A multicenter phase 1/2 study of OSE-279, a PD-1 blocking monoclonal antibody, in subjects with advanced solid tumors or lymphomas

Overview

Sponsor-declared trial summary

Key facts

Sponsor

OSE Immunotherapeutics

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

5 Dec 2022 → ongoing

Decision date (initial)

2024-11-06

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-514826-22-00

EudraCT number

2022-001136-28

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

Part A: To determine the Maximum Tolerated Dose (MTD) and/or the Recommended Phase 2 Doses (RP2D) when administered as single IV infusion on every 3 or 6 weeks.
Part B: To evaluate the safety and tolerability of the combination OSE-279/OSE2101.
Part C: To assess the antitumor activity of OSE-279 in combination with OSE2101 versus 0SE-279 in terms of overall response rate (ORR) as assessed locally, in patients with 1st line metastatic (stage IV) NSCLC.

Secondary objectives 7

1. Part A: To assess the antitumor activity in terms of Objective Response Rate (ORR), Disease Control Rate (DCR), Time to Response (TTR), Duration of Objective Response (DOR), Progression-Free Survival (PFS), DCR at 12 weeks and Overall Survival (OS)
2. Part A: To evaluate the safety profile.
3. Part A: To evaluate the pharmacokinetic (PK) profile of OSE-279.
4. Part A: To evaluate immunogenicity (anti-drug antibodies or ADA) of OSE-279.
5. Part B: To preliminary determine the antitumor activity of the combination (ORR, DCR, DOR, TTR, DCR at 12 weeks and 24 weeks, PFS, OS and OS at 12 months).
6. Part C: To further assess the efficacy of the combination of OSE-279/OSE2101 versus OSE-279 with respect to DCR,TTR, DOR, PFS, DCR at 12 weeks and 24 weeks, OS and OS rate at 12 months.
7. Part C: To further evaluate the safety profile of both treatment groups.

Conditions and MedDRA coding

Part A: Patients with advanced solid tumors or lymphomas.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Male or female adult patients (≥ 18 years).
2. Signed and dated informed consent form (ICF) prior to any trial-specific procedures. Patients should be able and willing to comply with study visits and procedures as per protocol.
3. ECOG performance status 0-1.
4. Part A: Tumor type: a. advanced solid tumors or lymphomas for which an anti PD-1/PD-L1 has shown efficacy (e.g., with high microsatellite instability or MSI-H) but is not available in the center/country (no marketing authorization, no reimbursement, no early access program, etc.) or; b. rare tumors with reported significant activity of anti-PD-1 (e.g., Tertiary Lymphoid Structures positive or TLS+ sarcomas, alveolar soft part sarcomas, etc.), or; c.PD-L1 positive tumors.
5. Part A: Prior treatment with at least one line of systemic therapy and no standard of care available.
6. Part A: Evaluable or measurable disease according to RECIST 1.1/RECIL.
7. Adequate organ function: a. Bone marrow: neutrophils ≥ 1.5 x 10^9/L, hemoglobin ≥ 90 g/L, platelets ≥ 100 x 10^9/L; b. Renal function: serum creatinine ≤ 1.5 ULN or CKD-EPI creatinine clearance ≥ 30 mL/min; c. Liver function: AST and ALT ≤ 3 ULN, bilirubin ≤ 1.5 ULN. In case of liver metastasis: AST and ALT ≤ 5 ULN. For patients with Gilbert’s syndrome total bilirubin ≤ 3 ULN or direct bilirubin ≤ 1.5 ULN.
8. Patients must be affiliated to a social security system or an equivalent system, if applicable as per local regulations.
9. Part B and C: Patients expressing HLA-A2 phenotype on blood sample performed by an experienced laboratory using a validated test.(PCR or NGS); Additional patients HLA-A2 negative will be included in PART C.
10. Part B and C: Tumor type: a.Histologically or cytologically documented Stage IV squamous or non-squamous NSCLC not eligible for definite surgery or radiation, which does not have EGFR sensitizing (activating) mutation or ALK and ROS1 gene alterations eligible for targeted therapy or other mutations for which an approved therapy exists in 1st line metastatic setting (i.e.; KRAS G12C, RET, MET SKIP14, BRAFV600E mutations); b. Documented PD-L1 expression by TPS ≥ 50% by local testing.
11. Part B and C: Patients must not have received prior systemic therapy including immunotherapy in the first-line metastatic setting; Completion of treatment with chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as therapy was completed at least 6 months prior to the diagnosis of metastatic disease.
12. Part B and C: Patients with at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

