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Phase 1/2 Study of ETX-636 in Participants With Advanced Solid Tumors

ConditionsAdvanced Solid TumorsAdvanced Breast Cancer
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorEnsem Therapeutics

About this trial

Phase 1/2, open-label study of ETX-636 in participants with advanced solid tumors

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Metastatic or locally advanced and unresectable solid tumor that has progressed on or after at least one available therapy.

Tumor harboring an activating PIK3CA mutation detected in either tumor tissue or ctDNA.

At least 1 measurable lesion or evaluable disease per RECIST v1.1.

An ECOG performance status score of 0 or 1.

Disqualifiers

Has history (within ≤2 years before screening) of a solid tumor or hematological malignancy that is histologically distinct from the cancers being studied.

Has symptomatic brain or spinal metastases or a known or suspected history of untreated or uncontrolled central nervous system (CNS) involvement.

Has an established diagnosis of diabetes mellitus type 1 or has uncontrolled diabetes mellitus type 2.

Has received treatment with any local or systemic anticancer therapy or investigational anticancer agent within 14 days prior to start of treatment.

Trial design

Design model

Sequential

Treatments tested in this trial

  • ETX-636 dose escalation

    Drug

    ETX-636 is a pan-mutant-selective PI3Kα Inhibitor and degrader in the form of an oral tablet that will be taken once per day in 28-day cycles, to evaluate escalating dose levels.

  • ETX-636 dose escalation in combination with fulvestrant

    Drug

    ETX-636 is a pan-mutant-selective PI3Kα Inhibitor and degrader in the form of an oral tablet. ETX-636 will be taken in combination with fulvestrant in 28-day cycles, to evaluate escalating dose levels. EXT-636 is an oral tablet that will be taken once per day. Fulvestrant will be administered as an injection 2 weeks apart in the first 28 days, followed by monthly injections.

  • ETX-636 dose expansion in combination with fulvestrant

    Drug

    ETX-636 is a pan-mutant-selective PI3Kα Inhibitor and degrader in the form of an oral tablet. ETX-636 will be taken in combination with fulvestrant in 28-day cycles, to expand selected dose levels. EXT-636 is an oral tablet that will be taken once per day. Fulvestrant will be administered as an injection 2 weeks apart in the first 28 days, followed by monthly injections.

Treatment groups

233 Participants
are divided into 3 treatment groups
Group A: Part A Dose Escalation Monotherapy (Advanced Solid Tumors with PIK3CA mutation)Experimental treatment 1 intervention
Group B: Part B Dose Escalation Combination Therapy (HR+/HER2- locally advanced or metastatic breast cancer)Experimental treatment 1 intervention
Group C: Part C Dose Expansion Combination Therapy (HR+/HER2- locally advanced or metastatic breast cancer)Experimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

Evaluate Safety and Tolerability of ETX-636 monotherapy in Part A and ETX-636 plus fulvestrant combination therapy in Part B

Proportion of participants who experience at least 1 Dose Limiting Toxicity (DLT)

Time frame
First 28 days of treatment
2

Evaluate Safety and Tolerability of ETX-636 monotherapy in Part A and ETX-636 plus fulvestrant combination therapy in Part B

Incidence of AEs, treatment discontinuations due to AEs, changes from baseline in laboratory assessments, ECGs and vital signs.

Time frame
Average of 6 months
3

Select the Recommended Phase 2 Dose(s) (RP2D) in Part B to be further explored in Part C (combination therapy expansion)

Safety Parameters as described for primary outcomes

Time frame
Average of 6 months
4

Evaluate efficacy of ETX-636 plus fulvestrant combination therapy at the RP2D(s) in Part C

ORR and CBR according to RECIST v1.1

Time frame
Average of 6 months

Secondary outcomes

1

Characterize the Cmax (PK) of ETX-636 monotherapy in Part A and ETX-636 plus fulvestrant combination therapy in Part B

Maximum observed plasma concentration (Cmax) of ETX-636

Time frame
First 2 treatment cycles (each cycle is 28 days)
2

Characterize the Tmax (PK) of ETX-636 monotherapy in Part A and ETX-636 plus fulvestrant combination therapy in Part B

Calculated time to reach maximum observed plasma concentration of ETX-636

Time frame
First 2 treatment cycles (each cycle is 28 days)
3

Characterize the AUC (PK) of ETX-636 monotherapy in Part A and ETX-636 plus fulvestrant combination therapy in Part B

Calculated area under the plasma concentration curve (AUC) of ETX-636

Time frame
First 2 treatment cycles (each cycle is 28 days)
4

Measure PD effects of ETX-636 monotherapy in Part A and ETX-636 plus fulvestrant combination therapy in Part B and ETX-636 plus fulvestrant at the RP2D(s) in Part C

Change from baseline in ctDNA levels; Change from baseline in PD markers in paired biopsies

Time frame
First 3 cycles (each cycle is 28 days)

Other outcomes

Sponsors and contacts

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Ensem Therapeutics

Lead sponsor

Source ClinicalTrials.gov
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