A study of PRS-344/S095012 (PD-L1x4-1BB bispecific antibody) in patients with solid tumors

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Institut De Recherches Internationales Servier IRIS

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

2 Sep 2021 → 2 Apr 2025

Decision date (initial)

2024-06-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

ADIR France · Laboratorios Servier, S. L

External identifiers

EU CT number

2023-510046-25-00

EudraCT number

2019-003456-36

ClinicalTrials.gov

NCT05159388

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Dose response, Pharmacodynamic, Pharmacokinetic

Phase 1:
- To evaluate the safety and tolerability profile of single-agent PRS-344/S095012
- To determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) and the recommended phase 2 dose (RP2D) of PRS-344/S095012

Phase 2: To evaluate the potential anti-tumor activity and efficacy of PRS-344/S095012, as per central assessment according to RECIST v1.1 criteria based on appropriate clinical standards for the specified tumor type

Secondary objectives 7

1. Phase 1: To characterize the PK of PRS-344/S095012
2. Phase 1: To evaluate the immunogenicity of PRS-344/S095012
3. Phase 1: To assess the preliminary anti-tumor activity of PRS-344/S095012 as per the investigator, according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
4. Phase 2: To further describe the efficacy
5. Phase 2: To further characterize the safety and tolerability of PRS-344/S095012
6. Phase 2: To further characterize the PK profile of PRS- 344/S095012
7. Phase 2: To further characterize immunogenicity of PRS-344/S095012

Conditions and MedDRA coding

Soild Tumors

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 17

1. Age ≥18 years on the day the consent is signed.
2. Patient must have a life expectancy of at least 3 months.
3. Patient should have a documented disease progression on prior therapy before entry into this study
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
5. Royal Marsden Prognosis score of 0 to 1 (score based on lactate dehydrogenase (LDH) value, albumin value and number of sites of metastasis).
6. Adequate organ function as assessed by laboratory tests within 7 days prior to pretreatment with obinutuzumab: -Lymphocyte count ≥ 800/μ -Gamma-globulin level > 6g/L (by serum protein electrophoresis) or IgG level > 4g/L (by measurement of quantitative immunoglobulins)
7. A female patient must use a highly effective method of birth control during study treatment and until, for 120 days after the last dose of the study treatment. PRS-344/S095012, or 18 months after the last obinutuzumab infusion, whichever comes the latest.
8. A male patient with childbearing potential partners must use a condom during the study and for at least 4 months after the last dose of the study treatment, or 6 months after the last Obinutuzumab infusion, whichever comes the latest. Sperm donation will not be allowed during the study and for 4 months after the last dose of study treatment, or 6 months after the last obinutuzumab infusion, whichever comes the latest.
9. Test should be negative for cytomegalovirus (CMV), Epstein-Barr virus (EBV), Hepatitis B virus (HBV), and Hepatitis C virus (HCV) infection, according to local standards: - Negative CMV DNA testing in serum or plasma by a sensitive quantitative molecular method. - Absence of immunoglobulin (Ig)M antibodies against EBV-VCA (Viral Capside Antigen) - Negative serologic testing for hepatitis B surface antigen (HbsAg) or a negative result by a sensitive quantitative molecular method for HBVDNA in serum or plasma -Negative HCV RNA testing in serum or plasma by a sensitive quantitative molecular method.
10. Negative test results for human T-lymphotropic virus 1 (HTLV 1). HTLV testing is only required for participants from countries in which HTLV 1 infection is endemic (Japan, countries in the Caribbean basin,South America, Central America, sub-Saharan Africa, and Melanesia).
11. Dose Escalation: Patients with a histological diagnosis of an unresectable, locally advanced or metastatic solid tumor for which standard treatment options are not available, no longer effective, or not tolerated.
12. Dose Escalation: Patients must have measurable disease per RECIST 1.1 as assessed by the local site investigator/imaging. Lesions situated in a previously irradiated area are considered measurable only if progression has been demonstrated in such lesions.
13. Dose Escalation:Patients with no available archived material must have one or more tumor lesions amenable to biopsy
14. Dose Expansion: Patients with histologically diagnosed Arm 1 and 2: recurrent, persistent, and/or metastatic cervical cancer. Acceptable histologies are squamous carcinoma, adenocarcinoma, and adenosquamous carcinoma. Arm 3: locally advanced or metastatic cutaneous squamous cell carcinoma.
15. Dose Expansion: Patients must have received : Arm 1 (cervical , CPI-naïve): at least 1 prior line of platinum-based combination therapy. Patients must not have received any prior treatment with an immune checkpoint inhibitor (anti-PD-1, PD-L1 or anti-CTLA-4 [cytotoxic T lymphocyte-associated protein 4]) and do not have access to an approved immune checkpoint inhibitor. Surgery, radiation therapy, and additional chemotherapy must not be considered appropriate alternative treatment options for these patients. Arm 2 (cervical cancer, CPI-relapsed/refractory): at least 1 prior line of systemic therapy with an immune checkpoint inhibitor as monotherapy or in combination with chemotherapy and/or any other systemic therapies. Surgery, radiation therapy, and additional chemotherapy must not be considered appropriate lternative treatment options for these patients. Arm 3 (CSCC, CPI-relapsed/refractory): at least 1 prior line of systemic therapy with an immune checkpoint inhibitor as monotherapy or in combination with chemotherapy and/or any other systemic therapies. Surgery, radiation therapy, and additional chemotherapy must not be considered appropriate alternative treatment options for these patients.
16. Dose Expansion: Biopsy requirements Arms 1 and 2 (cervical cancer): fresh baseline biopsies are mandatory, on-treatment biopsies are optional. Arm 3 (skin cancer): fresh baseline biopsies are mandatory, on-treatment biopsies are mandatory unless medically contra-indicated.
17. Dose Expansion: Patients must have at least one measurable target lesion as per RECIST 1.1 and/or World Health Organization (WHO) criteria for only externally visible skin tumors confirmed by central review. Lesions situated in a previously irradiated area are considered measurable only if progression has been demonstrated in such lesions