Exclusion criteria 22

1. Patient eligible to surgical resection or another approved therapeutic regimen known to provide clinical benefit.
2. Patient previously treated with an approved or investigational anti-PD-1/PD-L1.
3. Patient with active autoimmune disease or a documented history of autoimmune disease requiring systemic treatment (i.e., corticosteroids or immunosuppressive drugs); except autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone, controlled hypophysitis, controlled Type 1 diabetes mellitus on a stable insulin regimen, vitiligo, resolved childhood asthma/atopy, alopecia, or any chronic skin condition not requiring systemic therapy.
4. Patient participating in another clinical trial with a medicinal product.
5. Patients who have not recovered from adverse events (i.e., > Grade 1 according to CTCAE v5.0) due to prior treatment with anti-cancer agents with exception of Grade 2 neuropathy or any Grade alopecia. Lab values must be within the limits presented in criterion I-7.
6. Patients with known additional malignancy progressing or requiring active treatment. Basal cell carcinoma, squamous cell carcinoma of the skin, or in situ cervical cancer are not non-inclusion criteria.
7. Patients with known active central nervous system metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to C1D1 and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids (at doses higher than 10 mg/day of methylprednisolone or equivalent) for at least 4 weeks prior C1D1.
8. Patients with active or history of non-infectious pneumonitis requiring steroids, or interstitial lung disease.
9. Patients with a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient’s participation for the full duration of the study.
10. Patients with a history of uncontrolled or symptomatic, clinically significant cardiovascular disease: stroke, myocardial infarction, angina pectoris, arrhythmias, congestive heart failure (NYHA Class >2), or myocarditis within 6 months prior to first study drug administration.
11. Patient with organ(s) transplant including hematopoietic stem cell allograft.
12. Patients receiving or to be treated during the treatment period with one of the following forbidden treatments: a. Any anti-cancer systemic chemotherapy, targeted therapy or biological therapy including any immunotherapy not mentioned in this protocol. Washout prior to screening: chemotherapy: 3 weeks (6 weeks for nitrosourea), TKi or other small molecules: 2 weeks or 5 half-lives whichever is shortest, mAb: 4 week; b. Radiation therapy (washout prior to screening: 7 days prior to Cycle 1). Note: Radiation therapy to a symptomatic solitary non target lesion or to the brain may be allowed after consultation with Sponsor; c. Live vaccines. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, tuberculosis (BCG), and typhoid (oral) vaccines. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed; d. Recent major surgery within the previous 3 months; e. Systemic corticosteroids for any purpose other than to modulate symptoms from an event of clinical interest of suspected immunologic etiology. The use of physiologic doses of corticosteroids may be approved after consultation with the Sponsor. Immunosuppressive agents such as steroids should be tapered off before initiation of study treatment (except low-dose up to a total dose equivalent to prednisolone 10 mg/day).
13. Patients with hypersensitivity to OSE-279/OSE2101 or any of its excipients.
14. Patients with active tuberculosis (Mycobacterium tuberculosis).
15. Patients with: a. Active hepatitis B (defined as Hbs Ag+ and/or anti-HBc+ and HBV DNA+); b. Active hepatitis C (anti-HCV+ and HCV RNA+); c. Active HIV infection: HIV+ patients on highly active antiretroviral therapy (HAART) are eligible if PCR for HIV is negative at screening; d. Presence of signs/symptoms suggestive of active infection (including COVID-19 infection).
16. Patients with known psychiatric or substance abuse disorders that would interfere their ability to comply with protocol requirements.
17. WOCBP and men participating in the study (and their partners) must agree to follow the precautions to avoid gestational problems, by using highly efficient contraception throughout the study and until 8 months after the last administration of investigational treatment based on CTFG guidance. In addition, during this study period men should use condoms and avoid semen donation.
18. Women who are pregnant or breast-feeding or women/men expecting to conceive children within the projected duration of the trial, starting with the screening visit through 8 months after the last dose of trial treatment.
19. Vulnerable persons, if applicable as per local regulations, such as individuals under the protection of a legal guardian, pregnant or breastfeeding women, persons in custody by judicial or administrative decision, persons under psychiatric care without consent, persons admitted in a healthcare facility or social institution not for research purposes, minors, individuals unable to state their consent.
20. Part B and C: Small-cell lung cancer/mixed NSCLC with small cell component or other neuroendocrine lung cancers (typical and atypical carcinoids, large-cell neuroendocrine carcinomas).
21. Part B and C: Patients with hypersensitivity to OSE-279 or OSE-2101 or any of one of their excipients.
22. Part B and C: Patients previously treated with anti-PD-L2, anti-CD137, or anti-Cytotoxic T-Lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Part A: Occurrence of dose limiting toxicity (DLT) for MTD determination and/or RP2D.
2. Part B: Occurrence of dose limiting toxicity (DLT) where DLT observation period is defined as the first 6 weeks after receiving the first injections of OSE-279 and of OSE2101.
3. Part C: ORR: Complete Response (CR) and Partial Response (PR) rate.

