A Phase 1 interventional study of MEN1611 and Trastuzumab in Advanced or Metastatic Breast Cancer, sponsored by Menarini Group. Completed at 27 sites in 6 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-06-26.
Sponsored by Menarini Group · Phase 1, Interventional, and Treatment
The main purpose of this open-label, dose-escalation, phase Ib study is to identify the appropriate dose of MEN1611 to be used in combination with Trastuzumab with/without Fulvestrant for the treatment of advanced or metastatic HER2-positive breast cancer
This Phase Ib study will investigate the safety and anti-tumor activity of daily oral doses MEN1611 in combination with Trastuzumab with/without Fulvestrant in female and male patients affected by advanced or metastatic HER2-positive breast cancer. Fulvestrant will be added to the post-menopausal patients with hormone-sensitive disease.
MEN1611 is an investigational drug which blocks a protein called PI3K (phosphoinositide 3-kinase) involved in cancer cells growth. The Maximum Tolerated Dose (MTD) of MEN1611 given as single agent was assessed in a phase I trial in patients with advanced solid tumors.
This Phase IB will start with a dose escalation part (Step 1) to identify the MTD of MEN1611 given in combination with Trastuzumab with/without Fulvestrant.
The study will continue with a cohort expansion (Step 2) to investigate the anti-tumor activity of the selected MEN1611 dose level considered to be tolerable by a Safety Review Committee.
14,825 studies on the registry are indexed under Breast Neoplasms; 3,319 are open to participants now.
This study's enrollment of 62 is below the median of 72 across 10,896 interventional studies indexed under Breast Neoplasms.
Browse Breast Neoplasms studies →Menarini Group is the lead sponsor of 28 studies on the registry; 1 is open to participants now.
Counted across the registry records on this site, refreshed daily.
Main Inclusion Criteria:
Main Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
HER2 is a protein, made from the ERBB2 gene, that drives the growth of some cancers. A study may look for a level of the protein, extra copies of the gene, or a particular change in it.
In breast cancer, protein tests are read as HER2-positive, HER2-low or HER2-negative; other cancers use their own rules. Check which test result the study requires.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HER2
HER2 is a protein, made from the ERBB2 gene, that drives the growth of some cancers. A study may look for a level of the protein, extra copies of the gene, or a particular change in it.
In breast cancer, protein tests are read as HER2-positive, HER2-low or HER2-negative; other cancers use their own rules. Check which test result the study requires.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Brain metastases
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HbA1c
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
MEN1611 + Trastuzumab +/- Fulvestrant
Drug: MEN1611 · Drug: Trastuzumab · Drug: Fulvestrant
MEN1611 oral dose administered twice daily for a continuous 28-day cycle
Trastuzumab solution for infusion administered weekly via IV
Fulvestrant solution for injection administered monthly via IM (only for HR-positive postmenopausal women)
MTD of MEN1611 in Combination With Trastuzumab ± Fulvestrant
MTD was defined as the highest dose level at which no more than 1 participant experienced a DLT during the 28-day DLT assessment window.
Time frame: Up to 28 Days
Number of Participants With DLTs of MEN1611 in Combination With Trastuzumab ± Fulvestrant
DLT was defined as the occurrence of any of the protocol defined adverse drug reactions (ADRs) related to the combination regimens or to MEN1611 alone and unrelated to the participants' underlying disease or concomitant medication occurring during 28 days after the first MEN1611 administration.
Time frame: Up to 28 days
RP2D of MEN1611 in Combination With Trastuzumab ± Fulvestrant
RP2D was defined as the highest dose level in milligrams (mg) at which no more than 1 participant experienced a DLT during the DLT assessment window (28days), or the maximum dose judged to be tolerable.
Time frame: Up to 28 days
Best Overall Response (BOR) of MEN1611 in Combination With Trastuzumab ± Fulvestrant
BOR was defined as percentage of participants who had a best overall response to therapy of complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) and was defined according to Response Evaluation Criteria in Solid Tumors version 1.1 assessment locally performed using computed tomography scans or magnetic resonance imaging of the chest and abdomen (including pelvis and adrenal glands).
