Advanced Solid Tumors CancerPhase 1NCT03145909
A Study Evaluating the Safety, Pharmacokinetics and Anti-Tumor Activity of ABBV-176 in Subjects With Advanced Solid Tumors Likely to Express Prolactin Receptor (PRLR)
A Phase 1 study testing ABBV-176 in people with Advanced Solid Tumors Cancer, run by AbbVie at 11 sites in 4 countries.
Trial summary
This is an open-label, Phase I, dose-escalation study to determine the maximum tolerated dose (MTD) and the recommended phase two dose (RPTD), and to assess the safety, preliminary efficacy, and pharmacokinetic (PK) profile of ABBV-176 for participants with advanced solid tumors likely to express Prolactin Receptor… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumors Cancer
- What is being tested?
- ABBV-176
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 11 sitesin 4 countries
- Study dates
- 3 Jul 2017to 27 Nov 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Participant has histological confirmation of a locally advanced or metastatic solid tumor of a type associated with Prolactin Receptor (PRLR) expression that has progressed on prior treatment, is not amenable to treatment with curative intent, and has no other therapy options known to provide clinical benefit or the subject is ineligible for such therapies.
- Dose Escalation Cohort: must have breast cancer, colorectal cancer, adrenocortical carcinoma, chromophobe renal cell carcinoma.
- Expanded Cohort: must have breast cancer.
- Participant must consent to provide the following for biomarker analyses:
- Dose Escalation Cohort: archived tumor tissue or fresh tumor biopsy.
- Expanded Cohort: archived tumor tissue and fresh tumor biopsy.
- Participant has Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
- Participant has adequate bone marrow, renal, and hepatic function.
Who cannot join
- Participant received anticancer therapy including chemotherapy, immunotherapy, radiotherapy, biologic, or any investigational therapy within 21 days before Study Day 1; participant received palliative radiotherapy or small molecule targeted anti-cancer agents within 14 days of Study Day 1.
- Participant has prior exposure to any pyrrolobenzodiazopine-containing agent
- Participant has unresolved, clinically significant toxicities from prior anticancer therapy, defined as greater than Grade 1 on Common Terminology for adverse events.
- Participant has clinically significant uncontrolled conditions.
- Participant has a history of major immunologic reaction to any Immunoglobulin G (IgG).
- Participant has received more than 4 prior lines of systemic cytotoxic therapy (not including neo-adjuvant or adjuvant therapy).
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- For prior cytotoxic therapy, treatment for 1 full cycle or less will not be considered as prior therapy unless the patient experienced progression of disease while on that therapy.
- Participant has a history of >= grade 3 AST, ALT, or bilirubin increase or has extensive liver resection (i.e., left lobe resection).
- Participant has a history of cholecystitis (subject with history of cholecystectomy will not be excluded), or has active gallbladder disease.
Trial locations and contacts
11 sites in 4 countries.
11 sites in 4 countries
United States7 sites
City of Hope /ID# 161079
Duarte, California, 91010
St. Lukes Cancer Institute /ID# 201353
Kansas City, Missouri, 64111-5905
Rutgers Cancer Institute of NJ /ID# 161080
New Brunswick, New Jersey, 08903
Yale University /ID# 201357
New Haven, Connecticut, 06510
University of Utah /ID# 161606
Salt Lake City, Utah, 84112-5500
HonorHealth Research Institute - Pima /ID# 161078
Scottsdale, Arizona, 85258-2345
Washington University-School of Medicine /ID# 162745
St Louis, Missouri, 63110
Australia2 sites
Sydney Children's Hospital /ID# 162917
Randwick, New South Wales, 2031
Mater Misericordiae /ID# 162918
South Brisbane, Queensland, 4101
About this study
Official title: A Phase 1 Study Evaluating the Safety, Pharmacokinetics and Anti-Tumor Activity of ABBV-176 in Subjects With Advanced Solid Tumors Likely to Express Prolactin Receptor (PRLR)
This is an open-label, Phase I, dose-escalation study to determine the maximum tolerated dose (MTD) and the recommended phase two dose (RPTD), and to assess the safety, preliminary efficacy, and pharmacokinetic (PK) profile of ABBV-176 for participants with advanced solid tumors likely to express Prolactin Receptor (PRLR). The study will consist of 2 cohorts: Dose Escalation and Expanded Recommended Phase 2 Dose.
