1.44.0 ± 8.30.95 ± 1.3—————
SecondaryParts 1 and 2: Elimination Half-life (T½).

Will be estimated using non-compartmental methods and actual time points

Time frame:
0, 2, 4, 8, 24, 48, 168 hours and 336 hours if Q2W
Reported as:
Mean · H
Parts 1 and 2: Elimination Half-life (T½).
H1 mg/kg Q1W2 mg/kg Q1W4 mg/kg Q1W6 mg/kg Q1W + Prophylaxis9 mg/kg Q1W + Prophylaxis6 mg/kg Q2W9 mg/kg Q2W and 9 mg/kg Q2W + Prophylaxis12 mg/kg Q2W + Prophylaxis15 mg/kg Q2W + ProphylaxisPhase 2a Dose-Expansion Cohort APhase 2a Dose-Expansion Cohort BPhase 2a Dose-Expansion Cohort CPhase 2a Dose-Expansion Cohort D
Hu1277, 1st dose (1st PK profile), T½NA8.318 ± 4.126 ± 6.025 ± 5.821 ± 9.230 ± 2039 ± 7.256 ± 18————
Hu1565, 1st dose (1st PK profile), T½202936 ± 5.829 ± 2.433 ± 1035 ± 5.045 ± 1452 ± 8.266 ± 24————
Hu4384, 1st dose (1st PK profile), T½315039 ± 5.651 ± 7.962 ± 1247 ± 1656 ± 1973 ± 1392 ± 48————
Hu4517, 1st dose (1st PK profile), T½295039 ± 4.743 ± 5.056 ± 9.859 ± 1854 ± 1555 ± 1173 ± 32————
Hu5038, 1st dose (1st PK profile), T½273942 ± 4.042 ± 6.555 ± 1150 ± 1651 ± 1254 ± 2378 ± 44————
Hu5082, 1st dose (1st PK profile), T½NA5366 ± 7.083 ± 3096 ± 3390 ± 3396 ± 2997 ± 3493 ± 62————
Hu1277, 3rd/4th dose (2nd PK profile), T½NANA28 ± 9.637 ± 1.535 ± 7.727 ± 5.526 ± 731 ± NA—————
Hu1565, 3rd/4th dose (2nd PK profile), T½NA2043 ± 2650 ± 2243 ± NA39 ± 3.639 ± 8.348 ± NA—————
Hu4384, 3rd/4th dose (2nd PK profile), T½NA2569 ± 5094 ± 25152 ± 10544 ± 3.784 ± 4948 ± NA—————
Hu4517, 3rd/4th dose (2nd PK profile), T½NA3477 ± 5064 ± 2185 ± 2770 ± 3.079 ± 3561 ± 7.4—————
Hu5038, 3rd/4th dose (2nd PK profile), T½NA2069 ± 4062 ± 1177 ± 2859 ± 2278 ± 4164 ± 35—————
Hu5082, 3rd/4th dose (2nd PK profile), T½NA42111 ± 90137 ± 73175 ± 71119 ± 54103 ± 30177 ± 122—————
SecondaryParts 1 and 2: Clearance (CL).

Will be estimated using non-compartmental methods and actual time points.

