Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication VEPPANU is indicated for the treatment of adults with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, estrogen receptor-1 (ESR1) -mutated advanced or metastatic breast cancer, as detected by an FDA-authorized test, with disease progression following at least one line of endocrine therapy. FDA label
Vepdegestrant · 1 trial · 1 indication
DLT was defined as any adverse event (AE) or abnormal laboratory value which were related to vepdegestrant and assessed as unrelated to mBC, intercurrent illness, or concomitant medications occurring during the first 28 days of treatment that met at least 1 of the study specified criteria.
An AE is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Treatment-related AE was any untoward medical occurrence attributed to study treatment in a participant who received study treatment. Relatedness was judged by investigator. Serious AE (SAE) was an AE resulted in any of the following outcomes: death, inpatient hospitalization or prolongation of existing hospitalization; was life-threatening experience (immediate risk of dying); resulted in persistent or significant disability/incapacity; congenital anomaly/birth defect or was otherwise considered medically important. A TEAE was an AE occurring on/after the date of first dose of study medication and within 30 days of the last dose of study medication. TEAEs included both Serious TEAEs and non-serious TEAEs.
CBR: percentage of participants with summation of complete response (CR), partial response (PR) or stable disease (SD) of 24 weeks duration or longer. CR: disappearance of all target lesions (TLs) and non-TLs and normalization of tumor marker levels initially above upper limits of normal. PR: \>30% decrease in the sum of the longest diameter (LD) of TLs, taking as reference the baseline sum LD. SD of TLs was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum LD since the treatment started. SD of non-TLs Persistence of one or more non-TLs or/and maintenance of tumor marker level above the normal limits. PD: \>20% increase in the sum of the LD of TLs, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions and/or unequivocal progression of existing non-TLs.
DLT was defined as any AE or abnormal laboratory value which were related to vepdegestrant and assessed as unrelated to mBC, intercurrent illness, or concomitant medications occurring during the first 28 days of treatment that met at least 1 of the study specified criteria.
An AE is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Treatment-related AE was any untoward medical occurrence attributed to study treatment in a participant who received study treatment. Relatedness was judged by investigator. SAE was an AE resulted in any of the following outcomes: death, inpatient hospitalization or prolongation of existing hospitalization; was life-threatening experience (immediate risk of dying); resulted in persistent or significant disability/incapacity; congenital anomaly/birth defect or was otherwise considered medically important. A TEAE was an AE occurring on/after the date of first dose of study medication and within 30 days of the last dose of study medication. TEAEs included both Serious TEAEs and non-serious TEAEs.
MTD is the highest dose of a drug that can be given to participants without causing unacceptable DLTs, as determined during a clinical study.
| Arm | Type | Description |
|---|---|---|
| Part A - Phase 1: Vepdegestrant 30 mg (Dose Escalation) | EXPERIMENTAL | Participants received vepdegestrant 30 milligrams (mg) orally once daily (QD) with food in continuous daily dosing (on 28-day cycles). Vepdegestrant was administered in tablet form. Treatment was continued at the investigator's discretion until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Participants were followed for survival every 3 months after the end of treatment (EOT) or Follow-up visit (whichever occurred later) until death, lost to follow-up, or withdrawal of consent. |
| Part A - Phase 1: Vepdegestrant 60 mg (Dose Escalation) | EXPERIMENTAL | Participants received vepdegestrant 60 mg orally QD with food in continuous daily dosing (on 28-day cycles). Vepdegestrant was administered in tablet form. Treatment was continued at the investigator's discretion until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Participants were followed for survival every 3 months after EOT or Follow-up visit (whichever occurred later) until death, lost to follow-up, or withdrawal of consent. |
| Part A - Phase 1: Vepdegestrant 100 mg (Dose Escalation) | EXPERIMENTAL | Participants received vepdegestrant 100 mg orally QD with food in continuous daily dosing (on 28-day cycles). Vepdegestrant was administered in tablet form. Treatment was continued at the investigator's discretion until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Participants were followed for survival every 3 months after EOT or Follow-up visit (whichever occurred later) until death, lost to follow-up, or withdrawal of consent. |
