A Randomized, Double-Blind, Multicenter, Phase 2 Study of Retifanlimab in Combination With INCAGN02385 (Anti–LAG-3) and INCAGN02390 (Anti–TIM-3) as First-Line Treatment in Participants With PD-L1–Positive (CPS ≥ 1) Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Incyte Biosciences International S.a.r.l.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

18 Oct 2022 → 27 May 2026

Decision date (initial)

2024-10-25

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Incyte Biosciences International Sarl

External identifiers

EU CT number

2023-504270-38-00

EudraCT number

2021-005775-39

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To determine the efficacy of the combinations of retifanlimab + INCAGN02385 (TG2) and retifanlimab + INCAGN02385 + INCAGN02390 (TG3) compared with retifanlimab alone (TG1) in the overall study population.

Secondary objectives 3

1. To assess disease response per RECIST v1.1 in TG2 and TG3 compared with TG1.
2. To determine the OS of TG2 and TG3 compared with TG1.
3. To determine the safety of TG2 and TG3 compared with TG1.

Conditions and MedDRA coding

In participants with PD-L1–positive and systemic therapy–naive R/M SCCHN.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Ability to comprehend and willingness to sign a written ICF for the study.
2. Age 18 years or older (or as applicable per local country requirements), inclusive at the time of signing the ICF.
3. Histologically or cytologically confirmed R/M SCCHN that is not amenable to therapy with curative intent (surgery and/or radiation therapy with or without chemotherapy). Participants who refuse potentially curative salvage surgery for recurrent disease are ineligible.
4. PD-L1 positive tumor status defined by CPS ≥ 1 per central laboratory determination.
5. For participants with primary oropharyngeal tumors, documentation of HPV p16 status (positive or negative) based on local institutional standard is required. HPV p16 status is not required for other eligible SCCHN primary tumor sites.
6. Participant must have at least 1 measurable tumor lesion per RECIST v1.1.
7. Availability of archival tissue for biomarker analysis from a core or excisional biopsy or willingness to undergo a fresh biopsy.
8. ECOG performance status of 0 or 1.
9. Willingness to avoid pregnancy or fathering children based on the criteria