Time frame: Up to 3 years
Objective Response Rate (ORR) of MEN1611 in Combination With Trastuzumab ± Fulvestrant
ORR was calculated as the sum of the Best Overall Response (BOR) of complete response (CR) and partial response (PR) rates. ORR was defined according to Response Evaluation Criteria in Solid Tumors version 1.1assessment performed using computed tomography scans or magnetic resonance imaging of the chest and abdomen (including pelvis and adrenal glands).
Time frame: Up to 3 years
Disease Control Rate (DCR) of MEN1611 in Combination With Trastuzumab ± Fulvestrant
DCR was defined as percentage of participants whose disease shrank or remained stable over a certain time period and was calculated as the sum of the best overall response (BOR) rates of CR, PR and Stable Disease (SD) rates.
Time frame: Up to 3 years
Duration of Response (DOR) of MEN1611 in Combination With Trastuzumab ± Fulvestrant
DOR was defined as time from first occurrence of a BOR of PR, CR or SD as locally assessed, until the disease has been shown to progress following treatment. Participants with a previous response who did not show a relapse or die without recording a relapse were censored at their last available relapse-free tumour assessment date. Participants with only one tumour assessment after baseline showing progressive disease (PD) were not included in the calculation.
Time frame: Up to 3 years
Progression-free Survival (PFS) of MEN1611 in Combination With Trastuzumab ± Fulvestrant
PFS was defined as the number of days between the first study treatment administration to the date of first documented disease progression as per local assessment, relapse or death from any cause. Responding participants and participants who were lost to follow-up were censored at their last tumour assessment date.
Time frame: Up to 3 years
Overall Survival (OS) of MEN1611 in Combination With Trastuzumab ± Fulvestrant
OS was defined as the number of days between the first study treatment administration and death from any cause. Participants still alive who had withdrawn from the study were censored using the latest among end of study and follow-up dates. Drop-out participants were considered censored and the last available date in which the participant was known to be alive were used for calculation.
Time frame: Up to 3 years
A total of 73 participants were screened for study eligibility, of which 11 were considered as screen failures.
| Milestone | Dose Escalation Cohort 1 | Dose Escalation Cohort 2 | Dose Expansion Cohort |
|---|---|---|---|
| Started | 3 | 3 | 56 |
| Received at least 1 dose of study drug | 3 | 3 | 56 |
| Dlt population | 3 | 3 | 3 |
| Completed | 0 | 0 | 23 |
| Not completed | 3 | 3 | 33 |
| Withdrew: Physician decision | 1 | 1 | 0 |
| Withdrew: Withdrawal by subject | 0 | 0 | 6 |
| Withdrew: Participant excluded from efficacy population | 0 | 0 | 1 |
| Withdrew: Death | 0 | 0 | 2 |
| Withdrew: Progressive disease | 2 | 2 | 2 |
| Withdrew: Disease progression needing additional medication | 0 | 0 | 17 |
| Withdrew: Sponsor decision | 0 | 0 | 2 |
| Withdrew: Other medical reasons | 0 | 0 | 3 |
MTD was defined as the highest dose level at which no more than 1 participant experienced a DLT during the 28-day DLT assessment window.
| milligrams (mg) | Dose Escalation Cohorts 1 and 2, and Dose Expansion Cohort |
|---|---|
| MTD of MEN1611 in Combination With Trastuzumab ± Fulvestrant | 48 |
DLT was defined as the occurrence of any of the protocol defined adverse drug reactions (ADRs) related to the combination regimens or to MEN1611 alone and unrelated to the participants' underlying disease or concomitant medication occurring during 28 days after the first MEN1611 administration.
| Participants | Dose Escalation Cohort 1 | Dose Escalation Cohort 2 | Dose Escalation Cohort 3 |
|---|---|---|---|
| Number of Participants With DLTs of MEN1611 in Combination With Trastuzumab ± Fulvestrant | 0 | 0 | 0 |
RP2D was defined as the highest dose level in milligrams (mg) at which no more than 1 participant experienced a DLT during the DLT assessment window (28days), or the maximum dose judged to be tolerable.
