NP137 Clinical and Biological Activities Assessment in Patients With Advanced/Metastatic Solid Tumors Treated by Standard Anti PD-1/PD-L1 Immunotherapies

NCT05605496 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: ET21-296EU number
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 5

Brief Summary

This study is a multicenter, open-label, proof-of-concept study aiming to assess the clinical and biological impact of NP137 when added to standard PD-1/PD-L1 blockade therapy in 3 independent cohorts of advanced or metastatic solid tumors with various sensitivity to anti-PD-1/PD-L1:

• Cohort 1 \[Stable Disease\]: Patients with a radiological documentation of SD according to RECIST V1.1 criteria following at least 12 weeks under standard anti PD-1/PD-L1 therapy. Note: This treatment arm closed on 27/09/2024 due to non-feasibility.
• Cohort 2 \[primary refractory\]: Patients with documented radiological PD or short-term SD (\< 6months) according to RECIST V1.1 but with clinical benefit under PD-1/PD-L1 standard therapy.
• Cohort 3 \[secondary refractory\]: Patients with documented radiological PD following an initial Objective Response or long-term SD (i.e. ≥6 months) according to RECIST V1.1, with clinical benefit under standard PD-1/PD-L1.

Conditions

Metastatic Solid Tumors; Advanced Solid Tumors

Keywords

Solid Tumors; NP137; anti-PD1/PDL1; Stable disease; Primary refractory; Secondary Refractory; Netrin-1; monoclonal antibody

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate (ORR-12W)

  Cohort 1 (SD): rate of patients with CR or PR according to RECIST V1.1 after the first 12 weeks of the NP137 as add on therapy.

  12 weeks

• Progression Free Rate at 12 weeks (PFR-12W)

  Cohort 2 \& 3 (primary and secondary refractory refractory): defined as the proportion of patients without documented disease progression according to RECIST V1.1 or documented clinical disease progression after the first 12 weeks of the NP137 as add on therapy.

  12 weeks

Secondary Outcomes (4)

• Objective Response Rate (ORR-12W)

  12 weeks

• Time to objective response (ToR)

  Every 12 weeks, up to 52 weeks

• Duration of Response (DoR)

  Every 12 weeks, up to 52 weeks

• Safety profile

  from the date of first intake of study drug until 90 days after study drug discontinuation or at time of initiation of a new anti-cancer treatment

Other Outcomes (4)

• Epithelial-mesenchymal transition (EMT) score evolution under treatment

  before first adminitration of NP137, then after 6 weeks of treatment and in case of relapse

• Modulation of the tumoral microenvironment

  before first adminitration of NP137, then after 6 weeks of treatment and in case of relapse

• Netrin-1 and UNC5B expression

  before first adminitration of NP137, then, after 6 weeks of treatment and in case of relapse

Study Arms (3)

Stable Disease

EXPERIMENTAL

Patients with a radiological documentation of SD according to RECIST V1.1 criteria following at least 12 weeks under standard PD-1/PD-L1 therapy. The initial evidence of SD is to be confirmed by a second assessment, no less than 4 weeks from the date of the first documented SD. Note : This treatment arm closed on 27/09/2024 due to non-feasibility.

Drug: NP137; Drug: anti-PD-1/PD-L1

Primary refractory

EXPERIMENTAL

Patients with documented radiological PD or short-term SD (\< 6months) according to RECIST V1.1 but with clinical benefit under PD-1/PD-L1 standard therapy.

Drug: NP137; Drug: anti-PD-1/PD-L1

Secondary refractory

EXPERIMENTAL

Patients with documented radiological PD following an initial Objective Response or long-term SD (i.e. ≥6 months) according to RECIST V1.1, with clinical benefit under standard PD-1/PD-L1.

Drug: NP137; Drug: anti-PD-1/PD-L1

Interventions

NP137 DRUG

IV infusion, 14mg/kg, Q3W

Primary refractory; Secondary refractory; Stable Disease

anti-PD-1/PD-L1 DRUG

IV infusion, Q3W or Q6W anti-PD1/PDL1 are standard treatments and are prepared and administred as per respective SmPC and institutional practice.

