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

Non-small Cell Lung Cancer Clinical Trial

— NT-NAP-102-1  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04880863
• Other study ID #: NT-NAP-102-1
• Status: Completed
• Phase: Phase 2
• Start date: October 26, 2021
• Est. completion date: January 30, 2024

Study information

• Verified date: February 2024
• Source: NeoTX Therapeutics Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 38
• Est. completion date: January 30, 2024
• Est. primary completion date: January 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

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

Locations

Country	Name	City	State
United States	NeoTX - 10308	Austin	Texas
United States	NeoTX - 10309	Dallas	Texas
United States	NeoTX - 10307	Daphne	Alabama
United States	NeoTX - 10312	El Paso	Texas
United States	NeoTX - 10311	Fairfax	Virginia
United States	NeoTX - 10306	Lone Tree	Colorado
United States	NeoTX - 10304	Minneapolis	Minnesota
United States	NeoTX - 10100	Morristown	New Jersey
United States	NeoTX - 10302	Scottsdale	Arizona
United States	NeoTX - 10303	Tucson	Arizona
United States	NeoTX - 10310	Tyler	Texas

Sponsors (2)

Lead Sponsor	Collaborator
NeoTX Therapeutics Ltd.	Translational Drug Development

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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).
Secondary	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).
Secondary	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).
Secondary	Overall Survival (OS)	The time from first day of study drug treatment (obinutuzumab) to death for any cause	(estimated about 24 months).
Secondary	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).
Secondary	NAP blood levels over time	NAP concentration	From the first administration of NAP till study completion (estimated about 24 months).
Secondary	NAP immunogenicity	Change From Baseline in the titer of anti-drug antibodies (ADAs) to NAP.	From the first administration of NAP till study completion (estimated about 24 months).