Induction and maintenance treatment with PARP inhibitor and immunotherapy in HPV-negative Head and Neck Squamous Cell Carcinoma (HNSCC). PRIME H&N study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione GONO Plus

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

8 Feb 2021 → ongoing

Decision date (initial)

2024-11-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

GLAXOSMITHKLINE LLC

External identifiers

EU CT number

2024-516798-54-00

EudraCT number

2019-004875-38

ClinicalTrials.gov

NCT04681469

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate the activity of the study treatment combination in HNSCC

Secondary objectives 1

1. • To evaluate the safety of the study treatment combination • to evaluate the disease-free survival (DFS) of the whole treatment • to evaluate the predictive role of baseline genomic expression, immune infiltrate, PD-L1 evaluation (by CPS) and radiomic characteristics with regard to response to induction therapy and DFS. • to evaluate the changes in gene expression and immune infiltrates in tumor samples and in salivary immune related biomarkers and to correlate them with pathological response after induction therapy.

Conditions and MedDRA coding

HPV-negative Head and Neck Squamous Cell Carcinoma (HNSCC)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 3. Primary histologically proven squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx amenable to surgery with curative intent. p16 negative status will be requested only for oropharyngeal cancer and it will be assessed as surrogate marker for HPV infection. p16 status will be assessed using the CINtec p16 Histology assay (Ventana Medical Systems, Tucson, AZ, USA) with strong and diffuse nuclear and cytoplasmic staining in at least 70% of cells used as the cutpoint for positivity. 4. Clinical stage III-IV(M0) according to the VIII edition of AJCC staging system; recurrent/metastatic HNSCC, or previously treated HNSCC with local or systemic therapies, are not eligible for this study. 5. Performance status ECOG 0-1; 8. Absence of a second malignancy (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, oesophageal, colon, endometrial, cervical/dysplasia, melanoma, or breast) unless a complete remission was achieved at least 2 years prior to study entry AND no additional therapy is required during the study period; 9. Patient has adequate organ and marrow function (absolute neutrophil count ≥ 1500, hemoglobin ≥ 9.0 gram/deciliter (g/dL), platelet count ≥ 100,000, total bilirubin ≤1.5 times institution's upper limit of normal, AST/SGOT and ALT/SPGT ≤ 2.5 times institutional upper limit of normal, albumin ≥ 2.0 g/dL, serum creatinine ≤ 1.5 times institutional upper limit of normal or creatinine clearance ≥ 60 milliliters per minute (mL/min) according to Cockroft-Gault formula, or local institutional standard method); 10. Patient must be able to swallow study drug; 11. Participant must agree to not donate blood during the study or for 90 days after the last dose of study treatment; 12. Female participant has a negative serum pregnancy test within 72 hours prior to taking study treatment if of childbearing potential and agrees to use an adequate method of contraception from screening through 180 days after the last dose of study treatment, or is of nonchildbearing potential. Nonchildbearing potential is defined as follows (by other than medical reasons): • ≥45 years of age and has not had menses for >1 year • Patients who have been amenorrhoeic for <2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation • Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure, otherwise the patient must be willing to use an adequate barrier method throughout the study, starting with the screening visit through 180 days after the last dose of study treatment. See Section 3.3 for a list of acceptable birth control methods. Information must be captured appropriately within the site’s source documents. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient. 13. Participant must agree to not breastfeed during the study or for 120 days after the last dose of study treatment; 14. Male participant agrees to use an adequate method of contraception (Section 3.3 for a list of acceptable birth control methods) starting with the first dose of study treatment through 180 days after the last dose of study treatment. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient;

