HER2 Mutation-Related TumorsPhase 1NCT06253871
A Phase 1/1b Study of IAM1363 in HER2 Cancers
A Phase 1 study testing IAM1363 in people with HER2 Mutation-Related Tumors and HER2, run by Iambic Therapeutics, Inc at 53 sites in 8 countries.
Trial summary
This is a Phase 1/1b open-label, multi-center dose escalation and dose optimization study designed to evaluate the safety and preliminary efficacy of IAM1363 in participants with advanced cancers that harbor HER2 alterations. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HER2 Mutation-Related Tumors, HER2, HER2-positive Breast Cancer
- What is being tested?
- IAM1363
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 383 participants
- Where
- 53 sitesin 8 countries
- Study dates
- 25 Mar 2024to Dec 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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
- Age ≥ 18 years
- Have relapsed/refractory HER2-altered malignancy; for selected cohorts, prospective confirmation of HER2 alteration by central testing is required
- Have progression of disease after the last systemic therapy, or be intolerant of last systemic therapy
- Have radiographically measurable disease by RECIST v1.1 and/or RANO-BM
- Eastern Cooperative Oncology Group (ECOG) performance score 0-1
- Have adequate baseline hematologic, liver and renal function
- Have left ventricular ejection fraction (LVEF) ≥ 50%
- Able to swallow oral medication
Who cannot join
- Clinically significant cardiac disease
- Infection with human immunodeficiency virus (HIV)-1 or HIV-2. Exception: Participants with well-controlled HIV (e.g., CD4 >350/mm3 and undetectable viral load) are eligible
- Current active liver disease including hepatitis A, hepatitis B , or hepatitis C
- Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant small bowel resection that would preclude adequate absorption
- Uncontrolled diabetes
- History of solid organ transplantation
Show all 9Show fewer
- History of Grade ≥2 CNS hemorrhage, or any CNS hemorrhage within 28 days before C1D1
- Prior history of non-infectious interstitial lung disease (ILD). (Exceptions: participants with prior grade 1 ILD that has completely resolved are eligible)
- Participants requiring immediate local therapy for brain metastases
Trial locations and contacts
53 sites in 8 countries. Contact the study team or a site near you to ask about taking part.
53 sites in 8 countries
United States29 sites, 29 recruiting
- Recruiting
University of Michigan
Ann Arbor, Michigan, 48109
- Recruiting
University of Colorado Cancer Center
Aurora, Colorado, 80045
- Recruiting
NEXT Oncology - Austin
Austin, Texas, 78758
- Recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02114
- Recruiting
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
- Recruiting
University of Chicago
Chicago, Illinois, 60637
- Recruiting
University Hospital Cleveland Medical Center
Cleveland, Ohio, 44106
- Recruiting
Cleveland Clinic
Cleveland, Ohio, 44195
- Recruiting
Mary Crowley Cancer Research
Dallas, Texas, 75230
- Recruiting
Henry Ford Cancer Institute
Detroit, Michigan, 48202
- Recruiting
Duke Cancer Institute
Durham, North Carolina, 27710
- Recruiting
NEXT Oncology - Virginia Cancer Specialists
Fairfax, Virginia, 22031
- Recruiting
START - Midwest Cancer Research Center
Grand Rapids, Michigan, 49546
- Recruiting
MD Anderson Cancer Center - University of Texas
Houston, Texas, 77030
- Recruiting
Saint Luke's Cancer Institute
Kansas City, Missouri, 64111
- Recruiting
UCSD Moores Cancer Center