Exclusion criteria 27

1. Progressive or recurrent disease within 6 months of the last dose of systemic treatment for locally advanced SCCHN.
2. Prior PD-(L)1, LAG-3, or TIM-3 directed therapy, or any other checkpoint inhibitor therapy, for SCCHN (in any disease setting) or any other malignancy.
3. Treatment with anticancer therapies or participation in another interventional clinical study within 21 days before the first administration of study treatment (this includes curative radiation to the thorax or systemic anticancer therapies).
4. Presence of tumors that invade major blood vessels, as shown unequivocally by imaging, and with active bleeding.
5. Less than 3-month life expectancy (based on investigator judgment).
6. Participant has not recovered to ≤ Grade 1 or baseline from residual toxicities of prior therapy (with exceptions for anemia not requiring transfusion support, fatigue, or any grade of alopecia).
7. Participant has not recovered adequately from toxicities and/or complications from surgical intervention before starting study treatment.
8. Palliative radiation therapy administered within 1 week before the first dose of study treatment or radiation therapy in the thoracic region that is > 30 Gy within 6 months before the first dose of study treatment.
9. Known active CNS metastases and/or carcinomatous meningitis. Participants will be excluded if it has been < 4 weeks since radiation therapy was delivered to the CNS.
10. Participants with laboratory values at screening defined in Table 7.
11. Has known active HBV or HCV infection, or risk of reactivation of HBV or HCV, defined as follows (testing must be performed to determine eligibility): a. Active HBV infection is defined by positive HBsAg and positive total anti-HBc results. Note: If HBsAg is negative AND HBcAb and/or HBsAb is positive, HBV-DNA will be evaluated; when HBV-DNA is negative, the participant can then be enrolled with close monitoring of HBV activities. b. Active HCV is defined as a positive HCV antibody result and quantitative HCV-RNA results greater than the lower limits of detection of the assay. Note: Participants positive for HCV antibody will be eligible if they are negative for HCV-RNA. Participants who have had definitive treatment for HCV are permitted if HCV RNA is undetectable.
12. Participants who are known to be HIV-positive, unless all of the following criteria are met: a. CD4+ count ≥ 300/μL. b. Undetectable viral load. c. Receiving antiretroviral therapy that is not a potential risk for a drug-drug interaction with the assigned study drug.
13. Any known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 3 years of the first dose of study treatment with the exception of cured basal cell or squamous cell carcinoma of the skin, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy, or cancers from which the participant has completed treatment > 2 years before randomization in this study and has been disease-free since completion of treatment with curative intent.
14. Has active autoimmune disease requiring systemic immunosuppression with corticosteroids (> 10 mg/day of prednisone or equivalent) or immunosuppressive drugs within 2 years before the first dose of study treatment.
15. Is on chronic systemic steroids (> 10 mg/day of prednisone or equivalent).
16. Active infections (besides those described in Exclusion Criteria 11 and 12) requiring systemic antibiotics or antifungal or antiviral treatment (within 14 days before first dose of study treatment).
17. Evidence of interstitial lung disease or history of interstitial lung disease, or active, noninfectious pneumonitis.
18. History of organ transplant, including allogeneic stem cell transplantation.
19. Receiving probiotics as of the first dose of study treatment.
20. History or presence of an abnormal ECG that, in the investigator's opinion, is clinically meaningful. Screening QTc interval > 460 milliseconds is excluded (corrected by Fridericia or Bazett formula). In the event that a single QTc is > 460 milliseconds, the participant may enroll if the average QTc for the 3 ECGs is ≤ 460 milliseconds
21. Has had a significant cardiac event within 6 months before the first dose of study treatment, including New York Heart Association Class III/IV, acute myocardial infarction (including severe/unstable angina), cardiomyopathy, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, critical conduction delay, cerebrovascular accident or transient ischemic attack, or pulmonary embolism.
22. Has received a live vaccine within 30 days of planned start of study treatment.
23. Known hypersensitivity to another monoclonal antibody that cannot be controlled with standard measures (eg, antihistamines and corticosteroids).
24. Known allergy or hypersensitivity to any component of either retifanlimab, INCAGN02385, or INCAGN02390 study drug formulation (including excipients and additives).
25. Women who are pregnant or breastfeeding.
26. Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study treatment and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.
27. The following participants are excluded in France: vulnerable populations according to article L.1121-6 of the French Public Health Code and adults under legal protection, or who are unable to express their consent per article L.1121-8 of the French Public Health Code.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. PFS, defined as the interval between the date of randomization and the earliest date of disease progression, based on investigator assessment per RECIST v1.1, or death due to any cause.

Secondary endpoints 3

1. • Objective response, defined as having a CR or PR, determined based on investigator assessment per RECIST v1.1. • DOR, defined as the time from earliest date of disease response (CR or PR) until earliest date of disease progression, based on investigator assessment per RECIST v1.1, or death from any cause if occurring sooner than progression. • Disease control, defined as having CR, PR, or SD (≥ 6 months) as best response, based on investigator assessment per RECIST v1.1.
2. OS, defined as the interval between the date of randomization until death due to any cause.
3. • AEs, assessed in body systems with symptoms, through physical examinations, changes in vital signs and ECGs, and through clinical laboratory blood sample evaluations. • Impact on-study treatment, assessed by treatment interruptions, dose delays, and withdrawal of study treatment due to AEs.

Investigational products

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

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Incyte Biosciences International S.a.r.l.

Sponsor organisation

Incyte Biosciences International S.a.r.l.

Address

Rue Docteur-Yersin 12

City

Morges

Postcode

1110

Country

Switzerland

Scientific contact point

Organisation

Incyte Biosciences International S.a.r.l.

Contact name

Clinical Trial Information

Public contact point

Organisation

Incyte Biosciences International S.a.r.l.

Contact name

Clinical Trial Information

Third parties 3

Locations

5 EU/EEA countries · 27 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 33 files

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

Application history

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