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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: NAP (Naptumomab estafenatox)
* Drug: Docetaxel
* Drug: Obinutuzumab


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Subjects must be at least 18 years of age Subjects must have histologically and/or cytologically confirmed NSCLC Subjects must have incurable (advanced or metastatic) disease at the time of enrolment Subjects must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 Subjects must provide signed informed consent prior to any study specific procedures that are not part of standard medical care. Subjects must have measurable neoplastic disease based on the iRECIST criteria 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: Subjects with active infection requiring treatment within 3 days of C1D1. Subjects with other active neoplastic disease requiring concurrent anti-neoplastic treatment 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. 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. History of primary immunodeficiency Subjects with a history or prior allogeneic organ transplant

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Subjects will 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 will be 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 will be 21 days in duration. Starting cycle 7, NAP at a higher dose will be 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 will be of 28 days of duration.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NAP in combination with docetaxel following obinutuzumab pretreatment<br>Subjects will 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 will be administered in a daily dose of 10 μg/kg by IV bolus on Days 1 - 4 of treatment cycles 1-6, followed by docetaxel, 75 mg/m2 on Day 5. Treatment cycles with the combination NAP/docetaxel will be 21 days in duration. Starting cycle 7, NAP at a higher dose of 15 μg/kg will be 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 will be of 28 days of duration. | Drug: NAP (Naptumomab estafenatox)<br>* 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 is linked to a Fab moiety recognizing a tumor-associated glycoprotein, 5T4. NAP will be administered in 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 will be administered on Day 1.<br>* Other names: Anyara;Drug: Docetaxel<br>* Docetaxel is administered in combination with the study drug, NAP, on Day 5 of the treatment cycles 1-6. Starting cycle 7, Docetaxel will be administered in combination with the study drug, NAP, on Day 2.<br>* Other names: Taxotere;Drug: Obinutuzumab<br>* Obinutuzumab is administered as pre-medication on Day -13 and -12 of the first treatment cycle.<br>* Other names: Gazyva;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | The proportion of subjects who achieve a best response of CR or PR per Response Evaluation in Solid Tumors (iRECIST). | From the first administration of obinutuzumab pretreatment to first CR or PR (estimated about 24 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Control Rate (DCR) | The proportion of subjects who achieve a best response of CR, PR or SD per Response Evaluation in Solid Tumors (iRECIST). | From the first administration of obinutuzumab pretreatment till study completion (estimated about 24 months). | 
| Duration of Response (DOR) | Duration from first documentation of CR or PR (whichever occurs first) after the first administration of obinutuzumab pretreatment until death or progressive disease (PD) | (estimated about 24 months). | 
| Progression-free survival (PFS) | PFS per Response Evaluation in Solid Tumors (iRECIST) | From the first administration of obinutuzumab pretreatment to the date of first documentation of disease progression, or death due to any cause, whichever occurs first (estimated about 24 months). | 
| 6-month PFS rates | PFS per Response Evaluation in Solid Tumors (iRECIST) | From the first administration of obinutuzumab pretreatment to the date of first documentation of disease progression, or death due to any cause, whichever occurs first (up to 6 months). | 
| 12-month PFS rates | PFS per Response Evaluation in Solid Tumors (iRECIST) | From the first administration of obinutuzumab pretreatment to the date of first documentation of disease progression, or death due to any cause, whichever occurs first (up to 12 months). | 
| Overall Survival (OS) | The time from first day of study drug treatment (obinutuzumab) to death for any cause | (estimated about 24 months). | 
| Treatment-Emergent Adverse Events (TEAEs) | Number of subjects with treatment-related adverse events as assessed by CTCAE v5.0 | From the first administration of obinutuzumab pretreatment till study completion (estimated about 24 months). | 
| NAP blood levels over time | NAP concentration | From the first administration of NAP till study completion (estimated about 24 months). | 
| NAP immunogenicity | Change From Baseline in the titer of anti-drug antibodies (ADAs) and human anti-mouse antibodies (HAMA) to NAP. | From the first administration of NAP till study completion (estimated about 24 months). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced, Metastatic, Non small cell lung cancer, EGFR, ALK, Docetaxel, Naptumomab estafenatox, Obinutuzumab, NAP