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

NeoTX Therapeutics

Status and phase: Completed; Phase 2

Conditions: Non-small Cell Lung Cancer

Treatments: Drug: NAP (Naptumomab estafenatox); Drug: Obinutuzumab; Drug: Docetaxel

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04880863

NT-NAP-102-1

Details and patient eligibility

About

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.

Full 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.

Enrollment: 38 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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38 participants in 1 patient group

NAP in combination with docetaxel following obinutuzumab pretreatment

Experimental group

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.

Treatment:

Drug: Docetaxel

Drug: Obinutuzumab

Drug: NAP (Naptumomab estafenatox)