| mg | Dose Escalation Cohorts 1 and 2, and Dose Expansion Cohort |
|---|---|
| RP2D of MEN1611 in Combination With Trastuzumab ± Fulvestrant | 48 |
BOR was defined as percentage of participants who had a best overall response to therapy of complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) and was defined according to Response Evaluation Criteria in Solid Tumors version 1.1 assessment locally performed using computed tomography scans or magnetic resonance imaging of the chest and abdomen (including pelvis and adrenal glands).
| percentage of participants | Dose Escalation Cohort 1 | Dose Escalation Cohort 2 | Dose Expansion Cohort |
|---|---|---|---|
| Complete Response (CR) | 0 | 0 | 4.8 |
| Partial Response (PR) | 0 | 66.7 | 35.7 |
| Stable Disease (SD) | 33.3 | 33.3 | 47.6 |
| Non-CR/Non-PD | 0 | 0 | 0 |
| Progressive Disease (PD) | 66.7 | 0 | 9.5 |
| Not Evaluable (NE) | 0 | 0 | 2.4 |
ORR was calculated as the sum of the Best Overall Response (BOR) of complete response (CR) and partial response (PR) rates. ORR was defined according to Response Evaluation Criteria in Solid Tumors version 1.1assessment performed using computed tomography scans or magnetic resonance imaging of the chest and abdomen (including pelvis and adrenal glands).
| percentage of participants | Dose Escalation Cohort 1 | Dose Escalation Cohort 2 | Dose Expansion Cohort |
|---|---|---|---|
| Objective Response Rate (ORR) of MEN1611 in Combination With Trastuzumab ± Fulvestrant | 0 (0 to 70.8) | 66.7 (9.4 to 99.2) | 40.5 (25.6 to 56.7) |
DCR was defined as percentage of participants whose disease shrank or remained stable over a certain time period and was calculated as the sum of the best overall response (BOR) rates of CR, PR and Stable Disease (SD) rates.
| percentage of participants | Dose Escalation Cohort 1 | Dose Escalation Cohort 2 | Dose Expansion Cohort |
|---|---|---|---|
| Disease Control Rate (DCR) of MEN1611 in Combination With Trastuzumab ± Fulvestrant | 33.3 (0.8 to 90.6) | 100 (29.2 to 100) | 88.1 (74.4 to 96) |
DOR was defined as time from first occurrence of a BOR of PR, CR or SD as locally assessed, until the disease has been shown to progress following treatment. Participants with a previous response who did not show a relapse or die without recording a relapse were censored at their last available relapse-free tumour assessment date. Participants with only one tumour assessment after baseline showing progressive disease (PD) were not included in the calculation.
| days | Dose Escalation Cohort 1 | Dose Escalation Cohort 2 | Dose Expansion Cohort |
|---|---|---|---|
| Duration of Response (DOR) of MEN1611 in Combination With Trastuzumab ± Fulvestrant | 224 (0 to NA) | NA (29 to NA) | 114 (65 to 244) |
PFS was defined as the number of days between the first study treatment administration to the date of first documented disease progression as per local assessment, relapse or death from any cause. Responding participants and participants who were lost to follow-up were censored at their last tumour assessment date.
| days | Dose Escalation Cohort 1 | Dose Escalation Cohort 2 | Dose Expansion Cohort |
|---|---|---|---|
| Progression-free Survival (PFS) of MEN1611 in Combination With Trastuzumab ± Fulvestrant | 62 (53 to NA) | 203 (106 to NA) | 167 (116 to 217) |
OS was defined as the number of days between the first study treatment administration and death from any cause. Participants still alive who had withdrawn from the study were censored using the latest among end of study and follow-up dates. Drop-out participants were considered censored and the last available date in which the participant was known to be alive were used for calculation.