Time frame:
0, 2, 4, 8, 24, 48, 168 hours and 336 hours if Q2W
Reported as:
Mean · mL/h/kg
Parts 1 and 2: Clearance (CL).
mL/h/kg1 mg/kg Q1W2 mg/kg Q1W4 mg/kg Q1W6 mg/kg Q1W + Prophylaxis9 mg/kg Q1W + Prophylaxis6 mg/kg Q2W9 mg/kg Q2W and 9 mg/kg Q2W + Prophylaxis12 mg/kg Q2W + Prophylaxis15 mg/kg Q2W + ProphylaxisPhase 2a Dose-Expansion Cohort APhase 2a Dose-Expansion Cohort BPhase 2a Dose-Expansion Cohort CPhase 2a Dose-Expansion Cohort D
Hu1277, 1st dose (1st PK profile), CLNA9.81.6 ± 0.26NA ± NA1.8 ± NA2.3 ± NA2.2 ± 0.12NA ± NA0.19 ± NA————
Hu1565, 1st dose (1st PK profile), CLNANANA ± NA0.82 ± NA0.82 ± NANA ± NA0.72 ± 0.310.64 ± 0.11NA ± NA————
Hu4384, 1st dose (1st PK profile), CLNANA0.63 ± 0.0920.6 ± 0.120.53 ± 0.190.72 ± 0.190.59 ± 0.310.55 ± 0.120.093 ± NA————
Hu4517, 1st dose (1st PK profile), CLNANA0.67 ± 0.110.64 ± 0.150.62 ± 0.220.77 ± 0.150.67 ± 0.290.69 ± 0.150.13 ± NA————
Hu5038, 1st dose (1st PK profile), CLNANA0.60 ± 0.0590.68 ± 0.170.62 ± 0.260.74 ± 0.180.64 ± 0.210.68 ± 0.240.14 ± NA————
Hu5082, 1st dose (1st PK profile), CLNA0.970.42 ± 0.0330.49 ± 0.140.70 ± NA0.50 ± 0.170.49 ± 0.130.46 ± 0.170.23 ± NA————
6Hu1277, 3rd/4th dose (2nd PK profile), CLNANANA ± NANA ± NANA ± NANA ± NA1.4 ± 0.54NA ± NA—————
Hu1565, 3rd/4th dose (2nd PK profile), CLNANA0.79 ± 0.37NA ± NA0.86 ± NANA ± NANA ± NANA ± NA—————
Hu4384, 3rd/4th dose (2nd PK profile), CLNANA0.36 ± 0.16NA ± NANA ± NANA ± NA0.63 ± 0.20NA ± NA—————
Hu4517, 3rd/4th dose (2nd PK profile), CLNA0.860.41 ± 0.200.42 ± 0.0410.35 ± 0.290.54 ± 0.130.62 ± 0.290.59 ± 0.17—————
Hu5038, 3rd/4th dose (2nd PK profile), CLNANA0.37 ± 0.150.55 ± 0.180.41 ± 0.310.42 ± NA0.55 ± 0.250.32 ± NA—————
Hu5082, 3rd/4th dose (2nd PK profile), CLNA0.690.49 ± 0.140.27 ± NANA ± NA0.48 ± NA0.29 ± 0.080.38 ± NA—————