La Jolla, California, 92093
- Recruiting
Dartmouth Hitchcock Medical
Lebanon, New Hampshire, 03756
- Recruiting
USC Norris Comprehensive Cancer Center
Los Angeles, California, 90089
- Recruiting
University of Miami
Miami, Florida, 33136
- Recruiting
SCRI Oncology Partners
Nashville, Tennessee, 37203
- Recruiting
Vanderbilt Ingram Cancer Center
Nashville, Tennessee, 37232
- Recruiting
Rutgers Cancer Institute
New Brunswick, New Jersey, 08901
- Recruiting
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
- Recruiting
OU Health Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104
- Recruiting
Providence Cancer Institute
Portland, Oregon, 97213
- Recruiting
Fred Hutchinson Cancer Center
Seattle, Washington, 98109
- Recruiting
Washington University School of Medicine
St Louis, Missouri, 63110
- Recruiting
Comprehensive Hematology Oncology
St. Petersburg, Florida, 33709
- Recruiting
START Mountain Region
West Valley City, Utah, 84119
hopeteam@startresearch.com
Spain6 sites, 6 recruiting
- Recruiting
Hospital Universitario Vall dHebron
Barcelona, 08035
- Recruiting
Hospital Universitario 12 de Octubre
Madrid, 28041
- Recruiting
START Madrid CIOCC, Hospital Universitario HM Sanchinarro
Madrid, 28050
- Recruiting
Hospital Universitario Regional Málaga
Málaga, 29011
- Recruiting
Hospital Universitario Virgen del Rocio
Seville, 41013
- Recruiting
Hospital Clinico Universitario de Valencia (INCLIVA)
Valencia, 46010
Italy4 sites, 4 recruiting
- Recruiting
Azienda Ospedaliero Universitaria Careggi - Largo Giovanni Alessandro Brambilla 3
Florence, 50134
- Recruiting
Istituto Europeo di Oncologia (IEO)
Milan, 20141
- Recruiting
Grande Ospedale Metropolitano Niguarda
Milan, 20162
- Recruiting
Azienda Ospedaliera Universitaria Luigi Vanvitelli
Naples, 80131
South Korea4 sites, 4 recruiting
- Recruiting
Seoul National University Hospital
Seoul, 03080
- Recruiting
Severance Hospital - Yonsei Cancer Center
Seoul, 03722
- Recruiting
Asan Medical Center
Seoul, 05505
- Recruiting
Samsung Medical Center
Seoul, 06351
France3 sites, 3 recruiting
- Recruiting
Centre Georges François Leclerc
Dijon, 21079
- Recruiting
Institut de Cancerologie de l'Ouest
Saint-Herblain, 44805
- Recruiting
Institut Universitaire du Cancer de Toulouse (IUCT) Oncopole Institut Claudius Regaud "
Toulouse, 31059
Ireland3 sites, 3 recruiting
- Recruiting
Cork University Hospital, Wilton
Cork, T12DC4A
- Recruiting
The START center Dublin
Dublin, Dublin, D07 R2WY
- Recruiting
St. Vincent's University Hospital
Dublin, D04 T6F4
United Kingdom3 sites, 3 recruiting
- Recruiting
Royal Marsden NHS Foundation Trust, Royal Marsden Hospital (RMH)/Chelsea)
Chelsea, SW3 6JJ
- Recruiting
Oxford University Hospitals NHS Foundation Trust Churchill Hospital
Oxford, OX3 7LE
- Recruiting
Royal Marsden NHS Foundation Trust, Royal Marsden Hospital (RMH)/Sutton
Sutton, SM2 5PT
Netherlands1 site, 1 recruiting
- Recruiting
Netherlands Cancer Institute-Antoni van Leeuwenhoek
Amsterdam, 1066CX
About this study
Official title: A Phase 1/1b Study of IAM1363 in Participants With Advanced Cancers Harboring HER2 Alterations
This is a Phase 1/1b open-label, multi-center dose escalation and dose optimization study designed to evaluate the safety and preliminary efficacy of IAM1363 in participants with advanced cancers that harbor HER2 alterations.
Read the detailed description
This is a Phase 1/1b open-label, multi-center study, designed to evaluate IAM1363 in participants with advanced cancers that harbor HER2 alterations.