Exclusion criteria 9

1. Patients with previously treated brain metastases may participate provided they are radiologically stable, clinically asymptomatic and are off immunosuppressive therapies for at least 4 weeks. Low dose of steroid (≤ 10 mg/day prednisone or equivalent) is allowed
2. Patients who have received prior: a. Chemotherapy, small molecule inhibitors, monoclonal antibodies, antibody-drug conjugates, and/or other similar investigational agent: at least 3 weeks or 5 half-lives prior to first IMP administration, whichever is shorter. b. Radioimmunoconjugates or other similar experimental therapies at least 6 weeks or 5 half-lives prior to first IMP administration, whichever is shorter.
3. Patients who have received a 4-1BB agonist in the past.
4. Patients who had a major surgery within 4 weeks prior to first administration of IMP.
5. Patients who have received either systemic corticosteroids (> 10 mg per day or equivalent) or other immunosuppressive medications during the 2 months prior to the first dose of the study drug. Higher single doses of corticosteroids given as premedication against infusion-related reactions are allowed. Treatment with local steroids (inhaled, intranasal, injected are allowed.
6. Patients with an active infection with a viral, bacterial, or fungal pathogen requiring systemic treatment within seven days before first IMP administration.
7. Patients with a history of an opportunistic infection within a year prior to first IMP administration
8. History of progressive multifocal leukoencephalopathy.
9. Active tuberculosis requiring treatment within 3 years prior to the start of treatment or a suspicion of latent tuberculosis by the investigator.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 6

1. Phase 1: Incidence of DLTs
2. Phase 1: Incidence and severity of adverse events (AEs)
3. Phase 1: Discontinuation of study treatment due to an AE
4. Phase 1: Laboratory, electrocardiogram (ECG) and vital sign measurements
5. Phase 2: Arms 1 and 2: OR as per central assessment according to RECIST v1.1 criteriaper central assessment
6. Phase 2: Arm 3: OR as per central assessment and composite response criteria (digital medical photography and/or imaging as per RECIST v1.1)

Secondary endpoints 10

1. Phase 1: Serum PK parameters of PRS-344/S095012
2. Phase 1: Detection of antidrug antibodies (ADA) against PRS-344/S095012 and their titration when applicable
3. Phase 1: Objective Response (OR): Defined as Complete Response (CR) plus Partial Response (PR)
4. Phase 1: Duration of Response (DoR): defined as the time from first demonstration of response to progression or death, whichever occurs first
5. Phase 1: Progression-free Survival (PFS): Defined as the time from the first dose of treatment to first documented disease progression or death due to any cause, whichever occurs first
6. Phase 1: Overall Survival (OS): Defined as the time from first dose of study drug to death due to any cause
7. Phase 2: All arms: OR as per investigator assessment, Disease Control (DC), DoR, PFS, OS, Time to Response (TTR)
8. Phase 2: AEs, serious adverse events (SAEs), Laboratory, ECG, vital signs
9. Phase 2: Serum concentrations of PRS-344/S095012
10. Phase 2: Detection of ADA against PRS-344/S095012 and their titration when applicable

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Institut De Recherches Internationales Servier IRIS

Sponsor organisation

Institut De Recherches Internationales Servier IRIS

Address

22 Route 128

City

Gif Sur Yvette

Postcode

91190

Country

France

Scientific contact point

Organisation

Institut De Recherches Internationales Servier IRIS

Contact name

Clinical Studies Department

Public contact point

Organisation

Institut De Recherches Internationales Servier IRIS

Contact name

Clinical Studies Department

Third parties 8

Locations

3 EU/EEA countries · 16 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 2 · Art. 38 CTR

Results and documents

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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 21 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