a phase 1/2 clinical trial to assess the safety, tolerability, pharmacokinetics and preliminary efficacy of env-501 in patients with her3-expressing solid tumors

Conditions: Melanoma (Skin); Non Small Cell Lung Cancer; Breast Cancer

Summary: this study is a phase 1/2, first-in-human, open-label, clinical trial to assess the safety, tolerability, pharmacokinetics and preliminary efficacy of env-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 env-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 env-501. the results of the dose escalation will determine the rp2d and dosing schedule of env-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 env-501 in dose expansion cohorts.


Eligibility criteria:
inclusion criteria: * 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: 1. unresectable or metastatic cutaneous melanoma (her3+) 2. locally advanced or metastatic mutated egfr (megfr) nsclc (her3+) 3. unresectable, locally advanced or metastatic hormone receptor (hr)+/human epidermal growth factor receptor 2 (her2)- breast cancer (her3+) * if molecular pathology report to confirm her3+ status is not available, willingness to undergo fresh tumor biopsy for assessment of her3+ status. * eastern cooperative oncology group (ecog) performance status (ps) 0-2. * contraceptive requirements: 1. 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. 2. 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: 1. 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. 2. 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: 1. 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. 2. 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. exclusion criteria: * any of the following treatment interventions within the specified time frame prior to study drug administration at study start: 1. any anti-tumor-directed drug therapy within 21 days or 5 times the elimination half-life (whichever is shorter). 2. treatment with investigational drugs within 21 days. 3. major surgery within 21 days. 4. radiation therapy ≤4 weeks or radiotherapy that included \>30% of the bone marrow. 5. autologous or allogeneic stem cell transplantation or allogeneic tissue/organ transplant within 3 months. 6. cyp3a4 strong inhibitor (including any prescription or non-prescription drugs or herbal supplements) ≤4 half-lives. 7. cyp3a4 strong inducer ≤4 half-lives. 8. oatp1b inhibitor (including any prescription or non-prescription drugs or herbal supplements) ≤4 half-lives. * prior treatment with a her3-targeted adc or any exatecan- or exatecan-derivative-conjugated adc inhibitor as last line of therapy. * prior treatment with a topoisomerase i inhibitor as last line of therapy. * primary immune deficiency (e.g. congenital syndromes). * active and uncontrolled infections requiring intravenous antibiotic or antiviral treatment within 2 weeks prior to study start. * known/suspected hypersensitivity against env-501, human or humanized immunoglobulin gs (iggs), or their ingredients. * history of noninfectious or drug-induced pneumonitis or interstitial lung disease (ild). * known seropositivity (except after vaccination or confirmed cure for hepatitis) for human immunodeficiency virus (hiv), hepatitis b virus (hbv), or hepatitis c virus (hcv). * leptomeningeal disease, symptomatic or uncontrolled (active) brain metastasis (note: brain metastases not requiring steroids or anti-epileptic therapy are allowed if stable for ≥4 weeks prior to study start and patient is neurologically stable). * pregnant or wocbp who have a positive b-human chorionic gonadotropin (hcg) test result at screening or within 7 days prior to study start. * patients with second malignancies that are active (uncontrolled, metastatic) or requiring therapy. * patient who is an immediate family member (spouse, parent, child, or sibling; biological or legally adopted) of personnel directly affiliated with the study site or the sponsor.