NAP in Combination With Docetaxel Following Obinutuzumab Pretreatment in Subjects With Checkpoint Inhibitor Pretreated Advanced or Metastatic NSCLC

NCT ID: NCT04880863

Last Updated: 2025-03-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-26
• Study Completion Date: 2024-01-30

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.

Conditions

Non-small Cell Lung Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

NAP in combination with docetaxel following obinutuzumab pretreatment

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.

Group Type: EXPERIMENTAL

NAP (Naptumomab estafenatox)

Intervention Type: DRUG

Naptumomab estafenatox (NAP; ABR-217620) is a recombinant fusion protein consisting of a chimeric staphylococcal enterotoxin A/E (SEA/SEE) superantigen with several additional substitutions that are linked to a Fab moiety recognizing a tumor-associated glycoprotein, 5T4. NAP is administered at a dose of 10 μg/kg/day by IV bolus on Days 1 - 4 of treatment cycles 1-6. Starting cycle 7, NAP at a higher dose of 15 μg/kg is administered on Day 1.

Docetaxel

Intervention Type: DRUG

Docetaxel is administered in combination with the study drug, NAP, on Day 5 of the treatment cycles 1-6. Starting cycle 7, Docetaxel is administered in combination with the study drug, NAP, on Day 2.

Obinutuzumab

Intervention Type: DRUG

Obinutuzumab is administered as pre-medication on Day -13 and -12 of the first treatment cycle.

Interventions

NAP (Naptumomab estafenatox)

Naptumomab estafenatox (NAP; ABR-217620) is a recombinant fusion protein consisting of a chimeric staphylococcal enterotoxin A/E (SEA/SEE) superantigen with several additional substitutions that are linked to a Fab moiety recognizing a tumor-associated glycoprotein, 5T4. NAP is administered at a dose of 10 μg/kg/day by IV bolus on Days 1 - 4 of treatment cycles 1-6. Starting cycle 7, NAP at a higher dose of 15 μg/kg is administered on Day 1.

Intervention Type: DRUG

Docetaxel

Docetaxel is administered in combination with the study drug, NAP, on Day 5 of the treatment cycles 1-6. Starting cycle 7, Docetaxel is administered in combination with the study drug, NAP, on Day 2.

Intervention Type: DRUG

Obinutuzumab

Obinutuzumab is administered as pre-medication on Day -13 and -12 of the first treatment cycle.

Intervention Type: DRUG

Other Intervention Names

ABR-217620; Anyara; Taxotere; Gazyva

Eligibility Criteria

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).

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Translational Drug Development

OTHER

Sponsor Role: collaborator

NeoTX Therapeutics Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ilana Lorber, MD

Role: STUDY_DIRECTOR

NeoTX Therapeutics Ltd.

Locations

NeoTX - 10307

Daphne, Alabama, United States

NeoTX - 10302

Scottsdale, Arizona, United States

NeoTX - 10303

Tucson, Arizona, United States

NeoTX - 10306

Lone Tree, Colorado, United States

NeoTX - 10304

Minneapolis, Minnesota, United States

NeoTX - 10100

Morristown, New Jersey, United States

NeoTX - 10308

Austin, Texas, United States

NeoTX - 10309

Dallas, Texas, United States

NeoTX - 10312

El Paso, Texas, United States

NeoTX - 10310

Tyler, Texas, United States

NeoTX - 10311

Fairfax, Virginia, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NT-NAP-102-1

Identifier Type: -

Identifier Source: org_study_id