Study of Oraxol and Pembrolizumab in Subjects With Advanced Solid Tumors

NCT03588039 | Terminated Phase 1 FDA Drug

• 2 other identifiers: KX-ORAX-011KEYNOTE-E06
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 4

Brief Summary

This is an open-label, Phase 1 dose-escalation study followed by a 2-arm expansion cohort of Oraxol administered in combination with pembrolizumab.

Conditions

Solid Tumor

Outcome Measures

Primary Outcomes (2)

• Determination of MTD

  dose limiting toxicities occuring in the first cycle of therapy

  3 weeks

• Tumor response rate

  Proportion of subjects in each arm and part 2 with confirmed tumor response

  24 months

Secondary Outcomes (7)

• Progression free survival (PFS)

  24 months

• Overall survival (OS)

  24 months

• Duration of response (DOR)

  24 months

• Pharmacokinetics of Oraxol

  Day 1 and day 2

• Disease Control Rate (DCR)

  24 months

Study Arms (8)

Dose escalation-Arm 1

EXPERIMENTAL

During the dose escalation period Oraxol will be administered once daily for 2 days per week for 2 weeks followed by 1 week off treatment (2 weeks on and 1 week off). Pembrolizumab will be administered on Day 1 of each 3-week cycle.

Drug: Oraxol; Biological: Pembrolizumab

Dose escalation-Arm 2

EXPERIMENTAL

During the dose escalation period Oraxol will be administered once daily for 3 days per week for 2 weeks followed by 1 week off treatment (2 weeks on and 1 week off). Pembrolizumab will be administered on Day 1 of each 3-week cycle.

Drug: Oraxol; Biological: Pembrolizumab

Dose escalation-Arm 3

EXPERIMENTAL

During the dose escalation period Oraxol will be administered once daily for 4 days per week for 2 weeks followed by 1 week off treatment (2 weeks on and 1 week off). Pembrolizumab will be administered on Day 1 of each 3-week cycle.

Drug: Oraxol; Biological: Pembrolizumab

Dose escalation-Arm 4

EXPERIMENTAL

During the dose escalation period Oraxol will be administered once daily for 5 days per week for 2 weeks followed by 1 week off treatment (2 weeks on and 1 week off). Pembrolizumab will be administered on Day 1 of each 3-week cycle.

Drug: Oraxol; Biological: Pembrolizumab

Dose escalation-Arm 5

EXPERIMENTAL

During the dose escalation period Oraxol will be administered once daily for 5 days per week for 2 weeks followed by 1 week off treatment (2 weeks on and 1 week off). Pembrolizumab will be administered on Day 1 of each 3-week cycle.

Drug: Oraxol; Biological: Pembrolizumab

Dose escalation-Arm 6

EXPERIMENTAL

During the dose escalation period Oraxol will be administered once daily for 5 days per week for 2 weeks followed by 1 week off treatment (2 weeks on and 1 week off). Pembrolizumab will be administered on Day 1 of each 3-week cycle.

Drug: Oraxol; Biological: Pembrolizumab

Dose expansion-Gastric/GE

EXPERIMENTAL

The dose expansion period will enroll subjects with gastric/gastro-esophageal cancer to further evaluate the activity and safety of the study treatment. Oraxol will be administered at the dose determined from part 1 for 2 out of 3 weeks. Pembrolizumab will be administered on Day 1 of each 3-week cycle.

Drug: Oraxol; Biological: Pembrolizumab

Dose expansion-NSCLC cancer

EXPERIMENTAL

The dose expansion period will enroll subjects with NSCLC to further evaluate the activity and safety of the study treatment. Oraxol will be administered at the dose determined from part 1 for 2 out of 3 weeks. Pembrolizumab will be administered on Day 1 of each 3-week cycle.

