Precision Immuno-Oncology for advanced Non-small cell lung cancer patients with PD-1 ICI Resistance (PIONeeR clinical study)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Regional De Marseille

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

8 Oct 2019 → 11 Aug 2025

Decision date (initial)

2024-09-25

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Recherche Hospitalo-Universitaire en Santé 2016

External identifiers

EU CT number

2024-515532-72-00

EudraCT number

2018-000914-39

ClinicalTrials.gov

NCT03833440

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy, Pharmacokinetic

To assess anti tumor activity of three immune experimental strategies
(combo with PDL1 inhibitor MEDI4736 - Durvalumab) compared to
docetaxel alone, the standard chemotherapy line, in advanced NSCLC
patients progressing on standard 2nd to 3rd line PD-1/PDL1monotherapy
treatment.

Secondary objectives 5

1. Safety and tolerability of each arm of treatment
2. PharmacoKinetics / PharmacoDynamics parameters of each drug
3. Overall Response Rate
4. Overall & Progression Free Survival
5. Immunogenicity of the injected drugs

Conditions and MedDRA coding

non small cell lung cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Able and willing to give a signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent obtained from the patient prior to performing any protocol-related procedures, including screening evaluations.
2. Age > 18 years
3. Patients must have histologically confirmed diagnosis of advanced (proven advanced stage) or recurrent NSCLC, (both squamous and nonsquamous pathologies are accepted; patients with a mixed NSCLC and SCLC component are ineligible)
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
5. Body weight >35kg
6. Patients with evidence of radiological progression after more than 6 and less than 18 weeks of a registered second or third line PD1 or PD-L1 inhibitor in monotherapy (to include , Nivolumab, Pembrolizumab, Atezolizumab) Patients who have received immunotherapy in the maintenance setting can only have had one prior regimen containing PD-1/L1 inhibitor. No intervening treatment between the immunotherapy and entry into this study is permitted. Atezolizumab)
7. Patients with known actionable molecular alteration (EGFR activating mutation, ALK rearrangement, ROS1 rearrangement) should have received a commercially available specific inhibitor
8. As of Week 1 Day 1, subjects with central nervous system (CNS) metastases must have been treated and must be asymptomatic and meet the following: a. No concurrent treatment, inclusive of but not limited to surgery, radiation, and/or corticosteroids b. At least 14 days after CNS treatment, clinically stable with no symptoms of CNS metastasis or sequelae of radiation and at least 14 days since last dose of corticosteroids NOTE: Subjects with clinical symptoms or cord compression or with leptomeningeal disease are excluded from the study
9. Adequate organ and bone marrow function as defined below: - Haemoglobin ≥9.0 g/dL(transfusion to achieve this level is not permitted within 2 weeks of first study drug administration) - Absolute neutrophil count (ANC) 1.5 x (> 1500 per mm3) - Platelet count ≥100 x 109/L (>100,000 per mm3) - Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome , who will be allowed only in consultation with their physician. - Normal thyroid function, subclinical hypothyroidism (TSH < 10 mIU/mL) or have controlled thyroid disorder - AST (SGOT) and/ALT (SGPT) ≤2.5 x institutional upper limit of normal with total bilirubin < 1 x ULN unless liver metastases are present, in which case it must be ≤5x ULN, or AST(SGOT) and ALT (SGPT) ≤≤ 1 ULN with total bilirubin > 1 x ULN to ≤ 1.5 ULN
10. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: - Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy). - Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
11. Women must not be breastfeeding
12. Women and men of reproductive potential must agree to use highly effective(<1% failure rate)contraception. This applies for the period between signing of the informed consent and 6 months after the last administration of study drug . These procedures should be documented in source documents. The investigator or a designated associate is requested to advise the subject on how to achieve highly effective birth control. Highly effective contraception (<1% failure rate): - Established use of injected or implanted hormonal methods of contraception - Placement of certain intrauterine devices (IUD) or intrauterine systems (IUS) - Hysterectomy, or vasectomy of the partner (provided that partner is the sole sexual partner of the woman of childbearing potential trial participant and that the vasectomized partner has received medical assessment of the surgical success) In addition, the use of condoms for patients or their partners is required - Total abstinence