- Conditions
- Advanced Solid Tumors Cancer
- Being tested
- ABBV-176
- Keywords
- Cancer, Metastatic, Prolactin Receptor (PRLR), Breast cancer, Colorectal cancer, Adrenocortical carcinoma,, Chromophobe renal cell carcinoma, Hepatocellular carcinoma
- Medical subject headings
- Neoplasms, Neoplasm Metastasis, Breast Neoplasms, Colorectal Neoplasms, Adrenocortical Carcinoma, Carcinoma, Renal Cell, Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ABBV-176Drug
Intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation Cohort | Experimental | ABBV-176 will be administered via intravenous infusion at escalating dose levels until the maximum tolerated dose is reached. Receives: Drug: ABBV-176 |
| Expanded RPTD Cohort | Experimental | ABBV-176 via intravenous administration in participants with breast cancer at the Recommended Phase Two Dose (RPTD) determined during the Dose Escalation Cohort Receives: Drug: ABBV-176 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Escalation Cohort: Tmax of ABBV-176
Time to Cmax (Tmax) of ABBV-176
Measured: Up to approximately 57 days
Dose Escalation Cohort: AUC∞ for ABBV-176
AUC∞ is the area under the plasma concentration-time curve from Time 0 to infinite time.
Measured: Up to approximately 57 days
Dose Escalation Cohort: Terminal phase elimination rate constant (β) for ABBV-176
Terminal phase elimination rate constant (β)
Measured: Up to approximately 57 days
Dose Escalation Cohort: Recommended Phase 2 dose (RPTD) for ABBV-176
The RPTD will be determined using available safety and pharmacokinetics data upon completion of the Dose Escalation Cohort.
Measured: Minimum first cycle of dosing (up to 21 days)
Dose Escalation Cohort: Cmax of ABBV-176
Maximum observed plasma concentration (Cmax) of ABBV-176.
Measured: Up to approximately 57 days
Dose Escalation Cohort: Maximum tolerated dose (MTD) of ABBV-176
MTD will be defined as the highest dose level at which less than or equal to 33% of participants experience a dose limiting toxicity.
Measured: Minimum first cycle of dosing (up to 21 days)
Expanded Recommended Phase Two Dose (RPTD) Cohort: Objective Response Rate (ORR)
ORR is defined as the proportion of participants with a response of partial response (PR) or better per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.
Measured: Up to approximately 2 years
Dose Escalation Cohort: AUCt for ABBV-176
Area Under the Plasma Concentration-time Curve from Time 0 to the Time of the Last Measurable Concentration (AUCt) for ABBV-176.
Measured: Up to approximately 57 days
Dose Escalation Cohort: t1/2 for ABBV-176
Terminal elimination half-life (t1/2)
Measured: Up to approximately 57 days
Secondary outcomes (11)
Expanded RPTD Cohort: AUCt for ABBV-176
Area Under the Plasma Concentration-time Curve from Time 0 to the Time of the Last Measurable Concentration (AUCt)
Measured: Up to approximately 15 days
Expanded RPTD Cohort: Tmax of ABBV-176
Time to Cmax (Tmax) of ABBV-176
Measured: Up to approximately 15 days
Expanded RPTD Cohort: Overall Survival (OS)
OS is defined as number of days from the date of the first dose to the date of death for all dosed subjects. For subjects who are not deceased, the data will be censored at the date of the last study visit, or the last know date to be alive, whichever is later.
Measured: Up to 2 years after the last dose of study drug
Expanded RPTD Cohort: Cmax of ABBV-176
Maximum observed plasma concentration (Cmax) of ABBV-176.
Measured: Up to approximately 15 days
Expanded RPTD Cohort: Duration of Response (DOR)
DOR is defined as the time from the date of the participant's documented first response of PR or better to the date of documented disease progression or death due to the disease, whichever occurs first.
Measured: Up to approximately 2 years
Expanded RPTD Cohort: Terminal phase elimination rate constant (β) for ABBV-176
Terminal phase elimination rate constant (β) for ABBV-176
Measured: Up to approximately 15 days
Expanded Recommended Phase Two Dose (RPTD) Cohort: Progression-Free Survival (PFS)
PFS is defined as the time from the participant's first dose of study drug (Day 1) to the date of documented disease progression (per RECIST 1.1), or death due to any cause, whichever occurs first.
