Locally Advanced or Metastatic Solid Tumor(s)Phase 1/2NCT04424641
A Study on the Safety of GEN1044 (DuoBody®-CD3x5T4) in Patients With Malignant Solid Tumors
A Phase 1/2 study testing GEN1044 is an immunoglobulin G1 (IgG1) bispecific antibody targeting CD3 and 5T4. in people with Locally Advanced or Metastatic Solid Tumor(s) and Prostate Cancer, run by Genmab at 6 sites in 4 countries.
Trial summary
The purpose of the trial is to evaluate the safety, determine the recommended Phase 2 dose (RP2D), and assess preliminary clinical activity of GEN1044 in patients with solid tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Locally Advanced or Metastatic Solid Tumor(s), Prostate Cancer, Esophageal Cancer
- What is being tested?
- GEN1044 is an immunoglobulin G1 (IgG1) bispecific antibody targeting CD3 and 5T4.
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 6 sitesin 4 countries
- Study dates
- 15 Jul 2020to 29 Oct 2021
- 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
- Dose-escalation part:
- Patient with locally advanced or metastatic solid tumor(s) (excluding patients with primary central nervous system [CNS] tumors), who has experienced disease progression while on standard therapy or is intolerant of, or not eligible for, standard therapy.
- Expansion part:
- Must have an advanced or metastatic, pathologically confirmed diagnosis of one of the following tumors: Uterine Cancer, Prostate Cancer, Esophageal Cancer, TNBC, SCCHN, NSCLC (both adenocarcinoma [ACC] and squamous cell carcinoma [SCC], Bladder Cancer.
- Both parts:
- Must sign an informed consent form (ICF) indicating that he or she understands the purpose of, and procedures required for the trial, and is willing to participate in the trial prior to any trial related assessments or procedures.
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- Must have measurable disease according to response assessment criteria relevant to the tumor type.
- Must have an Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score of 0-1 at Screening and on C1D1.
- A woman of reproductive potential must agree to use adequate contraception during the trial and for 4 months after the last GEN1044 administration. Adequate contraception is defined as highly effective methods of contraception.
Who cannot join
- Has an uncontrolled intercurrent illness, including but not limited to:
- Ongoing or active infection requiring intravenous treatment with anti-infective therapy
- Symptomatic congestive heart failure (grade III or IV as classified by the New York Heart Association), unstable angina pectoris or cardiac arrhythmia.
- Uncontrolled hypertension defined as systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg, despite optimal medical management.
- Ongoing or recent evidence of significant autoimmune disease. Patients with a history of grade 3 or higher immune-related adverse events that led to treatment discontinuation.
- Patients with a prior history of myositis, Guillain-Barré syndrome, or myasthenia gravis of any grade.
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- History of chronic liver disease or evidence of hepatic cirrhosis.
- History of non-infectious pneumonitis that has required steroids, or currently has pneumonitis.
- History of organ allograft (except for corneal transplant) or autologous or allogeneic bone marrow transplant, or stem cell rescue within 3 months prior to the first dose of GEN1044.
- Serious, non-healing wound, skin ulcer (of any grade), or bone fracture.
- Any history of intracerebral arteriovenous malformation, cerebral aneurysm, new or symptomatic brain metastases or stroke.
- Prior therapy:
- Radiotherapy: Radiotherapy within 14 days prior to first GEN1044 administration. Palliative radiotherapy will be allowed.
- Treatment with an anti-cancer agent (within 28 days or after at least 5 half-lives of the drug, whichever is shorter), prior to GEN1044 administration. Toxicities from previous anti-cancer therapies that have not resolved.
- Has a history of ≥ grade 2 cytokine release syndrome (CRS) with other CD3-based bispecifics, or a history of ≥ grade 3 allergic reactions to monoclonal antibody therapy as well as known or has known allergies, hypersensitivity, or intolerance to GEN1044 or its excipients.
Trial locations and contacts
6 sites in 4 countries.
