Clinical Trial 23745

• Overview

  Study Title:

  A Phase 1, First-in-Human Study of MEN2312, A KAT6 Inhibitor, as Monotherapy and in Combination in Participants with Advanced Breast Cancer

  Summary:

  This is a first-in-human study of MEN2312, a lysine acetyltransferase 6 (KAT6) inhibitor, in adult participants with advanced breast cancer.

  Objective:

  Primary Objectives: * Parts A, C, E and G: To identify the MTD/MAD in Part A and recommended expansion doses (RDE) in Parts C, E and G for MEN2312 in advanced breast cancer * Parts D, F, and H: Establish the recommended phase 2 dose (RP2D) of MEN2312 when administered in combination Secondary Objectives: * Parts A, C, D, E, F, G and H: Evaluate the safety and tolerability of MEN2312 as monotherapy and in combination * Parts A, C, D, E, F, G and H: To evaluate preliminary antitumor activity of MEN2312 * Part A: Characterize the PK profile of MEN2312 in plasma and urine and evaluate the effect of food on the PK when administered as monotherapy * Parts C, D, E, F G and H: Describe the PK profile of MEN2312 and other drugs when administered in combination * Parts C, D, E, F G and H: Evaluate PK DDI between MEN2312 and other drugs in combination

• Treatments

  Therapies:

  KAT6 Inhibitor; Therapy (NOS)

  Medications:

  Capivasertib (); Elacestrant (); Faslodex (fulvestrant); MEN2312 (); everolimus (RAD001); fulvestrant ()

• Inclusion Criteria

  Key Inclusion Criteria:
  • Participant has advanced (locoregionally recurrent or metastatic) breast cancer not amenable to curative therapy.
  • Participants must have at least 1 measurable lesion as defined by RECIST version 1.1, that has not been previously irradiated and / or at least 1 lytic or mixed (lytic +sclerotic) bone lesion with identifiable soft tissue components meeting the definition of measurability by RECIST version 1.1 that can be evaluated by CT or MRI; participants with sclerotic / osteoblastic bone lesions only in the absence of measurable disease are not eligible.
  • Participant must have received at least one prior line of endocrine therapy for advanced/metastatic disease OR participant who has radiological evidence of breast cancer recurrence or progression during or within 12 months from the end of adjuvant treatment with ET, as these participants are considered as first-line relapsed participants.
  • Progression on previous CDK4/6 inhibitor treatment in combination with fulvestrant or AI is required.
  • ECOG performance status of 0 or 1
  • Adequate bone marrow and organ function as defined in protocol.
  • Presence of genetic alterations in PIK3CA/AKT1/PTEN in participants' tumor tissue.
  • Female participants of childbearing potential must have a negative serum pregnancy test at screening and within 5 days (120 hours) prior to first dose, abstain from breastfeeding, agree to use highly effective methods of contraception per APPENDIX B: CONTRACEPTION GUIDANCE AND CHILDBEARING POTENTIALAPPENDIX or abstain from heterosexual intercourse throughout the entire study period, within 28 days of the first dose of study treatment and for 276 days after trial therapy discontinuation;
  • Men and women must agree to abstain from donating sperm or ova and agree to use a highly effective method of contraception as per Appendix B, during the treatment period and for 186 and 276 days after the last dose of study treatment, respectively. Note: For participants enrolled in the combination part of the trial, the duration for abstaining from donating sperms or ova and for using a highly effective method of contraception will be according to the prescribing information and core data sheet of the combination drugs as per Appendix B
  • Additional criteria will apply

• Exclusion Criteria

  Key Exclusion Criteria:
  • Active or newly diagnosed central nervous system metastases.
  • Participants with advanced, symptomatic visceral spread, who are at risk of life-threatening complications in the short term, including massive uncontrolled effusions (peritoneal, pleural, pericardial), pulmonary lymphangitis, or liver involvement >50%.
  • Patricipants with any toxicities related to prior radiation therapy that have not resolved to baseline or to NCI CTAE v5 Grade > Additional criteria will apply

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