| days | Dose Escalation Cohort 1 | Dose Escalation Cohort 2 | Dose Expansion Cohort |
|---|---|---|---|
| Overall Survival (OS) of MEN1611 in Combination With Trastuzumab ± Fulvestrant | 120 (112 to NA) | 203 (143 to NA) | 989 (513 to NA) |
Collected over Up to approximately 3 years. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Dose Escalation Cohort 1 | 3/3 (100%) | 2/3 (66.7%) | 2/3 (66.7%) |
| Dose Escalation Cohort 2 | 3/3 (100%) | 3/3 (100%) | 3/3 (100%) |
| Dose Expansion Cohort | 28/56 (50%) | 21/56 (37.5%) | 56/56 (100%) |
| Event | Dose Escalation Cohort 1 | Dose Escalation Cohort 2 | Dose Expansion Cohort |
|---|---|---|---|
| Ileus paralyticGastrointestinal disorders | 0/3 | 1/3 | 0/56 |
| Rib fractureInjury, poisoning and procedural complications | 0/3 | 1/3 | 0/56 |
| HyperglycaemiaMetabolism and nutrition disorders | 1/3 | 0/3 | 5/56 |
| Bone painMusculoskeletal and connective tissue disorders | 1/3 | 0/3 | 0/56 |
| PneumonitisRespiratory, thoracic and mediastinal disorders | 0/3 | 1/3 | 0/56 |
| Pain of skinSkin and subcutaneous tissue disorders | 1/3 | 0/3 | 0/56 |
| DiarrhoeaGastrointestinal disorders | 0/3 | 0/3 | 3/56 |
| Device related infectionInfections and infestations | 0/3 | 0/3 | 2/56 |
| AnaemiaBlood and lymphatic system disorders | 0/3 | 0/3 | 1/56 |
| HaematemesisGastrointestinal disorders | 0/3 | 0/3 | 1/56 |
| Event | Dose Escalation Cohort 1 | Dose Escalation Cohort 2 | Dose Expansion Cohort |
|---|---|---|---|
| AstheniaGeneral disorders | 1/3 | 3/3 | 15/56 |
| AnaemiaBlood and lymphatic system disorders | 2/3 | 1/3 | 18/56 |
| DiarrhoeaGastrointestinal disorders | 2/3 | 2/3 | 36/56 |
| NauseaGastrointestinal disorders | 2/3 | 0/3 | 26/56 |
| Aspartate aminotransferase increasedInvestigations | 0/3 | 2/3 | 12/56 |
| Decreased appetiteMetabolism and nutrition disorders | 1/3 | 2/3 | 14/56 |
| Vulvovaginal pruritusReproductive system and breast disorders | 0/3 | 2/3 | 0/56 |
| PruritusSkin and subcutaneous tissue disorders | 0/3 | 2/3 | 6/56 |
| HyperglycaemiaMetabolism and nutrition disorders | 1/3 | 1/3 | 21/56 |
| XerophthalmiaCardiac disorders | 0/3 | 1/3 | 0/56 |
Safety population included all participants who received at least 1 dose of MEN1611.
| Age, Categorical(Participants) | Dose Escalation Cohort 1 | Dose Escalation Cohort 2 | Dose Expansion Cohort | Total |
|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 1 | 2 | 43 | 46 |
| >=65 years | 2 | 1 | 13 | 16 |
| Age, Continuous(years) | Dose Escalation Cohort 1 | Dose Escalation Cohort 2 | Dose Expansion Cohort | Total |
|---|---|---|---|---|
| Mean | 65 ± 7.937 | 59.33 ± 14.468 | 53.36 ± 11.112 | 56.02 ± 55.50 |
| Sex: Female, Male(Participants) | Dose Escalation Cohort 1 | Dose Escalation Cohort 2 | Dose Expansion Cohort | Total |
|---|---|---|---|---|
| Female | 3 | 3 | 56 | 62 |
| Male | 0 | 0 | 0 | 0 |
| Race/Ethnicity, Customized(Participants) | Dose Escalation Cohort 1 | Dose Escalation Cohort 2 | Dose Expansion Cohort | Total |
|---|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 1 | 1 |
| Not Hispanic or Latino | 3 | 3 | 50 | 56 |
| Unknown | 0 | 0 | 5 | 5 |
PDFs hosted by the registry, ClinicalTrials.gov.
Ran from Nov 2018 to primary completion in Feb 2024, 63 months.
Results were first posted in Jun 2025, 1 year 4 months after primary completion.
Of 388 industry-sponsored phase 1 interventional studies under Breast Neoplasms, half reached primary completion within 39 months of starting (the median), counting those still running; a quarter within 22 and three quarters within 56. This study's 63 months is above that.
Counting every sponsor, half of 759 studies reached it within 44 months; a quarter within 25 and three quarters within 66.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Apr 2025. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: CH 5132799