Secondary endpoints 6

1. Part A: Efficacy (Objective Response Rate (ORR): Complete Response (CR) and Partial Response (PR) rate ; Disease Control Rate (DCR): CR, PR and Stable Disease (SD) rate; • Time to response (TTR); • Duration of Objective Response (DOR); Progression Free Survival (PFS); DCR (CR+PR+SD) at 12 weeks; Overall Survival (OS)).
2. Part A: Pharmacokinetics and Pharmacodynamics (OSE-279 Pharmacokinetic parameters; Detection of anti-OSE-279 antibodies).
3. Part B: Efficacy (ORR: Complete Response (CR) and Partial Response (PR) rate; DCR: CR, PR and Stable Disease (SD) rate; Time to response (TTR); Duration of Objective Response (DOR); • Progression Free Survival (PFS); DCR (CR+PR+SD) at 12 weeks and 24 weeks; Overall Survival (OS); OS rate at 12 months).
4. Part B: Safety (Nature, incidence and severity of TEAE (including DLT and AE of special Interest (AESI)), of SAE, SUSARs graded according to CTCAE grading v5.0).
5. Part C: Efficacy (DCR: CR, PR and Stable Disease (SD) rate; Time to response (TTR); Duration of Objective Response (DOR); • Progression Free Survival (PFS); DCR (CR+PR+SD) at 12 weeks and 24 weeks; Overall Survival (OS); OS rate at 12 months).
6. Part C: Safety (Nature, incidence and severity of TEAE (including DLT like events and AESI), of SAE, SUSARs graded according to CTCAE grading version 5.0).

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

OSE Immunotherapeutics

Sponsor organisation

OSE Immunotherapeutics

Address

22 Boulevard Benoni Goullin

City

Nantes

Postcode

44200

Country

France

Scientific contact point

Organisation

OSE Immunotherapeutics

Contact name

Lucie BEGERT

Public contact point

Organisation

OSE Immunotherapeutics

Contact name

Lucie BEGERT

Third parties 15

Locations

3 EU/EEA countries · 13 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 44 files

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

Application history

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