Drug: Oraxol; Biological: Pembrolizumab

Interventions

Oraxol DRUG

Oral paclitaxel will be supplied in capsules and oral HM30181AK-US will be supplied in tablets

Also known as: oral HM30181A + oral paclitaxel

Dose escalation-Arm 1; Dose escalation-Arm 2; Dose escalation-Arm 3; Dose escalation-Arm 4; Dose escalation-Arm 5; Dose escalation-Arm 6; Dose expansion-Gastric/GE; Dose expansion-NSCLC cancer

Pembrolizumab BIOLOGICAL

Intravenously administered

Also known as: Keytruda

Dose escalation-Arm 1; Dose escalation-Arm 2; Dose escalation-Arm 3; Dose escalation-Arm 4; Dose escalation-Arm 5; Dose escalation-Arm 6; Dose expansion-Gastric/GE; Dose expansion-NSCLC cancer

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eligible subjects must have/be:
• 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 FDAapproved therapy
• Dose Expansion: Histologically confirmed diagnosis of advanced or metastatic NSCLC or gastric/gastro-esophageal adenocarcinoma:
• NSCLC:
• Subjects with actionable mutations or alterations must have progressed on prior FDA approved therapy for these aberrations.
• Subjects must have progressed on a prior FDA-approved single agent immunotherapy (antiPD1/anti-PD-L1) in first line (1L) or progressed on a prior FDA approved immunotherapy + chemotherapy combination therapy in 1L, as long as the chemotherapy did not include a taxane.
• Gastric/Gastro-esophageal
• Histologically confirmed diagnosis of advanced or metastatic gastric/gastro-esophageal adenocarcinoma or esophageal squamous cell carcinoma.
• Subjects must have progressed on previous anti-PD-1 therapy as single agent or combination therapy.
• Must have at least one measurable site of disease as defined as per RECIST v1.1 criteria
• ECOG Performance Status ≤1
• The following laboratory values obtained ≤14 days prior to Cycle 1/Day 1 dosing:
• Absolute neutrophil count (ANC) ≥1.5 x 109/L

You may not qualify if:

• Eligible subjects must not have/be:
• 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-PD-L1 therapy requiring discontinuation of treatment
• Subjects who have received recent anti-cancer therapy defined by:
• Chemotherapy, immunotherapy, hormonal therapy and monoclonal antibodies (but excluding nitrosurea, mitomycin-C, targeted therapy, and radiation) ≤28 days prior to starting study drug, or who have not recovered from side effects of such therapy
• Last administration of nitrosurea or mitomycin-C ≤42 days prior to starting study drug, or who have not recovered from the side effects of such therapy
• Targeted therapy (eg, sunitinib, sorafenib, pazopanib) ≤14 days prior to starting study drug, or who have not recovered from the side effects of such therapy; or
• Radiotherapy ≤28 days prior to starting study drug, or ≤14 days prior to starting study drug in the case of localized radiotherapy (eg, for analgesic purpose or for lytic lesions at risk of fracture), or who have not recovered from radiotherapy toxicities.
• Current or prior use of immunosuppressive medication within 14 days before the first dose of pembrolizumab. The following are exceptions to this criterion: Intranasal, inhaled, topical corticosteroids, or local corticosteroid, injections (eg, intra-articular injection), systemic corticosteroids at doses not to exceed 10 mg/day of prednisone or its equivalent.
• Vaccinated with live, attenuated vaccines within 28 days of the first dose of the study drug
• Active or prior documented autoimmune or inflammatory disorders (including but not limited to inflammatory bowel disease \[eg, colitis, Crohn's disease\], celiac disease, or other serious gastrointestinal (GI) chronic conditions associated with diarrhea; type 1 diabetes mellitus; multiple sclerosis; systemic lupus erythematosus; Wegener's granulomatosis; myasthenia gravis; Graves' disease; rheumatoid arthritis; hypophysitis; uveitis; etc) within the past 3 years prior to the start of treatment. 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.
• Subjects who have undergone major surgery (eg, intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic injury ≤28 days prior to starting study treatment, or subjects who have had minor procedures, percutaneous biopsies or placement of vascular access device ≤7 days prior to starting study drug, or who have not recovered from side effects of such procedure or injury

Sponsors & Collaborators

• Athenex, Inc.: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (4)

Mayo Clinic

Phoenix, Arizona, 85054, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Interventions

Paclitaxel; pembrolizumab

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• David Cutler, MD

  Sr. Vice President of Clinical Development

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 13, 2018
• First Posted: July 17, 2018
• Study Start: October 25, 2018
• Primary Completion: May 12, 2023
• Study Completion: May 12, 2023
• Last Updated: May 19, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)