6 sites in 4 countries
United States2 sites
MD Anderson Cancer Center
Houston, Texas, 77054
Tennesse Oncology, PLLC - Nashville
Nashville, Tennessee, 37203
Spain2 sites
Hospital Universitari Vall d'Hebron
Barcelona, 8035
Fundacion Jimenez Diaz
Madrid, 28040
Denmark1 site
Rigshospitalet (Copenhagen University Hospital)
Copenhagen, 2100
About this study
Official title: First-in-human, Open-label, Dose-escalation Trial With Expansion Cohorts to Evaluate Safety of GEN1044 in Subjects With Malignant Solid Tumors
The purpose of the trial is to evaluate the safety, determine the recommended Phase 2 dose (RP2D), and assess preliminary clinical activity of GEN1044 in patients with solid tumors.
Read the detailed description
The trial is an open-label, multi-center safety trial of GEN1044. The trial consists of two parts: a dose-escalation part (Phase 1) and an expansion part (Phase 2a). The expansion part of the trial will be initiated once the RP2D has been determined from Phase 1.
- Conditions
- Locally Advanced or Metastatic Solid Tumor(s), Prostate Cancer, Esophageal Cancer, Triple Negative Breast Cancer (TNBC), Squamous Cell Carcinoma of Head and Neck (SCCHN), Non-small Cell Lung Cancer (NSCLC)
- Being tested
- GEN1044 is an immunoglobulin G1 (IgG1) bispecific antibody targeting CD3 and 5T4.
- Medical subject headings
- Prostatic Neoplasms, Esophageal Neoplasms, Triple Negative Breast Neoplasms, Squamous Cell Carcinoma of Head and Neck, Carcinoma, Non-Small-Cell Lung, Urinary Bladder Neoplasms, Uterine Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GEN1044 is an immunoglobulin G1 (IgG1) bispecific antibody targeting CD3 and 5T4.Biological
Also called DuoBody®-CD3x5T4
GEN1044 will be administered intravenously in cycles of 21 days.
| Study group | Role | What they receive |
|---|---|---|
| GEN1044 | Experimental | Not described Receives: Biological: GEN1044 is an immunoglobulin G1 (IgG1) bispecific antibody targeting CD3 and 5T4. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Dose Limiting Toxicities (DLTs)
The DLT was defined as Grade (G) >= 3 cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome; any G3 or 4 hematologic and non-hematologic toxicity (with exceptions defined by the protocol); laboratory abnormality that required clinically significant medical intervention, led to hospitalization, persisted for >1 week, or resulted in a drug-induced liver injury; G3 or 4 febrile neutropenia; liver toxicity defined by Hy's law; any treatment-related toxicity that caused treatment discontinuation during Cycle 1; or any G5 toxicity.
Measured: From Day 1 to Day 21 of first cycle
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An serious adverse event (SAE) is defined as an AE that meets one of the following criteria: fatal or life-threatening; results in persistent or significant disability/incapacity; constitutes a congenital anomaly/birth defect; medically significant (an event that jeopardizes the participant or may require medical or surgical intervention to prevent one of the outcomes listed above [medical and scientific judgment must be exercised in deciding whether an AE is 'medically significant']); required inpatient hospitalization or prolongation of existing hospitalization. A TEAE is defined as an AE occurring or worsening between the first dose of GEN1044 and 30 days after the last dose received.
Measured: Day 1 through Day 263 (corresponding to maximum observed duration)
Number of Participants With Abnormal Laboratory Values
Number of participants with laboratory values of Grade >= 3 by NCI-CTCAE v5.0 are reported. The NCI-CTCAE is a descriptive terminology that is used for gradings (Grade 1-5) of Adverse Events (AEs) and of laboratory values; the latter being summarized here.
This table reports laboratory values graded only on the numerical value of the reported parameter and is therefore not graded by symptoms or signs. The abnormal laboratory values assessed by the investigator as being AEs are reported also in the AE table.
In case a participant reported multiple severity grades for a laboratory value, only the maximum grade was used.
Measured: Day 1 through Day 263 (corresponding to maximum observed duration)
Secondary outcomes (2)
Number of Participants With Complete Response (CR) or Partial Response (PR)
The radiological evaluation based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) was performed by investigator using computed tomography (CT) scan/ magnetic resonance imaging (MRI) scan/ positron emission tomography (PET) scan. The CR was defined as disappearance of all target and non-target lesions and all pathological lymph nodes must have decreased to < 10 mm in short axis. The PR was defined as at least a 30% decrease in the sum of the longest diameters of target lesions taking as reference the baseline sum of longest diameters.