Adverse events

Collected over All AEs will be recorded from signing of informed consent for participation in the trial. The recording period ends at the time of the 1 month follow-up Visit.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
1 mg/kg Q1W0/1 (0%)0/1 (0%)1/1 (100%)
2 mg/kg Q1W0/1 (0%)0/1 (0%)1/1 (100%)
4 mg/kg Q1W0/4 (0%)0/4 (0%)4/4 (100%)
6 mg/kg Q1W + Prophylaxis0/3 (0%)0/3 (0%)3/3 (100%)
9 mg/kg Q1W + Prophylaxis0/3 (0%)1/3 (33.3%)3/3 (100%)
6 mg/kg Q2W1/3 (33.3%)1/3 (33.3%)3/3 (100%)
9 mg/kg Q2W0/7 (0%)3/7 (42.9%)7/7 (100%)
9 mg/kg Q2W + Prophylaxis0/3 (0%)1/3 (33.3%)3/3 (100%)
12 mg/kg Q2W + Prophylaxis0/4 (0%)2/4 (50%)4/4 (100%)
15 mg/kg Q2W + Prophylaxis0/3 (0%)2/7 (28.6%)3/3 (100%)
Most frequent serious events
Showing 10 of 12
Most frequent serious events
Event1 mg/kg Q1W2 mg/kg Q1W4 mg/kg Q1W6 mg/kg Q1W + Prophylaxis9 mg/kg Q1W + Prophylaxis6 mg/kg Q2W9 mg/kg Q2W9 mg/kg Q2W + Prophylaxis12 mg/kg Q2W + Prophylaxis15 mg/kg Q2W + Prophylaxis
Dermatitis AcneiformSkin and subcutaneous tissue disorders0/10/10/40/31/30/30/70/30/42/7
Large intestinal obstructionGastrointestinal disorders0/10/10/40/31/30/30/70/30/40/7
DehydrationMetabolism and nutrition disorders0/10/10/40/30/30/30/71/30/40/7
Metastases to central nervous systemNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/10/10/40/30/31/30/70/30/40/7
Pericardial effusionCardiac disorders0/10/10/40/30/30/30/70/31/40/7
SepsisInfections and infestations0/10/10/40/30/30/30/70/31/40/7
Gastrointestinal painGastrointestinal disorders0/10/10/40/30/30/30/70/30/41/7
Intestinal obstructionGastrointestinal disorders0/10/10/40/30/30/30/70/30/41/7
OesophagitisGastrointestinal disorders0/10/10/40/30/30/30/70/30/41/7
StomatitisGastrointestinal disorders0/10/10/40/30/30/31/70/30/40/7
Most frequent other events
Showing 10 of 126
Most frequent other events
Event1 mg/kg Q1W2 mg/kg Q1W4 mg/kg Q1W6 mg/kg Q1W + Prophylaxis9 mg/kg Q1W + Prophylaxis6 mg/kg Q2W9 mg/kg Q2W9 mg/kg Q2W + Prophylaxis12 mg/kg Q2W + Prophylaxis15 mg/kg Q2W + Prophylaxis
StomatitisGastrointestinal disorders0/10/14/42/32/32/36/71/33/42/3
NauseaGastrointestinal disorders0/10/10/40/30/31/31/70/31/43/3
ConstipationGastrointestinal disorders0/11/10/40/30/30/31/71/30/40/3
Abdominal pain lowerGastrointestinal disorders0/11/11/40/30/30/30/70/30/40/3
DysphagaiGastrointestinal disorders0/11/10/40/30/30/30/70/30/40/3
Dermatitis acneiformSkin and subcutaneous tissue disorders0/10/12/43/33/32/35/71/31/42/3
PruritusSkin and subcutaneous tissue disorders1/10/11/40/30/30/31/71/32/40/3
Rash maculo-papularSkin and subcutaneous tissue disorders0/11/11/42/30/30/31/70/30/41/3
Dry skinSkin and subcutaneous tissue disorders1/10/10/40/30/30/31/71/30/41/3
Incision site erythemaInjury, poisoning and procedural complications0/11/10/40/30/30/30/70/30/40/3