Exclusion criteria 16

1. Individuals deprived of liberty or placed under the authority of a tutor
2. Patient unable to understand, read and/or sign an informed consent
3. Absence of a measurable target lesion according to RECIST criteria 1.1
4. Any symptomatic or untreated brain metastasis
5. Any previous treatment with Docetaxel
6. Prior randomisation or treatment with durvalumab, Ceralasertib, Savolitinib , Oleclumab, Monalizumab
7. Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
8. Any previous treatment with a PD1 or PD-L1 inhibitor with the following events: - Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy. - All AEs while receiving prior immunotherapy must have completely resolved or resolved to baseline prior to screening for this study. - Must not have experienced a ≥Grade 3 immune related AE or an immune related neurologic or ocular AE of any grade while receiving prior immunotherapy. NOTE: Patients with endocrine AE of ≤Grade 2 are permitted to be enrolled if they are stably maintained on appropriate replacement therapy and are asymptomatic. - Must not have required the use of additional immunosuppression other than corticosteroids for the management of an AE, not have experienced recurrence of an AE if re-challenged, and not currently require maintenance doses of > 10 mg prednisone or equivalent per day - No intervening treatment between progression on ICI and entry into this study
9. Receipt of the last dose of, immunotherapy, ≤21 days prior to the first dose of study drug the washout is 30 days or 5 half-lives, whichever is longer, Patients are not permitted to have received more than one prior line of immunotherapy
10. The patient can receive a stable dose of bisphosphonates or denosumab for bone metastases, before and during the study as long as these were started at least 5 days prior to the study treatment
11. Current or prior use of steroids or other immunosuppressive medication within 28 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which do not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. The following are exceptions to this criterion: - Intranasal, inhaled, topical steroids, eyes drops or local steroid injections (e.g., intra articular injection) - Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent - Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
12. Any unresolved toxicity NCI CTCAE v5.0 Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria - Patients with Grade ≥2 neuropathy will be evaluated on a case-bycase basis after consultation with the Study Physician. - Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or other IMP on study may be included only after consultation with the Study Physician. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment is not allowed. Concurrent use of hormonal therapy for noncancer- related conditions (e.g., hormone replacement therapy) is acceptable
13. Palliative radiotherapy (to a non target lesion) must have been completed at least 7 r days before Cycle 1 Day 1 (with the exception of patients receiving radiation to more than 30% of the bone marrow or with a wide field of radiation who must have completed treatment within 28 days of the first dose of study treatment).
14. Major surgical procedure within 28 days prior to the first dose of IP : patients must have recovered from any effects of any major surgery Note: Local surgery and other procedures (radiotherapy) of isolated lesions for palliative intent is acceptable
15. History of allogenic organ or stem cell transplantation
16. Active or prior documented autoimmune related inflammatory disorders treated with systemic immunosuppressive drugs within the last 3 months or history of clinically severe auto-immune disease(including inflammatory bowel disease, diverticulitis, systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome) The following are exceptions to this criterion: - Patients with stable diabetes type 1, resolved childhood asthma/atopy, Sjorgren syndrome, controlled allergic rhinitis are allowed to participate - Patients with vitiligo or alopecia - Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement - Any chronic skin condition that does not require systemic therapy - Patients without active disease in the last 3 years may be included but only after consultation with the study physician - Patients with celiac disease controlled by diet alone

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. the determination of 12-week Disease Control Rate (DCR) assessed in each arm of treatment

Secondary endpoints 2

1. the proportion of patients with complete response (CR) or partial response (PR) as best overall response over the treatment period.
2. The Progression-free survival

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 7

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Regional De Marseille

Sponsor organisation

Centre Hospitalier Regional De Marseille

Address

80 Rue Brochier

City

Marseille

Postcode

13005

Country

France

Scientific contact point

Organisation

Centre Hospitalier Regional De Marseille

Contact name

INVESTIGATOR COORDINATOR

Public contact point

Organisation

Centre Hospitalier Regional De Marseille

Contact name

project manager

Third parties 1

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications