Clinical trial NCT04880863: NAP in Combination With Docetaxel Following Obinutuzumab Pretreatment in Subjects With Checkpoint Inhibitor Pretreated Advanced or Metastatic NSCLC
Official title: Phase 2a Open-Label, Multicenter Trial of Naptumomab Estafenatox (NAP) in Combination With Docetaxel Following Obinutuzumab Pretreatment in Subjects With Checkpoint Inhibitor Pretreated Advanced or Metastatic Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer
Keywords: Advanced
Metastatic
Non small cell lung cancer
EGFR
ALK
Docetaxel
Naptumomab estafenatox
Obinutuzumab
NAP
Lead sponsor: NeoTX Therapeutics Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Translational Drug Development
First posted: 2021-05-11
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Subjects receive obinutuzumab, 1,000 mg, administered by IV infusion on Days -13 and -12 of the first treatment cycle in order to reduce the titer of anti-drug antibodies to NAP. NAP is administered by IV bolus on Days 1 - 4 of treatment cycles 1-6, followed by docetaxel on Day 5. Treatment cycles with the combination NAP/docetaxel are of 21 days in duration. Starting cycle 7, NAP at a higher dose is administered on Day 1 and docetaxel on Day 2, in 21 days treatment cycles. Once NAP is given as monotherapy and not earlier than C7, cycles are of 28 days of duration.
Primary purpose: TREATMENT

Brief summary: Phase 2a Open-Label, Multicenter Trial of Naptumomab Estafenatox (NAP), following Obinutuzumab Pretreatment, on Days -13 and -12. NAP will be administered on Days 1-4 of treatment cycles 1-6, followed by docetaxel on Day 5. Starting cycle 7, NAP at a higher dose will be administered on Day 1 only and docetaxel on Day 2, in 21 days treatment cycles. When NAP is administered as monotherapy and not earlier than cycle 7, NAP will be administered on Day 1 only and cycles will be of 28 days treatment cycle.

Detailed description: Patients must have received at least 1 and no more than 2 prior systemic regimens for the treatment of advanced/metastatic NSCLC. Patients were required to have progressed following treatment with both platinum-based chemotherapy and an anti-PD-(L)1 antibody administered either sequentially or concurrently. Entry into this trial was restricted to patients with incurable disease, including those whose disease had relapsed within 6 months after chemoradiotherapy for Stage III disease. Patients were to have available archival or fresh tissue collected for the retrospective determination of tumoral 5T4 levels.

Eligibility criteria: Main Inclusion Criteria:

1. Subjects must be at least 18 years of age
2. Subjects must have histologically and/or cytologically confirmed NSCLC
3. Subjects must have incurable (advanced or metastatic) disease at the time of enrolment
4. Subjects must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
5. Subjects must provide signed informed consent prior to any study specific procedures that are not part of standard medical care.
6. Subjects must have measurable neoplastic disease based on the iRECIST criteria
7. Subjects must have received as least 1 and no more than 2 prior systemic regimens for the treatment of advanced/metastatic NSCLC. Patients are required to have progressed following treatment with both platinum-based chemotherapy and an anti-PD-(L)1 antibody administered either sequentially or concurrently. A prior PD-1/PD-L1 inhibitor is, however, not required if there was prior exposure to targeted therapies for a driver mutation positive tumors (e.g. EGFR or ALK inhibitors).

Main Exclusion Criteria:

1. Subjects with active infection requiring treatment within 3 days of C1D1.
2. Subjects with other active neoplastic disease requiring concurrent anti-neoplastic treatment
3. Subjects with known, suspected or documented parenchymal brain metastases unless treated with surgery and/or radiation, with the subject neurologically stable and off pharmacologic doses of systemic glucocorticoids; subjects with leptomeningeal metastases are not eligible. Patients should have completed brain radiation for at least 14 days and be off steroids.
4. Active or previously documented autoimmune or inflammatory disorders such as, but not limited to rheumatoid arthritis, systemic lupus erythematosus, uveitis, ulcerative colitis, Crohn's syndrome, Wegener's syndrome, multiple sclerosis, myasthenia gravis, scleroderma and sarcoidosis. The following are exceptions to this criterion:

   * Vitiligo or psoriasis not requiring systemic treatment (within the last 2 years)
   * Subjects with endocrinopathies (e.g. following Hashimoto syndrome) stable on hormone replacement or do not require any therapy.
5. History of primary immunodeficiency
6. Subjects with a history or prior allogeneic organ transplant

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: From the first treatment to first CR or PR (estimated about 24 months)
Secondary outcomes:
measure: Disease Control Rate (DCR)
timeFrame: From the first administration of treatment till study completion (estimated about 24 months).
measure: Duration of Response (DOR)
timeFrame: estimated about 24 months.
measure: Progression-free Survival (PFS)
timeFrame: From the first administration of treatment to the date of first documentation of disease progression, or death due to any cause, whichever occurs first (estimated about 24 months).
measure: Overall Survival (OS)
timeFrame: estimated about 24 months.
measure: Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From the first administration of obinutuzumab pretreatment till study completion (estimated about 24 months).
Other outcomes:
Locations:
city: Daphne
country: United States
facility: NeoTX - 10307
state: Alabama
city: Scottsdale
country: United States
facility: NeoTX - 10302
state: Arizona
city: Tucson
country: United States
facility: NeoTX - 10303
state: Arizona
city: Lone Tree
country: United States
facility: NeoTX - 10306
state: Colorado
city: Minneapolis
country: United States
facility: NeoTX - 10304
state: Minnesota
city: Morristown
country: United States
facility: NeoTX - 10100
state: New Jersey
city: Austin
country: United States
facility: NeoTX - 10308
state: Texas
city: Dallas
country: United States
facility: NeoTX - 10309
state: Texas
city: El Paso
country: United States
facility: NeoTX - 10312
state: Texas
city: Tyler
country: United States
facility: NeoTX - 10310
state: Texas
city: Fairfax
country: United States
facility: NeoTX - 10311
state: Virginia
Study officials:
affiliation: NeoTX Therapeutics Ltd.
name: Ilana Lorber, MD
role: STUDY_DIRECTOR
References: