Phase II Study of efti plus pembrolizumab combination therapy for head and neck cancer (HNSCC).

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Immutep

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

30 Nov 2021 → 6 Nov 2025

Decision date (initial)

2024-08-13

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Immutep S.A.S

External identifiers

EU CT number

2024-510762-16-00

EudraCT number

2021-000055-39

ClinicalTrials.gov

NCT04811027

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety, Pharmacogenomic

To evaluate the objective response rate of efti in combination with pembrolizumab in Cohort A and to compare to pembrolizumab alone in Cohort A, overall and also as per stratification factors (e.g. CPS).
To evaluate the objective response rate of efti in combination with pembrolizumab in Cohort B.

Secondary objectives 3

1. To evaluate overall survival and further antitumor activity of efti when combined with pembrolizumab in Cohort A and to compare to pembrolizumab alone Cohort A, overall and also as per stratification factors (e.g. CPS). To evaluate the overall survival and further antitumor activity of efti when combined with pembrolizumab in Cohort B.
2. To evaluate the safety and tolerability of efti when combined with pembrolizumab compared to pembrolizumab alone.
3. To assess the immunogenic properties of efti when combined with pembrolizumab

Conditions and MedDRA coding

Metastatic head and neck squamous cell carcinoma (HNSCC)

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-002698-PIP02-22

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. Willing to give written informed consent and to comply with the protocol.
2. Histologically- or cytologically confirmed recurrent disease not amenable to curative treatment with local or systemic therapy, or metastatic (disseminated) HNSCC of the oral cavity, oropharynx, hypopharynx, or larynx that is considered incurable by local therapies and to be treated in the first line palliative setting and who are PD-X naïve.
3. Availability of tissue for PD-L1 biomarker analysis from a core or excisional biopsy (fine needle aspirate is not sufficient). A newly obtained biopsy (within 90 days prior to start of trial treatment) is preferred but an archival sample is acceptable.
4. Availability of PD-L1 biomarker result by using the FDA approved Dako standardized diagnostic test (PD-L1 IHC 22C3 pharmDx)
5. Availability of tissue for testing of human papillomavirus (HPV) status for oropharyngeal carcinoma (p16 expression testing). Note: If HPV status was previously tested using this method and result isavailable, no additional testing in central laboratory is required for this trial.
6. Female or male ≥18 years of age on the day of signing the informed consent.
7. All female subjects of childbearing potential must have a negative highly sensitive pregnancy test at screening (within 72 hours prior to cycle 1 day 1); all subjects of reproductive potential must agree to use highly effective method for contraception from trial entry until at least 4 months after the last administration of any trial treatment
8. A woman must either be, a) not of childbearing potential: postmenopausal (≥ 60 years of age, or < 60 years of age and amenorrhoeic for 12 months in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression with follicle-stimulating hormone (FSH) above 40 U/L and estradiol below 30ng/L, or if taking tamoxifen or toremifene, and age < 60 years, then FSH and estradiol in the postmenopausal range), permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy), or otherwise incapable of pregnancy b) of childbearing potential and practicing a highly effective method of birth control consistent with local regulations regarding the use of birth control methods for subjects participating in clinical studies: e.g., established use of oral, injected or implanted hormonal methods of contraception; placement of an intrauterine device or intrauterine system; male partner sterilization (the vasectomized partner should be the sole partner for that subject).
9. ECOG performance status 0-1.
10. Evidence of measurable disease as defined by Response Evaluation Criteria in Solid Tumors version 1.1. Lesions situated in a previously irradiated area is considered measurable if progression has been demonstrated in such lesions.
11. Subjects who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization. Note: Subjects should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of trial intervention.Hepatitis B screening test are not required unless: a) known history of HBV infection. b) mandated by local health authority.
12. Subjects with history of HCV infection are eligible if HCV viral load is undetectable at screening.
13. HIV infected subjects must be on anti-retroviral therapy and have a well-controlled HIV infection/disease defined as: a) Subjects on ART must have a CD4+ T-cell count >350 cells/mm3 at time of screening b) Subjects on ART must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 copies/mL or the lower limit of qualification (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks prior to screening c) Subjects on ART must have been on stable regimen, without changes in drugs or dose modification, for at least 4 weeks prior to cycle 1 day 1 Note: no HIV testing is required unless mandated by local health authority.
14. Laboratory criteria: a) Absolute neutrophil count > 1.5 x 10^9/L b) Platelet count ≥ 100 x 10^9/L c) Hemoglobin ≥ 9 g/dL or 5.58 mmol/L d) Serum creatinine ≤ 1.5 × ULN, or if > 1.5 ULN with a clearance of ≥ 50 mL/min acc. to Gault-Cockcroft formula e) Total bilirubin ≤ 1.5 x ULN or direct bilirubin ≤ ULN for subjects with total bilirubin > 1.5 x ULN Note: subjects with known Gilbert's syndrome can be enrolled. f) AST (=SGOT) and ALT (=SGPT) ≤ 2.5 x ULN or ≤ 5 x ULN if liver metastases are present. g) International normalized ratio (INR) or prothrombin time (PT) ≤1.5 ×ULN unless subject is receiving anticoagulant therapy as long as PT or activated partial thromboplastin time (aPTT) is within therapeutic range of intended use of anticoagulants

