Study of Oraxol and Pembrolizumab in Subjects With Advanced Solid Tumors

• Status: Recruiting
• Trial end date: 2023-06-30
• Target enrollment: 0
• Participant gender: All

Summary

This is an open-label, Phase 1 dose-escalation study followed by a 3-arm expansion cohort of Oraxol administered in combination with pembrolizumab.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Athenex, Inc.
• Treatments: Albumin-Bound Paclitaxel; Paclitaxel; Pembrolizumab

Criteria

Inclusion Criteria:

• Able to understand and sign an informed consent form

• Age ≥18 years

• Dose Escalation: Histologically confirmed metastatic or unresectable solid tumors for which pembrolizumab is an FDA-approved therapy

• Dose Expansion: Histologically confirmed diagnosis of advanced or metastatic urothelial carcinoma, gastric/gastro-esophageal adenocarcinoma or NSCLC. NSCLC patients with EGFR or ALK translocation must have previously progressed on FDA-approved therapy for these aberrations (accounting for PD-1 expression in each histologic subtype)

• Dose Expansion: Must have stable disease or progressed on previously failed anti-PD1 or anti-PD-L1 therapy

• Previously progressed on or become intolerant of at least 1 line of systemic chemotherapy for metastatic or advanced disease

• Must have at least one measurable site of disease as defined as per RECIST v1.1 criteria

• ECOG Performance Status ≤1

• Must have adequate hematology, blood chemistry, liver function and renal function.

• Willing and able to comply with scheduled visits, treatment plan and laboratory tests

• No concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, breast, or bladder

• Subjects receiving warfarin who are otherwise eligible and who may be appropriately managed with low molecular weight heparin, in the opinion of the Investigator, may be enrolled in the study provided they are switched to low molecular weight heparin at least 7 days prior to receiving study treatment.

• Men who are sterile (including vasectomy confirmed by post vasectomy semen analysis) OR agree to use a condom with spermicide and to not donate sperm during the study and for at least 30 days following last dose of Oraxol

• Female subjects must be postmenopausal (>12 months without menses) or surgically sterile (ie, by hysterectomy and/or bilateral oophorectomy) or must be using effective contraception (ie, oral contraceptives, intrauterine device, double barrier method of condom and spermicide) and agree to continue use of contraception for 30 days after their last dose of assigned study treatment. Abstinence is also an acceptable form of contraception.

• Subjects who are of childbearing potential must have a negative serum pregnancy test at Screening and within 96 hours before Week 1 dosing.

• Willing to return for follow-up

• Willing to provide blood samples for correlative research purposes

• Life expectancy of at least 3 months

Exclusion Criteria:

• Subjects with history of prior treatment with taxanes (eg, paclitaxel, docetaxel, cabazitaxel) in expansion cohorts only

• History of prior significant toxicity from anti-PD-1 or anti-PDL1 therapy requiring discontinuation of treatment

• Subjects who have not recovered from recent anti-cancer therapy received.

• Current or prior use of immunosuppressive medication within 14 days before the first dose of pembrolizumab.

• Vaccinated with live, attenuated vaccines within 28 days of the first dose of the study drug

• Active or prior documented autoimmune or inflammatory disorders. The following are exceptions to this criterion:

• Subjects with vitiligo or alopecia

• Subjects with hypothyroidism (eg, following Hashimoto's thyroiditis) stable on hormone replacement therapy or psoriasis not requiring systemic treatment

• Subject has impairment of GI function or GI disease that may significantly alter the absorption of study drugs (including gastric bypass surgery and total gastrectomy). Subjects with partial gastrectomy may be included in the trial.

• Uncontrolled concurrent illness.

• Known or suspected diagnosis of human immunodeficiency virus (HIV) or chronic active Hepatitis B or C, or cirrhosis.

• Clinically significant pulmonary illness resulting in Grade ≥2 hypoxia.

• Symptomatic or uncontrolled brain metastases requiring current treatment (less than 28 days from last cranial radiation or 28 days from last steroids use).

• Impaired cardiac function or clinically significant cardiac disease.

• Subjects with a healing or open wound

• Lack of recovery of prior AEs to Grade ≤1 severity (NCI CTCAE v4.03) (except alopecia) due to medications administered prior to the first dose of the trial drugs.

• Any other condition or finding (including social situation) that in the opinion of the Investigator may render the patient at excessive risk for treatment complications or may not be able provide evaluable outcome information.

• Pregnant or breast-feeding women

• Known allergy to any of the formulation components of Oraxol (oral paclitaxel or HM30181A) or