Measured: Up to approximately 2 years
Expanded RPTD Cohort: Change in ECOG Performance Status
Change from baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status
Measured: Up to approximately 2 years
Expanded RPTD Cohort: AUC∞ for ABBV-176
Area Under the Plasma Concentration-time Curve from Time 0 to infinite time (AUC∞)
Measured: Up to approximately 15 days
Expanded RPTD Cohort: t1/2 for ABBV-176
Terminal elimination half-life (t1/2) for ABBV-176
Measured: Up to approximately 15 days
Dose Escalation Cohort: Change from Baseline in QTcF
QT interval measurement corrected by Fridericia's formula (QTcF) mean change from baseline
Measured: Up to approximately 47 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2017
- Study start3 Jul 2017
- Primary completion27 Nov 2018
- Study completion27 Nov 2018
Why it stopped: Safety
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced Solid Tumors CancerStudies of the same condition, open and under way.
- More trials run by AbbVieThe 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- AbbVie
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- AbbVie Inc., Study director, AbbVie
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03145909
- Sponsor's protocol ID
- M15-916
- Other IDs
- 2016-004597-18, 2016
- Status last verified
- Nov 2018
- First submitted
- 5 May 2017
- Last updated
- 29 Nov 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Lemech C, Woodward N, Chan N, Mortimer J, Naumovski L, Nuthalapati S, Tong B, Jiang F, Ansell P, Ratajczak CK, Sachdev J. A first-in-human, phase 1, dose-escalation study of ABBV-176, an antibody-drug conjugate targeting the prolactin receptor, in patients with advanced solid tumors. Invest New Drugs. 2020 Dec;38(6):1815-1825. doi: 10.1007/s10637-020-00960-z. Epub 2020 Jun 10.
PubMed 32524319
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study Evaluating the Safety, Pharmacokinetics and Anti-Tumor Activity of ABBV-176 in Subjects With Advanced Solid Tumors Likely to Express Prolactin Receptor (PRLR)
- ClinicalTrials.gov ID
- NCT03145909
- Acronym / sponsor ID
- M15-916
- Conditions
- Advanced Solid Tumors Cancer
- Keywords
- Cancer, Metastatic, Prolactin Receptor (PRLR), Breast cancer, Colorectal cancer, Adrenocortical carcinoma,, Chromophobe renal cell carcinoma, Hepatocellular carcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Safety
- Enrolment
- 19 participants (actual)
- Lead sponsor
- AbbVieIndustry (pharma, biotech, devices)
- Study start
- 3 Jul 2017 (actual)
- Primary completion
- 27 Nov 2018 (actual)
- Study completion
- 27 Nov 2018 (actual)
- First posted
- 9 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open-label, Phase I, dose-escalation study to determine the maximum tolerated dose (MTD) and the recommended phase two dose (RPTD), and to assess the safety, preliminary efficacy, and pharmacokinetic (PK) profile of ABBV-176 for participants with advanced solid tumors likely to express Prolactin Receptor (PRLR). The study will consist of 2 cohorts: Dose Escalation and Expanded Recommended Phase 2 Dose.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation Cohort | Experimental | Drug: ABBV-176ABBV-176 will be administered via intravenous infusion at escalating dose levels until the maximum tolerated dose is reached. |
| Expanded RPTD Cohort | Experimental | Drug: ABBV-176ABBV-176 via intravenous administration in participants with breast cancer at the Recommended Phase Two Dose (RPTD) determined during the Dose Escalation Cohort |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Participant has histological confirmation of a locally advanced or metastatic solid tumor of a type associated with Prolactin Receptor (PRLR) expression that has progressed on prior treatment, is not amenable to treatment with curative intent, and has no other therapy options known to provide clinical benefit or the subject is ineligible for such therapies.
- Dose Escalation Cohort: must have breast cancer, colorectal cancer, adrenocortical carcinoma, chromophobe renal cell carcinoma.
- Expanded Cohort: must have breast cancer.
- Participant must consent to provide the following for biomarker analyses:
- Dose Escalation Cohort: archived tumor tissue or fresh tumor biopsy.
Key exclusion criteria (9 listed)
- Participant received anticancer therapy including chemotherapy, immunotherapy, radiotherapy, biologic, or any investigational therapy within 21 days before Study Day 1; participant received palliative radiotherapy or small molecule targeted anti-cancer agents within 14 days of Study Day 1.
- Participant has prior exposure to any pyrrolobenzodiazopine-containing agent
- Participant has unresolved, clinically significant toxicities from prior anticancer therapy, defined as greater than Grade 1 on Common Terminology for adverse events.
- Participant has clinically significant uncontrolled conditions.