This study consists of the following 4 parts:
- Part 1 (Monotherapy Dose Escalation)
- Part 2 (Dose Optimization)
- Part 3 (Dose Expansion)
- Part 4 (Combination Cohorts)
Part 1 will enroll participants with a confirmed, relapsed/refractory malignancy with documented diagnosis of HER2 alterations including participants with brain metastases. Once a provisional maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D) has been determined, Part 2 will enroll additional cohorts to optimize dose selection and to further evaluate the safety and preliminary efficacy of IAM1363. Following completion of Dose Optimization, Part 3 will be opened to enroll tumor-specific cohorts utilizing a Simon 2-Stage Minimax Design to evaluate IAM1363 at the selected dose(s).
Part 4 will enroll 4 cohorts of participants who will receive IAM1363 in combination with other anti-cancer agents.
- Conditions
- HER2 Mutation-Related Tumors, HER2, HER2-positive Breast Cancer, HER2 + Breast Cancer, Brain Metastases From Solid Tumors, Brain Metastases From HER2 and Breast Cancer
- Being tested
- IAM1363
- Keywords
- ERBB2 protein, human, Molecular Targeted Therapy, Genes, erbB-2, Receptor, ErbB-2 / antagonists & inhibitors, Neoplasms / drug therapy, HER2 positive, HER2 overexpressing, HER2 altered, Human epidermal growth factor receptor, ErbB Receptors, HER2, brain metastases
- Medical subject headings
- Breast Neoplasms, Carcinoma, Non-Small-Cell Lung, Stomach Neoplasms, Neoplasms, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IAM1363Drug
IAM1363 monotherapy OR IAM1363 in combination with capecitabine + trastuzumab OR IAM1363 in combination with capecitabine + zanidatamab OR IAM1363 in combination with T-Dxd OR IAM1363 in combination with pembrolizumab +/- carboplatin and pemetrexed
| Study group | Role | What they receive |
|---|---|---|
| IAM1363 Monotherapy or Combination Therapy | Experimental | Treatment with IAM1363 capsules, dosed orally alone or in combination with other anti-cancer agents, in 14- or 21-day cycles. Receives: Drug: IAM1363 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence and severity of dose limiting toxicities (DLTs) (Part 1 only)
Incidence and severity of DLTs during the first cycle of treatment in participants in Part 1
Measured: 21 days
Incidence and severity of adverse events (AEs)
Incidence of treatment emergent AEs (TEAEs) and serious adverse events (SAEs)
Measured: Through 30 days after the last dose of study drug
Pharmacokinetic (PK) parameters
PK parameters. Includes but is not limited to assessment of maximum concentration (Cmax).
Measured: Up to 42 days
Confirmed objective response rate (cORR)
Percentage of participants who achieve a confirmed objective response (complete response [CR] + partial response [PR]) per the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1
Measured: Through study completion, estimated as 46 months
Confirmed central nervous system ORR (CNS-cORR)
Percentage of participants who achieve a confirmed CNS-cORR (CNS-CR + CNS-PR) per the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) Criteria
Measured: Through study completion, estimated as 46 months
Frequency of IAM1363 dose modifications, including treatment discontinuations
Measured: Through 30 days after the last dose of study drug
Incidence and severity of clinical laboratory abnormalities
Measured: Through 30 days post last dose of study drug
Incidence of ECG abnormalities
As measured using standard ECG parameters, including pulse rate, QT intervals, and QRS duration.