| Part A - Phase 1: Vepdegestrant 120 mg (Dose Escalation) | EXPERIMENTAL | Participants received vepdegestrant 120 mg orally QD with food in continuous daily dosing (on 28-day cycles). Vepdegestrant was administered in tablet form. Treatment was continued at the investigator's discretion until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Participants were followed for survival every 3 months after EOT or Follow-up visit (whichever occurred later) until death, lost to follow-up, or withdrawal of consent. |
| Part A - Phase 1: Vepdegestrant 180 mg (Dose Escalation) | EXPERIMENTAL | Participants received vepdegestrant 180 mg orally QD with food in continuous daily dosing (on 28-day cycles). Vepdegestrant was administered in tablet form. Treatment was continued at the investigator's discretion until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Participants were followed for survival every 3 months after EOT or Follow-up visit (whichever occurred later) until death, lost to follow-up, or withdrawal of consent. |
| Part A - Phase 1: Vepdegestrant 200 mg (Dose Escalation) | EXPERIMENTAL | Participants received vepdegestrant 200 mg orally QD with food in continuous daily dosing (on 28-day cycles). Vepdegestrant was administered in tablet form. Treatment was continued at the investigator's discretion until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Participants were followed for survival every 3 months after EOT or Follow-up visit (whichever occurred later) until death, lost to follow-up, or withdrawal of consent. |
| Part A - Phase 1: Vepdegestrant 360 mg (Dose Escalation) | EXPERIMENTAL | Participants received vepdegestrant 360 mg orally QD with food in continuous daily dosing (on 28-day cycles). Vepdegestrant was administered in tablet form. Treatment was continued at the investigator's discretion until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Participants were followed for survival every 3 months after EOT or Follow-up visit (whichever occurred later) until death, lost to follow-up, or withdrawal of consent. |
| Part A - Phase 1: Vepdegestrant 500 mg (Dose Escalation) | EXPERIMENTAL | Participants received vepdegestrant 500 mg QD or 250 mg twice daily (BID), orally with food in continuous daily dosing (on 28-day cycles). Vepdegestrant was administered in tablet form. Treatment was continued at the investigator's discretion until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Participants were followed for survival every 3 months after EOT or Follow-up visit (whichever occurred later) until death, lost to follow-up, or withdrawal of consent. |
| Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation) | EXPERIMENTAL | Participants received vepdegestrant 700 mg QD or as BID dose (400 mg in the morning and 300 mg in the evening), orally with food in continuous daily dosing (on 28-day cycles). Vepdegestrant was administered in tablet form. Treatment was continued at the investigator's discretion until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Participants were followed for survival every 3 months after EOT or Follow-up visit (whichever occurred later) until death, lost to follow-up, or withdrawal of consent. |
| Part B - Phase 2: Vepdegestrant 200 mg (Dose Expansion) | EXPERIMENTAL | Participants received vepdegestrant 200 mg orally QD with food in continuous daily dosing (on 28-day cycles). Vepdegestrant was administered in tablet form. Treatment was continued at the investigator's discretion until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Participants were followed for survival every 3 months after EOT or Follow-up visit (whichever occurred later) until death, lost to follow-up, or withdrawal of consent. |
| Part B - Phase 2: Vepdegestrant 500 mg (Dose Expansion) | EXPERIMENTAL | Participants received vepdegestrant 500 mg orally QD with food in continuous daily dosing (on 28-day cycles). Vepdegestrant was administered in tablet form. Treatment was continued at the investigator's discretion until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Participants were followed for survival every 3 months after EOT or Follow-up visit (whichever occurred later) until death, lost to follow-up, or withdrawal of consent. |
| Part C - Phase 1b: Vepdegestrant 180 mg+ Palbociclib 125 mg (Dose Escalation) | EXPERIMENTAL | Participants initially received vepdegestrant 180 mg tablets orally QD with food then upon availability of the 100-mg tablets was rounded up to 200 mg QD, given continuously (28-day cycle) in combination with palbociclib 125 mg orally QD for 21 days followed by 7 days off treatment to complete a 28-day cycle. Vepdegestrant was administered in tablet form and palbociclib in capsule form. Treatment was continued at the investigator's discretion until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Participants were followed up for survival after at least 3 months after the EOT or Follow-up visit (whichever occurred later). |