- Participant has a history of major immunologic reaction to any Immunoglobulin G (IgG).
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 |
|---|---|---|
| ABBV-176Intravenous infusion | Drug | Dose Escalation Cohort, Expanded RPTD Cohort |
Primary outcome
Dose Escalation Cohort: Tmax of ABBV-176
Time frame: Up to approximately 57 days
Time to Cmax (Tmax) of ABBV-176
Dose Escalation Cohort: AUC∞ for ABBV-176
Time frame: Up to approximately 57 days
AUC∞ is the area under the plasma concentration-time curve from Time 0 to infinite time.
Dose Escalation Cohort: Terminal phase elimination rate constant (β) for ABBV-176
Time frame: Up to approximately 57 days
Terminal phase elimination rate constant (β)
Dose Escalation Cohort: Recommended Phase 2 dose (RPTD) for ABBV-176
Time frame: Minimum first cycle of dosing (up to 21 days)
The RPTD will be determined using available safety and pharmacokinetics data upon completion of the Dose Escalation Cohort.
Dose Escalation Cohort: Cmax of ABBV-176
Time frame: Up to approximately 57 days
Maximum observed plasma concentration (Cmax) of ABBV-176.
Dose Escalation Cohort: Maximum tolerated dose (MTD) of ABBV-176
Time frame: Minimum first cycle of dosing (up to 21 days)
MTD will be defined as the highest dose level at which less than or equal to 33% of participants experience a dose limiting toxicity.
Expanded Recommended Phase Two Dose (RPTD) Cohort: Objective Response Rate (ORR)
Time frame: Up to approximately 2 years
ORR is defined as the proportion of participants with a response of partial response (PR) or better per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.
Dose Escalation Cohort: AUCt for ABBV-176
Time frame: Up to approximately 57 days
Area Under the Plasma Concentration-time Curve from Time 0 to the Time of the Last Measurable Concentration (AUCt) for ABBV-176.
Dose Escalation Cohort: t1/2 for ABBV-176
Time frame: Up to approximately 57 days
Terminal elimination half-life (t1/2)
11 secondary outcomes
Expanded RPTD Cohort: AUCt for ABBV-176
Time frame: Up to approximately 15 days
Expanded RPTD Cohort: Tmax of ABBV-176
Time frame: Up to approximately 15 days
Expanded RPTD Cohort: Overall Survival (OS)
Time frame: Up to 2 years after the last dose of study drug
Expanded RPTD Cohort: Cmax of ABBV-176
Time frame: Up to approximately 15 days
Expanded RPTD Cohort: Duration of Response (DOR)
Time frame: Up to approximately 2 years
Expanded RPTD Cohort: Terminal phase elimination rate constant (β) for ABBV-176
Time frame: Up to approximately 15 days
Expanded Recommended Phase Two Dose (RPTD) Cohort: Progression-Free Survival (PFS)
Time frame: Up to approximately 2 years
Expanded RPTD Cohort: Change in ECOG Performance Status
Time frame: Up to approximately 2 years
Expanded RPTD Cohort: AUC∞ for ABBV-176
Time frame: Up to approximately 15 days
Expanded RPTD Cohort: t1/2 for ABBV-176
Time frame: Up to approximately 15 days
Dose Escalation Cohort: Change from Baseline in QTcF
Time frame: Up to approximately 47 days
Results and safety
The study was stopped early (reason given: Safety). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Nov 2018.
- Derived from this study: PubMed 32524319Lemech C, Woodward N, Chan N, Mortimer J, Naumovski L, Nuthalapati S, Tong B, Jiang F, Ansell P, Ratajczak CK, Sachdev J. A first-in-human, phase 1, dose-escalation study of ABBV-176, an antibody-drug conjugate targeting the prolactin receptor, in patients with advanced solid tumors. Invest New Drugs. 2020 Dec;38(6):1815-1825. doi: 10.1007/s10637-020-00960-z. Epub 2020 Jun 10.
- Individual participant dataSharing planned: Undecided
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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.
AbbVie Inc. study director
AbbVie
11 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ABBV-176 in people with Advanced Solid Tumors Cancer, run by AbbVie at 11 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 8 inclusion and 9 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 29 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States, Australia, Denmark, Spain. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Safety). Results are not available in the source record.
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?
Dose Escalation Cohort: Tmax of ABBV-176 (time frame: Up to approximately 57 days). The study lists 9 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 NCT03145909, 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 29 Nov 2018.