Measured: Day 1 through Day 233
Number of Participants With Antidrug Antibodies (ADAs) Positive to GEN1044
The detection and titer characterization of ADAs was performed using validated, specific, and sensitive electrochemiluminescence immunoassay (ECLIA) methods. Number of participants with ADA positive post baseline to GEN1044 are reported.
Measured: Day 1 through Day 263 (predose on Day 1 of Cycles 1, 2, 3, 5, 7, and then on Day 1 of every 4 cycles thereafter, end of treatment [EOT], and 30 days after last study drug)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2020
- Study start15 Jul 2020
- Primary completion29 Oct 2021
- Study completion29 Oct 2021
Why it stopped: Study was terminated due to MTD was reached
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 Locally Advanced or Metastatic Solid Tumor(s)Studies of the same condition, open and under way.
- More trials run by GenmabThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 48 participants (actual)
Sponsor and investigators
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04424641
- Sponsor's protocol ID
- GCT1044-01
- Other IDs
- 2019-003998-26, MOH_2020-07-26_008713, 2019
- Status last verified
- Jul 2023
- First submitted
- 14 May 2020
- Last updated
- 25 Jul 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Kemper K, Gielen E, Boross P, Houtkamp M, Plantinga TS, de Poot SA, Burm SM, Janmaat ML, Koopman LA, van den Brink EN, Rademaker R, Verzijl D, Engelberts PJ, Satijn D, Sasser AK, Breij EC. Mechanistic and pharmacodynamic studies of DuoBody-CD3x5T4 in preclinical tumor models. Life Sci Alliance. 2022 Sep 8;5(11):e202201481. doi: 10.26508/lsa.202201481. Print 2022 Nov.
PubMed 36271507
Study at a glance
From the registry record, last updated by the sponsor on 25 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- First-in-human, Open-label, Dose-escalation Trial With Expansion Cohorts to Evaluate Safety of GEN1044 in Subjects With Malignant Solid Tumors
- ClinicalTrials.gov ID
- NCT04424641
- Acronym / sponsor ID
- GCT1044-01
- Conditions
- Locally Advanced or Metastatic Solid Tumor(s), Prostate Cancer, Esophageal Cancer, Triple Negative Breast Cancer (TNBC), Squamous Cell Carcinoma of Head and Neck (SCCHN), Non-small Cell Lung Cancer (NSCLC)
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was terminated due to MTD was reached
- Enrolment
- 48 participants (actual)
- Lead sponsor
- GenmabIndustry (pharma, biotech, devices)
- Collaborators
- AbbVie
- Study start
- 15 Jul 2020 (actual)
- Primary completion
- 29 Oct 2021 (actual)
- Study completion
- 29 Oct 2021 (actual)
- First posted
- 11 Jun 2020 (actual)
- Results
- Posted 1 Feb 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the trial is to evaluate the safety, determine the recommended Phase 2 dose (RP2D), and assess preliminary clinical activity of GEN1044 in patients with solid tumors.
Detailed description
The trial is an open-label, multi-center safety trial of GEN1044. The trial consists of two parts: a dose-escalation part (Phase 1) and an expansion part (Phase 2a). The expansion part of the trial will be initiated once the RP2D has been determined from Phase 1.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| GEN1044 | Experimental | Biological: GEN1044 is an immunoglobulin G1 (IgG1) bispecific antibody targeting CD3 and 5T4. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patient with locally advanced or metastatic solid tumor(s) (excluding patients with primary central nervous system [CNS] tumors), who has experienced disease progression while on standard therapy or is intolerant of, or not eligible for, standard therapy.
- Must have an advanced or metastatic, pathologically confirmed diagnosis of one of the following tumors: Uterine Cancer, Prostate Cancer, Esophageal Cancer, TNBC, SCCHN, NSCLC (both adenocarcinoma [ACC] and squamous cell carcinoma [SCC], Bladder Cancer.
- Must sign an informed consent form (ICF) indicating that he or she understands the purpose of, and procedures required for the trial, and is willing to participate in the trial prior to any trial related assessments or procedures.
- Must have measurable disease according to response assessment criteria relevant to the tumor type.
- Must have an Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score of 0-1 at Screening and on C1D1.
Key exclusion criteria (15 listed)
- Has an uncontrolled intercurrent illness, including but not limited to:
- Any history of intracerebral arteriovenous malformation, cerebral aneurysm, new or symptomatic brain metastases or stroke.
