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

Phase 1

• Conditions: Metastatic head and neck squamous cell carcinoma (HNSCC); MedDRA version: 21.1Level: PTClassification code 10071540Term: Head and neck cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2021-000055-39-ES
• Lead Sponsor: Immutep S.A.S.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-07-13
• Last Update Posted: 26 October 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 154

Inclusion Criteria

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 is available, 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 30
ng/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 are 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)

Exclusion Criteria

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 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 locoregionally advanced HNSCC
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 of systemic treatment and is allowed.
17. HIV-infected subjects with a history of Kaposi sarcoma and/or Multicentric Castleman
Disease.
18. Has a life-threate

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified