NT-NAP-102-1: Naptumomab Estafenatox (NAP) in Combination With Docetaxel Following Obinutuzumab Pretreatment in Subjects With Checkpoint Inhibitor Pretreated Advanced or Metastatic NSCLC

Sponsor

NeoTX Therapeutics Ltd. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04880863

Collaborator

Translational Drug Development (Other)

Enrollment

Locations

Arm

26.1

Anticipated Duration (Months)

3.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Phase 2a Open-Label, Multicenter Trial of Naptumomab Estafenatox (NAP), on Days 1-4, in Combination with Docetaxel, on Day 5, Following Obinutuzumab Pretreatment, on Days -13 and -12. Treatment cycles will be 21 days in duration.

Condition or Disease	Intervention/Treatment	Phase
Non-small Cell Lung Cancer	Drug: NAP (Naptumomab estafenatox) Drug: Docetaxel Drug: Obinutuzumab	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

35 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention 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 in a daily dose of 10 μg/kg by IV bolus on Days 1 - 4 of each treatment cycle, followed by docetaxel, 75 mg/m2 on Day 5 of each treatment cycle. Treatment cycles will be 21 days in duration.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 each treatment cycle, followed by docetaxel, 75 mg/m2 on Day 5 of each treatment cycle. Treatment cycles will be 21 days in duration.

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jul 29, 2021

Anticipated Primary Completion Date :

Jun 1, 2023

Anticipated Study Completion Date :

Oct 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: NAP in combination with docetaxel following obinutuzumab pretreatment 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 each treatment cycle, followed by docetaxel, 75 mg/m2 on Day 5 of each treatment cycle.	Drug: 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 is linked to a Fab moiety recognizing a tumor-associated glycoprotein, 5T4. NAP is administered on Days 1-4 of each treatment cycle. Other Names: ABR-217620 Anyara Drug: Docetaxel Docetaxel is administered in combination with the study drug, NAP, on Day 5 of the treatment cycle. Other Names: Taxotere Drug: Obinutuzumab Obinutuzumab is administered as pre-medication on Day -13 and -12 of the first treatment cycle. Other Names: Gazyva

Arm

Intervention/Treatment

Experimental: NAP in combination with docetaxel following obinutuzumab pretreatment

Drug: 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 is linked to a Fab moiety recognizing a tumor-associated glycoprotein, 5T4. NAP is administered on Days 1-4 of each treatment cycle.

Other Names:

ABR-217620

Anyara

Drug: Docetaxel

Docetaxel is administered in combination with the study drug, NAP, on Day 5 of the treatment cycle.

Other Names:

Taxotere

Drug: Obinutuzumab

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

Other Names:

Gazyva

Outcome Measures

Primary Outcome Measures

Objective Response Rate (ORR) [From the first administration of obinutuzumab pretreatment to first CR or PR (estimated about 24 months)]
The proportion of subjects who achieve a best response of CR or PR per Response Evaluation in Solid Tumors (RECIST 1.1).

Secondary Outcome Measures

Disease Control Rate (DCR) [From the first administration of obinutuzumab pretreatment till study completion (estimated about 24 months).]
The proportion of subjects who achieve a best response of CR, PR or SD per Response Evaluation in Solid Tumors (RECIST 1.1).
Duration of Response (DOR) [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) [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).]
PFS per Response Evaluation in Solid Tumors (RECIST 1.1)
6-month PFS rates [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).]
PFS per Response Evaluation in Solid Tumors (RECIST 1.1)
12-month PFS rates [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).]
PFS per Response Evaluation in Solid Tumors (RECIST 1.1)
Overall Survival (OS) [From the first administration of obinutuzumab pretreatment to death from any cause (estimated about 24 months).]
Treatment-Emergent Adverse Events (TEAEs) [From the first administration of obinutuzumab pretreatment till study completion (estimated about 24 months).]
Number of subjects with treatment-related adverse events as assessed by CTCAE v5.0
NAP blood levels over time [From the first administration of NAP till study completion (estimated about 24 months).]
NAP concentration
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).]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 RECIST 1.1 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).

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 per exclusion criteria 7.
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	NeoTX - 10307	Daphne	Alabama	United States	36526
2	NeoTX - 10302	Scottsdale	Arizona	United States	85258
3	NeoTX - 10303	Tucson	Arizona	United States	85711
4	NeoTX - 10306	Lone Tree	Colorado	United States	80124
5	NeoTX - 10304	Minneapolis	Minnesota	United States	55404
6	NeoTX - 10308	Austin	Texas	United States	78745
7	NeoTX - 10309	Dallas	Texas	United States	75246
8	NeoTX - 10312	El Paso	Texas	United States	79902
9	NeoTX - 10310	Tyler	Texas	United States	75702
10	NeoTX - 10311	Fairfax	Virginia	United States	22205