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)1 mg/kg Q1W2 mg/kg Q1W4 mg/kg Q1W6 mg/kg Q1W + Prophylaxis9 mg/kg Q1W + Prophylaxis6 mg/kg Q2W9 mg/kg Q2W9 mg/kg Q2W + Prophylaxis12 mg/kg Q2W + Prophylaxis15 mg/kg Q2W + ProphylaxisTotal
<=18 years00000000000
Between 18 and 65 years113212611220
>=65 years001121123112
Age, Continuous
Age, Continuous(Years)1 mg/kg Q1W2 mg/kg Q1W4 mg/kg Q1W6 mg/kg Q1W + Prophylaxis9 mg/kg Q1W + Prophylaxis6 mg/kg Q2W9 mg/kg Q2W9 mg/kg Q2W + Prophylaxis12 mg/kg Q2W + Prophylaxis15 mg/kg Q2W + ProphylaxisTotal
Mean54.057.059.3 ± 9.7458.0 ± 6.0863.3 ± 11.2456.0 ± 12.1251.6 ± 11.5967.3 ± 10.0263.8 ± 13.7759.7 ± 8.0258.7 ± 10.48
Sex: Female, Male
Sex: Female, Male(Participants)1 mg/kg Q1W2 mg/kg Q1W4 mg/kg Q1W6 mg/kg Q1W + Prophylaxis9 mg/kg Q1W + Prophylaxis6 mg/kg Q2W9 mg/kg Q2W9 mg/kg Q2W + Prophylaxis12 mg/kg Q2W + Prophylaxis15 mg/kg Q2W + ProphylaxisTotal
Female001021331112
Male113312403220
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)1 mg/kg Q1W2 mg/kg Q1W4 mg/kg Q1W6 mg/kg Q1W + Prophylaxis9 mg/kg Q1W + Prophylaxis6 mg/kg Q2W9 mg/kg Q2W9 mg/kg Q2W + Prophylaxis12 mg/kg Q2W + Prophylaxis15 mg/kg Q2W + ProphylaxisTotal
Hispanic or Latino00120011016
Not Hispanic or Latino113133624226
Unknown or Not Reported00000000000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)1 mg/kg Q1W2 mg/kg Q1W4 mg/kg Q1W6 mg/kg Q1W + Prophylaxis9 mg/kg Q1W + Prophylaxis6 mg/kg Q2W9 mg/kg Q2W9 mg/kg Q2W + Prophylaxis12 mg/kg Q2W + Prophylaxis15 mg/kg Q2W + ProphylaxisTotal
American Indian or Alaska Native00000000000
Asian00100000001
Native Hawaiian or Other Pacific Islander00000000000
Black or African American00001101003
White113322624327
More than one race00000000000
Unknown or Not Reported00000010001
Region of Enrollment
Region of Enrollment(participants)1 mg/kg Q1W2 mg/kg Q1W4 mg/kg Q1W6 mg/kg Q1W + Prophylaxis9 mg/kg Q1W + Prophylaxis6 mg/kg Q2W9 mg/kg Q2W9 mg/kg Q2W + Prophylaxis12 mg/kg Q2W + Prophylaxis15 mg/kg Q2W + ProphylaxisTotal
United States114333734332
Body Mass Index (BMI)
Body Mass Index (BMI)(kg/m^2)1 mg/kg Q1W2 mg/kg Q1W4 mg/kg Q1W6 mg/kg Q1W + Prophylaxis9 mg/kg Q1W + Prophylaxis6 mg/kg Q2W9 mg/kg Q2W9 mg/kg Q2W + Prophylaxis12 mg/kg Q2W + Prophylaxis15 mg/kg Q2W + ProphylaxisTotal
Mean36.226.3027.45 ± 7.54326.00 ± 2.89326.93 ± 2.40927.13 ± 2.12226.84 ± 5.82824.03 ± 6.58421.98 ± 1.98131.83 ± 9.17826.75 ± 5.575
08

Study locations

3 sites
  • Vanderbilt University Medical Center
    Nashville, Tennessee 37232, United States
  • South Texas Accelerated Research Therapeutics, LLC
    San Antonio, Texas 78229, United States
  • NEXT Oncology
    San Antonio, Texas 78240, United States
09

References and documents

Publications

  • Berlin J, Tolcher AW, Ding C, Whisenant JG, Horak ID, Wood DL, Nadler PI, Hansen UH, Lantto J, Skartved NJO, Pedersen MW, Patnaik A. First-in-human trial exploring safety, antitumor activity, and pharmacokinetics of Sym013, a recombinant pan-HER antibody mixture, in advanced epithelial malignancies. Invest New Drugs. 2022 Jun;40(3):586-595. doi: 10.1007/s10637-022-01217-7. Epub 2022 Feb 3. PubMed 35113285 ↗

Study documents

  • Study protocol · Jun 14, 2018
  • Statistical analysis plan · Apr 5, 2019

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 28, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02906670
Lead sponsor
Symphogen A/S
Responsible party
Sponsor
First posted
Sep 20, 2016
Start date
Nov 1, 2016
Primary completion
Jun 2019
Completion
Jun 2019
Results posted
Aug 28, 2020
Last update
Aug 28, 2020

Study contacts

Jordan Berlin, MD
principal investigator · Vanderbilt University Medical Center

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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