Primary refractory; Secondary refractory; Stable Disease

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• I1. Male or female patients aged ≥ 18 years at time of inform consent signature.
• I2. Patient with histologically confirmed locally advanced / metastatic solid tumors of any histological types
• I3. Patients treated with standard anti-PD-1/PD-L1 (e.g. pembrolizumab, atezolizumab, or any other ICI to be approved and reimbursed in France during the course of this trial, with a Q3W or Q6W schedule, either as monotherapy or in combination with chemotherapies according to their approved label). A positive list of eligible solid tumour types together with the associated anti-PD-1/PD-L1 standard therapy approved for each indication is provided in appendix 7. For any pathology not listed in this appendix but for which an anti-PD-1/PD-L1 has newly obtained a MA and is now reiumbursed in France, please refer to the section 0 of this protocol) and meet the following criteria :
• I3a. Cohort 1: Patient with RECIST 1.1.-defined SD under at least 12 weeks anti-PD-1/PD-L1. The initial evidence of SD is to be confirmed by a second assessment, no less than 4 weeks from the date of the first documented SD. Stable disease must be the best response observed since initiation of anti-PD-1/PD-L1 standard therapy or induction phase.
• I3b. Cohort 2: Patient with RECIST 1.1-defined PD under anti-PD-1/PD-L1 or short-term SD i.e. \< 6 months as best response under anti-PD-1/PD-L1.
• I3c. Cohort 3: Patients with RECIST 1.1-defined PD under anti-PD1/PD-L1 after initial objective response (CR or PR) or long-term benefit i.e. SD lasting at least 6 months as per RECIST V1.1
• Note 1 : For patients treated with an anti-PD-1/ PD-L1 previously combined to another anti-cancer agents of any type (including but not limited to chemotherapy/ other immunotherapy/ biological -or targeted agents) theseagents must be stopped 2 weeks or 5\* t ½ whichever is shorter before C1D1 while anti-PD1 or anti PDL1 is continued according to Market Authorisation.
• I4. Refractory cohorts: To be eligible in these cohorts, patients must meet all the following criteria:
• Evidence of clinical benefit according to investigator assessment. The assessment of clinical benefit should be balanced by clinical judgment as to whether the patient is clinically deteriorating and unlikely to receive any benefit from continued ICI treatment.
• Absence of symptoms and signs (including laboratory values, such as new or worsening hypercalcemia) indicating unequivocal progression of disease,
• Absence of decline in ECOG PS that can be attributed to disease progression,
• Absence of tumor progression at critical anatomical sites (e.g., leptomeningeal disease) that cannot be managed by protocol-allowed medical interventions.
• No ongoing clinically significant AE related to ICI.
• I5. Patient with of at least one lesion measurable and evaluable as per RECIST V1.1 according to central imaging review before C1D1. Tumour lesions located in a previously irradiated area, or in an area subjected to other locoregional therapy, cannot be considered as measurable/evlaluable unless there has been a documentation of progression in the lesion.
• I6. Availability of a representative archival tumor sample in formalin-fixed paraffin embedded (FFPE) block (primary tumor or metastasis) or newly obtained core or excisional biopsy of a tumor lesion together with an associated pathology report.

You may not qualify if:

• E1. Patients eligible to curative treatment E2. For refractory cohorts: patients eligible to standard treatment with documented proof of activity in the tumor type or to other therapeutic options (approved or investigational) with documented evidence of clinical activity.
• E4. Patient with any history of CTCAE Grade 4 irAEs under anti-PD-1/PD-L1 treatment or any history of CTCAE Grade 3 requiring steroid treatment (\>10 mg/day prednisone or equivalent dose) for \>12 weeks or CTCAE Grade 2 pneumonitis regardless of steroid treatment.
• E5. History of severe (≥ Grade 3) allergic anaphylactic reactions to one of the components of NP137, standard ICI, premedication and/or any of their excipients.
• E6. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
• E7. Has a known additional malignancy that is progressing or has required active treatment within the past 2 years.
• Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
• E8. Prior therapy or needs to be treated with a forbidden concomitant/concurrent therapies/procedures including:
• Any investigational agent or have used an investigational device. Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 2 weeks or 5\* ½ whichever is shorter after the last dose of the previous investigational agent.
• Radiotherapy within 4 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.Palliative radiation (≤ 2 weeks of radiotherapy) to non-CNS disease and on non-target lesion is allowed.
• Major surgery within 4 weeks of start of study treatment. Participants must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment, C1D1.
• Anti-cancer treatment other than those specified in the protocol i.e. standard anti-PD1/PDL1
• Live or live-attenuated vaccine within 30 days prior to the first dose of study treatments. Note: killed are allowed.
• Immunosuppressive medication within 2 weeks with the exceptions of intranasal, topical and inhaled corticosteroids or systemic corticosteroids at doses which are not to exceed 10 mg/day of prednisone, or equivalent doses of another corticosteroid.
• E9. Have a history of autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
• History of autoimmune disease which include but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis with the following exceptions:

Sponsors & Collaborators

• Centre Leon Berard: lead
• NETRIS Pharma: collaborator

Study Sites (5)

Centre Léon Bérard

Lyon, 69008, France

Location

Centre Antoine Lacassagne

Nice, 06189, France

Location

Institut Curie

Paris, 75005, France

Location

Institut de Cancérologie Strasbourg Europe (ICANS)

Strasbourg, 67033, France

Location

Institut Claudius Regaud (IUCT Oncopole)

Toulouse, 31059, France

Location

MeSH Terms

Interventions

netrin-1 inhibitor NP137

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The 3 cohorts of patients will be conducted and analyzed independently. The sample size calculation will use an adaptive Simon 2-stage design based on the strategy developed by Lin and Shih (Biometrics 2004). This method allows checking the result at the first stage, adjusting the power and success rate if necessary, and adapting the decision rule accordingly.

Study Record Dates

• First Submitted: October 31, 2022
• First Posted: November 4, 2022
• Study Start: January 6, 2023
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: April 24, 2026

Record last verified: 2026-04

Locations

FR (5)