Exclusion criteria 1

1. 1. Patient has recurrent/metastatic disease; 2. Patient with locally advanced disease not amenable of surgery with curative intent; 3. Patient has received prior local or systemic treatment for HNSCC; 4. Patient with p16/HPV positive HNSCC; 5. Patient with sinonasal, nasal cavity or nasopharyngeal cancer; 6. Patient with SCC on neck disease with unknown primary tumor site; 10. Participant has had radiation therapy encompassing >20% of the bone marrow within 2 weeks; or any radiation therapy within 1 week prior to Day 1 of protocol therapy; 12. Participant must not have received a transfusion (platelets or red blood cells) ≤ 4 weeks prior to initiating protocol therapy; 13. Participant must not have received colony-stimulating factors (eg, granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor, or recombinant erythropoietin) within 4 weeks prior initiating protocol therapy; 14. Participant has had any known Grade 3 or 4 anemia, neutropenia or thrombocytopenia due to prior chemotherapy that persisted > 4 weeks and was related to the most recent treatment; 15. Participant must not have any known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML); 17. Participant must not have known, symptomatic brain or leptomeningeal metastases; 18. Patient experienced ≥ Grade 3 immune-related adverse event with prior immunotherapy, with the exception of non-clinically significant lab abnormalities; 19. Participant has a diagnosis of immunodeficiency or has received systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to initiating protocol therapy; 21. Subjects with previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, oesophageal, colon, endometrial, cervical/dysplasia, melanoma, or breast) unless a complete remission was achieved at least 2 years prior to study entry AND no additional therapy is required during the study period; 22. Subjects with an active, known or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll; 23. Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrollment. Inhaled or topical steroids, and adrenal replacement steroid > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease; 24. Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity; 26. Known active Hepatitis B infection (defined as presence of HBsAg and/or HBV DNA), active hepatitis C infection (defined as presence of Hep C RNA) and/or known Human Immunodeficiency Virus (HIV). Patients with HIV who have a normal CD4 count (≥ 200) and an undetectable viral load are not excluded; 27. Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 72 hours before treatment start. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial and 180 days after the last dose of study treatment;

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Efficacy: Rate of Major Pathological Response (MPR, i.e. less than 10% viable tumor cells identified on routine hematoxylin and eosin staining in pathological surgical specimen) in patients with locally advanced HNSCC treated with Niraparib + Dostarlimab (TSR-042) in the WoO setting.

Secondary endpoints 4

1. Safety: Safety stopping rule: the first 6 patients will be evaluated for surgical toxicities graded according to Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 and documented over the 4 weeks period following surgery in order to determine if preoperative study protocol is safe.
2. Once the safety is established total planned enrolment will be completed. Surgical safety in the whole population will be evaluated up to 4 weeks after surgery considering the following: a) postoperative bleeding requiring surgical revision b) delayed wound healing or wound dehiscence c) wound infection d) fistula e) need for secondary surgical interventions (not considered part of institutional standard of care) f) skin loss/flap necrosis including partial or total flap as applicable.
3. • Two-year DFS of the patients enrolled in the trial, defined as the time from treatment assignment to cancer recurrence, second cancer or death from any cause. • radiological response after 6 weeks of treatment evaluated at MRI prior to surgery by: a) RECIST v1.1 using conventional MRI imaging b) Diffusion Weighted Imaging Magnetic Resonance Imaging (DWI MRI)
4. • Safety of the whole treatment and safety of each phase (induction and maintenance) as evaluated in a separate way • correlation between radiological and pathological response; • evaluation of predictive role of baseline genomic expression, salivary markers and radiomic characteristics on response to induction therapy; • change in gene expression in tumor samples after induction therapy;

Investigational products

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

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione GONO Plus

Sponsor organisation

Fondazione GONO Plus

Address

Interno 11, Via Cesarea 8 Via Cesarea 8

City

Genoa

Postcode

16121

Country

Italy

Scientific contact point

Organisation

Fondazione GONO Plus

Contact name

Paolo Bossi

Public contact point

Organisation

Fondazione GONO Plus

Contact name

Paolo Bossi

Third parties 1

Locations

1 EU/EEA country · 8 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 9 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