- Prior therapy:
- Radiotherapy: Radiotherapy within 14 days prior to first GEN1044 administration. Palliative radiotherapy will be allowed.
- Treatment with an anti-cancer agent (within 28 days or after at least 5 half-lives of the drug, whichever is shorter), prior to GEN1044 administration. Toxicities from previous anti-cancer therapies that have not resolved.
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 |
|---|---|---|
| GEN1044 is an immunoglobulin G1 (IgG1) bispecific antibody targeting CD3 and 5T4.Also: DuoBody®-CD3x5T4GEN1044 will be administered intravenously in cycles of 21 days. | Biological | GEN1044 |
Primary outcome
Number of Participants With Dose Limiting Toxicities (DLTs)
Time frame: From Day 1 to Day 21 of first cycle
The DLT was defined as Grade (G) >= 3 cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome; any G3 or 4 hematologic and non-hematologic toxicity (with exceptions defined by the protocol); laboratory abnormality that required clinically significant medical intervention, led to hospitalization, persisted for >1 week, or resulted in a drug-induced liver injury; G3 or 4 febrile neutropenia; liver toxicity defined by Hy's law; any treatment-related toxicity that caused treatment discontinuation during Cycle 1; or any G5 toxicity.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
Time frame: Day 1 through Day 263 (corresponding to maximum observed duration)
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An serious adverse event (SAE) is defined as an AE that meets one of the following criteria: fatal or life-threatening; results in persistent or significant disability/incapacity; constitutes a congenital anomaly/birth defect; medically significant (an event that jeopardizes the participant or may require medical or surgical intervention to prevent one of the outcomes listed above [medical and scientific judgment must be exercised in deciding whether an AE is 'medically significant']); required inpatient hospitalization or prolongation of existing hospitalization. A TEAE is defined as an AE occurring or worsening between the first dose of GEN1044 and 30 days after the last dose received.
Number of Participants With Abnormal Laboratory Values
Time frame: Day 1 through Day 263 (corresponding to maximum observed duration)
Number of participants with laboratory values of Grade >= 3 by NCI-CTCAE v5.0 are reported. The NCI-CTCAE is a descriptive terminology that is used for gradings (Grade 1-5) of Adverse Events (AEs) and of laboratory values; the latter being summarized here. This table reports laboratory values graded only on the numerical value of the reported parameter and is therefore not graded by symptoms or signs. The abnormal laboratory values assessed by the investigator as being AEs are reported also in the AE table. In case a participant reported multiple severity grades for a laboratory value, only the maximum grade was used.
2 secondary outcomes
Number of Participants With Complete Response (CR) or Partial Response (PR)
Time frame: Day 1 through Day 233
Number of Participants With Antidrug Antibodies (ADAs) Positive to GEN1044
Time frame: Day 1 through Day 263 (predose on Day 1 of Cycles 1, 2, 3, 5, 7, and then on Day 1 of every 4 cycles thereafter, end of treatment [EOT], and 30 days after last study drug)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jul 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 36271507Kemper K, Gielen E, Boross P, Houtkamp M, Plantinga TS, de Poot SA, Burm SM, Janmaat ML, Koopman LA, van den Brink EN, Rademaker R, Verzijl D, Engelberts PJ, Satijn D, Sasser AK, Breij EC. Mechanistic and pharmacodynamic studies of DuoBody-CD3x5T4 in preclinical tumor models. Life Sci Alliance. 2022 Sep 8;5(11):e202201481. doi: 10.26508/lsa.202201481. Print 2022 Nov.
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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.
Roberto Oliveri, MD study director
Genmab
6 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing GEN1044 is an immunoglobulin G1 (IgG1) bispecific antibody targeting CD3 and 5T4. in people with Locally Advanced or Metastatic Solid Tumor(s) and Prostate Cancer, run by Genmab at 6 sites in 4 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 9 inclusion and 15 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: stopped early, as of the sponsor's last update on 25 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States, Spain, Denmark, Israel. 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 1 Feb 2023). 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?
Number of Participants With Dose Limiting Toxicities (DLTs) (time frame: From Day 1 to Day 21 of first cycle). The study lists 3 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 NCT04424641, 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 25 Jul 2023.