Exclusion criteria 25

1. Disease is suitable for local therapy administered with curative intent
2. Previously treated with ≥ 1 systemic regimen for recurrent and/or metastatic disease (with the exception of systemic therapy completed >6 months prior if given as part of multimodal treatment for locally or locoregionally advanced disease)
3. Histologically or cytologically confirmed head and neck carcinoma of any other primary anatomic location in the head and neck not specified in the inclusion criteria including subjects with HNSCC of unknown primary, squamous cell carcinoma originating from skin, or nonsquamous histologies (e.g. nasopharynx, salivary gland or mucosal melanoma)
4. Has progressive disease (PD) within 6 months of completion of curatively intended systemic treatment for locally or locoregionally advanced HNSCC, or requires chemotherapy based therapeutic regimen due to e.g., rapidly progressing disease or need of aggressive symptom control.
5. Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic Tlymphocyte-associated antigen-4 antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co- stimulation or checkpoint pathways)
6. No PD-L1 expression result available by cycle 1 day 1.
7. Prior anti-LAG-3 therapy
8. Prior high-dose chemotherapy requiring hematopoietic stem cell rescue.
9. Prior targeted small molecule therapy, or radiation therapy within 2 weeks prior to cycle 1 day 1.
10. Has received prior chemotherapy, anti-cancer monoclonal antibody, major surgery, another systemic cancer therapy or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to cycle 1 day 1.
11. Known active central nervous system metastasis and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are radiologically stable: i.e. without evidence of progression documented by repeat imaging performed after therapy completed for CNS metastasis and with at least 4 weeks difference, clinically stable and without requirement for steroid treatment for at least 14 days prior to cycle 1 day 1.
12. Pregnant, breastfeeding or expecting to conceive or father children within the projected duration of the trial starting with screening visit. A woman of child-bearing potential who has a positive serum pregnancy test (within 72 hours) prior to cycle 1 day 1.
13. Serious intercurrent infection within 4 weeks prior to cycle 1 day 1 or active acute or chronic infection.
14. Evidence of severe or uncontrolled cardiac disease within 6 months prior to first dose of trial treatment including: myocardial infarction, severe/unstable angina, ongoing cardiac dysrhythmias of NCI CTCAE version 5.0 Grade ≥ 2, atrial fibrillation > grade 2 not controlled by a pacemaker, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (NYHA III-IV), cerebrovascular accident including transient ischemic attack, or symptomatic pulmonary embolism.
15. Has interstitial lung disease or history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
16. Has active 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 ofsystemic treatment and is allowed.
17. HIV-infected subjects with a history of Kaposi sarcoma and/or Multicentric Castleman Disease.
18. Has a life-threatening illness unrelated to cancer.
19. Has had an allogenic tissue/solid organ transplant.
20. Has previous malignancies within the last three years other than described in inclusion criterion 2,except curatively treated basal or squamous cell carcinoma of the skin, superficial bladder cancer, ductal carcinoma in situ of the breast, or in situ carcinoma of the cervix.
21. Receives continuous systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 7 days prior to cycle 1 day 1. Inhaled or topical steroids and physiological replacement doses of up to 10 mg daily prednisone equivalents are permitted in the absence of active auto-immune disease.
22. Has a hypersensitivity to efti and/or pembrolizumab and/or any of its excipients.
23. Live vaccine within 30 days of planned cycle 1 day 1.
24. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating Investigator.
25. Has known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the trial.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Objective response rate (ORR) according to RECIST1.1

Secondary endpoints 8

1. Overall survival (OS)
2. Objective response rate (ORR) according to iRECIST
3. Time to and duration of responses according to iRECIST and RECIST 1.1
4. Disease control rate according to iRECIST and RECIST 1.1
5. Progression free survival (PFS) according to iRECIST and RECIST 1.1
6. Occurrence of anti-efti-specific antibodies
7. Safety profile in terms of frequency, severity and duration of Adverse events (AEs) and serious adverse events (SAEs) and events of clinical interest (ECI) and abnormalities in vital signs, physical examination, 12- lead ECG and safety laboratory assessments
8. Quality of Life using EORTC QLQ-H&N43 and EORTC QLQ-30

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Immutep

Sponsor organisation

Immutep

Address

Batiment 7 Le Pythagore Route De L Orme Route Departementale, 128 Parc Des Algorithmes 128 Parc Des Algorithmes

City

St Aubin

Postcode

91190

Country

France

Scientific contact point

Organisation

Immutep

Contact name

Clinical Trials Enquires

Public contact point

Organisation

Immutep

Contact name

Clinical Trials Enquires

Third parties 7

Locations

5 EU/EEA countries · 19 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 35 files

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

Application history

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