AN0025 and Pembrolizumab Combination in Advanced Solid Tumors

Inclusion Criteria

• •1. Age ≥18 years at the time of informed consent.
• •2. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• •3. Life expectancy ≥3 months.
• •4. Diagnosed with histologically confirmed locally advanced and nonresectable, or metastatic disease.
• •Patients diagnosed with one of the following tumor types:
• •A. Urothelial carcinoma of the bladder B. NSCLC, Squamous or Non-Squamous C. TNBC D. Cervical cancer E. MSS CRC
• •5. Have progressed on treatment with an anti-PD-1/PD-L1monoclonal antibody (mAb) administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies (cohort A, B or C) and have failed available standard of care treatment or deemed inappropriate candidates for additional standard treatments by the investigator. PD-1 treatment progression is defined by meeting all of the following criteria:
• •For cohort A, B and C:
• •1. Has received at least 2 doses of an approved anti-PD-1/PD-L1 mAb.
• •2. Has demonstrated disease progression after PD-1/PD-L1 as defined by RECIST v1.1. The initial evidence of disease progression (PD) is to be confirmed by a second assessment no less than four weeks from the date of the first documented PD, in the absence of rapid clinical progression. i,ii
• •3. Progressive disease has been documented within 12 weeks from the last dose of anti-PD-1/L1 mAb.
• •i. Seymour et al; iRECIST: Guidelines for response criteria for use in trials testing immunotherapeutics. Lancet Oncol 18: e143-52 ii. This determination is made by the investigator. Once PD is confirmed, the initial date of PD documentation will be considered the date of disease progression.
• •For cohort B (NSCLC):
• •1. Prior treatments must include an anti-PD-1/PD-L1 mAb AND a platinum-based chemotherapy.
• •2. Must include anti-PD-1/PD-L1 mAb or platinum-based chemotherapy was used in one of the following settings:
• •* Locally advanced and unresectable
• •* Metastatic disease
• •* Adjuvant setting with disease progression occurred within 6 months after the last dose
• •3. Must include anti-PD-1/PD-L1 mAb or platinum-based chemotherapy was used in one of the following settings:
• •* Locally advanced and unresectable
• •* Metastatic disease
• •* Adjuvant setting with disease progression occurred within 6 months after the last dose or with no prior anti-PD-1/PD-L1 therapy and failed standard of care treatment (cohorts C, D, or E).
• •6. For cohorts A, C, D and E: Have received no more than 3 prior lines of systemic therapy for advanced disease. Prior therapy in an adjuvant or neoadjuvant setting is not considered as a prior line of systemic therapy. For cohort B (NSCLC), there is no limitation to the number of prior lines of systemic therapy.
• •7. Have measurable disease per RECIST 1.1 as assessed by the local site investigator and/or radiologist. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• •8. Have provided signed informed consent for the trial
• •9. Have provided archival tumor tissue sample obtained after anti-PD-1/PD-L1 or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Formalin fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.
• •10. Left ventricular ejection fraction (LVEF) greater than 50% on echocardiography or multiple gated acquisition (MUGA) scan.
• •11. Have adequate organ function.
• •12. Willing and able to comply with all aspects of the protocol
• •13. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
• •1. Not a woman of childbearing potential Women are considered post-menopausal and not of child-bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) at least six weeks prior to Screening. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment is she considered not of child-bearing potential.
• •2. Woman of childbearing potential who agrees to follow contraceptive guidance during the treatment period and for at least 120 days after the last dose of study treatment.
• •Highly effective contraception is defined as either:
• •* Total abstinence: When this is in line with the preferred and usual lifestyle of the patient. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception.)
• •* Female sterilization: When the female study patient has had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment.
• •* Male partner sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate). For female study patients, the vasectomized male partner should be the sole partner for that patient.
• •* Using a combination of any two of the following:
• •* Placement of an intrauterine device (IUD) or intrauterine system (IUS), and
• •* Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository.
• •* Hormonal contraception methods (e.g., oral, injected, implanted).
• •14. A male participant must agree to use contraception during the treatment period and for at least 120 days after the last dose of study treatment.