| Part C - Phase 1b: Vepdegestrant 200 mg + Palbociclib 125 mg (Dose Expansion) | EXPERIMENTAL | Participants received vepdegestrant 200 mg orally QD with food, given continuously (28-day cycle) in combination with palbociclib 125 mg orally QD for 21 days followed by 7 days off treatment to complete a 28-day cycle. Vepdegestrant was administered in tablet form and palbociclib in capsule form. Treatment was continued at the investigator's discretion until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Participants were followed for survival every 3 months after EOT or Follow-up visit (whichever occurred later) until death, lost to follow-up, or withdrawal of consent. |
| Part C - Phase 1b: Vepdegestrant 400 mg + Palbociclib 125 mg (Dose Escalation) | EXPERIMENTAL | Participants received vepdegestrant 400 mg orally QD with food, given continuously (28-day cycle) in combination with palbociclib 125 mg orally QD for 21 days followed by 7 days off treatment to complete a 28-day cycle. Vepdegestrant was administered in tablet form and palbociclib in capsule form. Treatment was continued at the investigator's discretion until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Participants were followed for survival every 3 months after EOT or Follow-up visit (whichever occurred later) until death, lost to follow-up, or withdrawal of consent. |
| Part C - Phase 1b: Vepdegestrant 500 mg + Palbociclib 125 mg (Dose Expansion) | EXPERIMENTAL | Participants received vepdegestrant 500 mg orally QD with food, given continuously (28-day cycle) in combination with palbociclib 125 mg orally QD for 21 days followed by 7 days off treatment to complete a 28-day cycle. Vepdegestrant was administered in tablet form and palbociclib in capsule form. Treatment was continued at the investigator's discretion until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Participants were followed for survival every 3 months after EOT or Follow-up visit (whichever occurred later) until death, lost to follow-up, or withdrawal of consent. |
| Part C - Phase 1b: Vepdegestrant 200 mg + Palbociclib 100 mg (Dose Expansion) | EXPERIMENTAL | Participants initially received palbociclib 100 mg orally QD starting on C1D1, for 21 days followed by 7 days off and then received vepdegestrant 200 mg QD with food on C1D9, given continuously (28-day cycle). Palbociclib was administered alone from C1D1 to C1D8 prior to starting vepdegestrant on C1D9. Vepdegestrant was administered in tablet form and palbociclib in capsule form. Treatment was continued at the investigator's discretion until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Participants were followed for survival every 3 months after EOT or follow-up visit (whichever occurred later) until death, lost to follow-up, or withdrawal of consent. |
| Name | Type | Description |
|---|---|---|
| Vepdegestrant | DRUG | Vepdegestrant administered QD for 28-day cycles |
| Palbociclib | DRUG | Daily oral dosages of vepdegestrant for 28 days in combination with palbociclib for 21 days |
Inclusion Criteria: Part A, Part B, and Part C: * Participants at least 18 years of age at the time of signing the informed consent. * Participants must have histologically or cytologically confirmed ER+ and HER2- advanced breast cancer for which standard curative therapy is no longer effective or...
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Vepdegestrant is being developed for the treatment of ER+/HER2- locally advanced or metastatic breast cancer. It is an investigational small molecule that has been studied both as a single agent and in combination with palbociclib (IBRANCE). It has received a Fast Track designation from the FDA.
Vepdegestrant targets the estrogen receptor, functioning as a selective estrogen receptor degrader (SERD). It belongs to the -estrant class of small molecules designed to bind and degrade the estrogen receptor, which is a key driver in ER+ breast cancer.
Vepdegestrant is being developed by Arvinas, Inc., a biopharmaceutical company traded on the Nasdaq under the ticker symbol ARVN. Arvinas is focused on targeted protein degradation and is the sponsor of the clinical program for this asset.
Vepdegestrant is in Phase 1 clinical development. It is an investigational drug and has not been approved by the FDA for any indication. The Phase 1/2 trial evaluating it in breast cancer has been completed.
Vepdegestrant has been evaluated in a Phase 1/2 trial, NCT04072952, titled "A Phase 1/2 Trial of ARV-471 Alone and in Combination With Palbociclib (IBRANCE®) in Participants With ER+/HER2- Locally Advanced or Metastatic Breast Cancer." The trial enrolled 219 participants and is completed.