Measured: Through 30 days after the last dose of study drug
Secondary outcomes (6)
Best overall response (BoR) rate
BoR defined as the best response per RECIST v1.1 and RANO-BM across all assessments
Measured: Through study completion, estimated as 46 months
Duration of response (DoR)
DoR defined as the time between the first confirmed objective response per RECIST v1.1 and RANO-BM and date of disease progression per RECIST v1.1 and RANO-BM or death due to any cause
Measured: Through study completion, estimated as 46 months
Disease control rate (DCR)
DCR defined as the percentage of participants who achieve CR or PR, or stable disease (SD) per RECIST v1.1 and RANO-BM
Measured: Through study completion, estimated as 46 months
Clinical benefit rate (CBR)
CBR defined as the percentage of participants who achieve CR, PR, or SD per RECIST v1.1 and RANO-BM consecutively for 3 months
Measured: Through study completion, estimated as 46 months
Progression-free survival (PFS)
PFS defined as the number of months from the date of first study treatment administration to the earliest of documented progressive disease per RECIST v1.1 and RANO-BM or death without prior progression
Measured: Through study completion, estimated as 46 months
Overall survival (OS)
OS defined as the number of months from the date of first study treatment administration to the date of death, irrespective of cause
Measured: Through study completion, estimated as 46 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2024
- Study start25 Mar 2024
- Primary completionDec 2027 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HER2 Mutation-Related TumorsStudies 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- Dose-escalation and dose optimization
- Masking
- None (open label)
- Enrolment
- 383 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Iambic Therapeutics, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Iambic Therapeutics, Inc., Senior Medical Director, Study director, Iambic Therapeutics, Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06253871
- Sponsor's protocol ID
- IAM1363-01
- Status last verified
- Sep 2026
- First submitted
- 2 Feb 2024
- Last updated
- 9 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/1b Study of IAM1363 in Participants With Advanced Cancers Harboring HER2 Alterations
- ClinicalTrials.gov ID
- NCT06253871
- Acronym / sponsor ID
- IAM1363-01
- Conditions
- HER2 Mutation-Related Tumors, HER2, HER2-positive Breast Cancer, HER2 + Breast Cancer, Brain Metastases From Solid Tumors, Brain Metastases From HER2 and Breast Cancer
- Keywords
- ERBB2 protein, human, Molecular Targeted Therapy, Genes, erbB-2, Receptor, ErbB-2 / antagonists & inhibitors, Neoplasms / drug therapy, HER2 positive, HER2 overexpressing, HER2 altered
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 383 participants (estimated)
- Lead sponsor
- Iambic Therapeutics, IncIndustry (pharma, biotech, devices)
- Study start
- 25 Mar 2024 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 12 Feb 2024 (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 a Phase 1/1b open-label, multi-center dose escalation and dose optimization study designed to evaluate the safety and preliminary efficacy of IAM1363 in participants with advanced cancers that harbor HER2 alterations.
Detailed description
This is a Phase 1/1b open-label, multi-center study, designed to evaluate IAM1363 in participants with advanced cancers that harbor HER2 alterations.
This study consists of the following 4 parts:
- Part 1 (Monotherapy Dose Escalation)
- Part 2 (Dose Optimization)
- Part 3 (Dose Expansion)
- Part 4 (Combination Cohorts)
Part 1 will enroll participants with a confirmed, relapsed/refractory malignancy with documented diagnosis of HER2 alterations including participants with brain metastases. Once a provisional maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D) has been determined, Part 2 will enroll additional cohorts to optimize dose selection and to further evaluate the safety and preliminary efficacy of IAM1363. Following completion of Dose Optimization, Part 3 will be opened to enroll tumor-specific cohorts utilizing a Simon 2-Stage Minimax Design to evaluate IAM1363 at the selected dose(s).
Part 4 will enroll 4 cohorts of participants who will receive IAM1363 in combination with other anti-cancer agents.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Dose-escalation and dose optimization
| Arm | Type | Receives |
|---|---|---|
| IAM1363 Monotherapy or Combination Therapy | Experimental | Drug: IAM1363Treatment with IAM1363 capsules, dosed orally alone or in combination with other anti-cancer agents, in 14- or 21-day cycles. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age ≥ 18 years
- Have relapsed/refractory HER2-altered malignancy; for selected cohorts, prospective confirmation of HER2 alteration by central testing is required
- Have progression of disease after the last systemic therapy, or be intolerant of last systemic therapy
- Have radiographically measurable disease by RECIST v1.1 and/or RANO-BM
- Eastern Cooperative Oncology Group (ECOG) performance score 0-1
Key exclusion criteria (9 listed)
- Clinically significant cardiac disease
- Infection with human immunodeficiency virus (HIV)-1 or HIV-2. Exception: Participants with well-controlled HIV (e.g., CD4 >350/mm3 and undetectable viral load) are eligible
- Current active liver disease including hepatitis A, hepatitis B , or hepatitis C
- Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant small bowel resection that would preclude adequate absorption
- Uncontrolled diabetes
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 |
|---|---|---|
| IAM1363IAM1363 monotherapy OR IAM1363 in combination with capecitabine + trastuzumab OR IAM1363 in combination with capecitabine + zanidatamab OR IAM1363 in combination with T-Dxd OR IAM1363 in combination with pembrolizumab +/- carboplatin and pemetrexed | Drug | IAM1363 Monotherapy or Combination Therapy |
Primary outcome
Incidence and severity of dose limiting toxicities (DLTs) (Part 1 only)
Time frame: 21 days
Incidence and severity of DLTs during the first cycle of treatment in participants in Part 1
Incidence and severity of adverse events (AEs)
Time frame: Through 30 days after the last dose of study drug
Incidence of treatment emergent AEs (TEAEs) and serious adverse events (SAEs)
Pharmacokinetic (PK) parameters
Time frame: Up to 42 days
PK parameters. Includes but is not limited to assessment of maximum concentration (Cmax).
