A First-in-Human, Open-label, Phase 1/2 Clinical Trial to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of HMBD-501 in Patients With Advanced-Stage, Relapsed/Refractory HER3-Expressing Solid Tumors
This study is a Phase 1/2, first-in-human, open-label, clinical trial to assess the safety, tolerability, pharmacokinetics and preliminary efficacy of HMBD-501 in patients with advanced-stage, relapsed and/or refractory human epidermal growth factor receptor 3 (HER3)-expressing solid tumors. The study consists of 2 phases: a dose escalation phase (Phase 1) and a dose expansion phase (Phase 2). The primary objectives of Phase 1 are to characterize the overall safety and tolerability profile of increasing doses of HMBD-501 in patients with advanced-stage solid tumors and identify the recommended Phase 2 dose (RP2D) of ENV-501. During Phase 1, successive cohorts of patients will receive escalating doses of HMBD-501. The results of the dose escalation will determine the RP2D and dosing schedule of HMBD-501 to be administered in the Phase 2 part of the study. The primary objective of Phase 2 is to evaluate the preliminary clinical efficacy of HMBD-501 in dose expansion cohorts.
• Body weight ≥ 40 kg.
• Willing and able to provide signed written informed consent before any study-related screening procedures are performed.
• Patients with histologically or cytologically confirmed diagnosis of advanced-stage or metastatic HER3+ solid tumors that are relapsed or refractory to or ineligible for standard therapy, or for whom no standard therapy is available; or the patient has documented their refusal of standard of care therapies. These include the following:
‣ Unresectable or metastatic cutaneous melanoma (HER3+)
⁃ Locally advanced or metastatic mutated EGFR (mEGFR) NSCLC (HER3+)
⁃ Unresectable, locally advanced or metastatic breast cancer
⁃ Relapsed or refractory solid tumors, with documented HER3+ expression such as Pancreatic Ductal Adenocarcinoma (PDAC) and gastric cancers, may be allowed in the protocol following sponsor approval on a case-by -case basis.
• If molecular pathology report to confirm HER3+ status is not available, willingness to undergo fresh tumor biopsy for retrospective assessment of HER3+ status following enrollment..
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2.
• Contraceptive requirements:
‣ Women of childbearing potential (WOCBP) must use contraception from at least 28 days prior to study start, during the study, and for at least 6 months after the last dose of study drug.
⁃ Males who are sexually active with partner(s) who are WOCBP must agree to use a male condom with spermicide beginning at study start, during the study and for at least 6 months after the last dose of study drug.
• Females must:
‣ Agree to not donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for at least 6 months after the last dose of study drug.
⁃ Agree to not breastfeed and do not plan to become pregnant during the study and for at least 6 months after the last dose of study drug.
• Males must:
‣ Agree to not donate sperm beginning at study start, during the study, and for at least 6 months after the last dose of study drug.
⁃ Agree to not plan to father a child beginning at study start, during the study, and for at least 6 months after last dose of study drug.
• Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.