Confirmed objective response rate (cORR)
Time frame: Through study completion, estimated as 46 months
Percentage of participants who achieve a confirmed objective response (complete response [CR] + partial response [PR]) per the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1
Confirmed central nervous system ORR (CNS-cORR)
Time frame: Through study completion, estimated as 46 months
Percentage of participants who achieve a confirmed CNS-cORR (CNS-CR + CNS-PR) per the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) Criteria
Frequency of IAM1363 dose modifications, including treatment discontinuations
Time frame: Through 30 days after the last dose of study drug
Incidence and severity of clinical laboratory abnormalities
Time frame: Through 30 days post last dose of study drug
Incidence of ECG abnormalities
Time frame: Through 30 days after the last dose of study drug
As measured using standard ECG parameters, including pulse rate, QT intervals, and QRS duration.
6 secondary outcomes
Best overall response (BoR) rate
Time frame: Through study completion, estimated as 46 months
Duration of response (DoR)
Time frame: Through study completion, estimated as 46 months
Disease control rate (DCR)
Time frame: Through study completion, estimated as 46 months
Clinical benefit rate (CBR)
Time frame: Through study completion, estimated as 46 months
Progression-free survival (PFS)
Time frame: Through study completion, estimated as 46 months
Overall survival (OS)
Time frame: Through study completion, estimated as 46 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2026.
Related trials for HER2 Mutation-Related Tumors
Active, not recruitingObservational study
Distribution of the Homologous Recombination-related (HRR) Genesmutationsand HRD in Breast Cancer
Breast Cancer, HER2-low Breast Cancer
Active, not recruitingPhase 2
To Assess Safety and Efficacy of Agents Targeting DNA Damage Repair With Olaparib Versus Olaparib Monotherapy.
Metastatic Triple Negative Breast Cancer
RecruitingPhase 1
Open-Label Study of BBO-10203 in Subjects With Advanced Solid Tumors
Solid Tumor, Adult, Metastatic Breast Cancer
RecruitingPhase 1/2
PRE-ISPY Phase I/II Oncology Platform Program
HER2-positive Breast Cancer, Metastatic Cancer
Enrolling by invitationObservational study
Integrated Genomics in Oncogene-driven NSCLC With Acquired Resistance
Oncogene-addicted Non Small Cell Lung Cancer, EGFR Mutation
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.
Iambic Therapeutics, Inc., Senior Medical Director study director
Iambic Therapeutics, Inc
53 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing IAM1363 in people with HER2 Mutation-Related Tumors and HER2, run by Iambic Therapeutics, Inc at 53 sites in 8 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: looking for participants now, as of the sponsor's last update on 9 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 53 sites in United States, Spain, Italy, South Korea, France and 3 more countries. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Iambic Therapeutics, Inc., Senior Medical Director (619-330-5499, ClinicalTrials@Iambic.ai), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence and severity of dose limiting toxicities (DLTs) (Part 1 only) (time frame: 21 days). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Sep 2026.