| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Patients with metastatic or unresectable, recurrent HNSCC |
|
| E.1.1.1 | Medical condition in easily understood language |
| Patients with metastatic or unresectable, recurrent HNSCC |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| 1. To evaluate Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) |
|
| E.2.2 | Secondary objectives of the trial |
1. To evaluate Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
2. To evaluate Duration of Response (DOR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
3. To evaluate Overall Survival (OS)
4. To assess the safety and tolerability of study treatment
|
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
| Merck will conduct Future Biomedical Research on DNA (Blood) specimens collected during this clinical trial. Such research is for biomarker testing to address emergent questions not described elsewhere in the protocol (as part of the main trial) and will only be conducted on specimens from appropriately consented subjects. The objective of collecting specimens for Future Biomedical Research is to explore and identify biomarkers that inform the scientific understanding diseases and/or their therapeutic treatments. The overarching goal is to use such information to develop safer, more effective drugs, and/or to ensure that subjects receive the correct dose of the correct drug at the correct time. |
|
| E.3 | Principal inclusion criteria |
1. Has histologically or cytologically confirmed diagnosis of metastatic or unresectable,recurrent HNSCC that is considered incurable by local therapies.
Has not had prior systemic therapy administered in the recurrent or metastatic setting. Systemic therapy which was completed more than 6 months prior to signing consent, if given as part of multimodal treatment for locally advanced disease, is allowed.
The eligible primary tumor must be located in oropharynx, oral cavity, hypopharynx, or larynx. Participants may not have a primary tumor site of nasopharynx (any histology).
2. Has tumor PD-L1 expression of CPS ≥1.
3. Has at least 1 measurable lesion which is amenable to injection. IT injection for cutaneous lesions may be performed via visual inspection. IT injection for subcutaneous lesions may be performed via ultrasound guidance or via palpation. This injectable lesion must be measurable and meet one of the following criteria:
A cutaneous or subcutaneous lesion ≥1 cm in longest diameter for solid tumors, or ≥1.5 cm in short axis for a nodal lesion in solid tumor subjects. The longest diameter for an injectable lesion must be ≤10 cm for both solid tumors and nodal lesions in solid tumor subjects.
Multiple coalescing, superficial lesions which in aggregate have a longest diameter of ≥1 cm and ≤10 cm.
4. Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
5. Demonstrates adequate organ function
6. Has results from testing of HPV status for oropharyngeal cancer defined as p16 IHC testing using CINtec® p16 Histology assay and a 70% cutoff point (please see the Procedures Manual for details). If HPV status was previously tested, then no additional testing is required.
7. Is male or female, from 18 years to unlimited years of age inclusive, at the time of signing the informed consent.
8. Male participants of reproductive potential must agree to use a highly effective method of contraception during sexual contact with females of childbearing potential starting with the first dose of study medication through 120 days after the last dose of study therapy.
9. Female participants of childbearing potential must be willing to use a highly effective method of birth control or be surgically sterile or abstain from heterosexual activity for the course of the study through 120 days after last dose of study medication . Participants of childbearing potential are those who have not been surgically sterilized or have not been free of menses for >1 year.
10. Female participants of childbearing potential must have a negative urine or serum pregnancy test at screening and again within 72 hours prior to receiving the first dose of study treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. The serum pregnancy test must be negative for the participant to be eligible.
11. Has voluntarily agreed to participate by giving written informed consent. The participant may also provide consent for Future Biomedical Research. However, the participant may participate in the main trial without participating in Future Biomedical Research.
12. HIV-infected participants must meet these additional criteria:
a) Have HIV-1 infection documented by using any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry (Day 1). HIV-1 infection is to be confirmed by using a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 p24 antigen, or plasma HIV-1 RNA VL.
b) Have well-controlled HIV on anti-retroviral therapy (ART), defined as:
1) must have a CD4+ T-cell count >350 cells/mm3 at time of screening;
2) must have achieved and maintained virologic suppression, defined as confirmed HIV RNA level below 50 copies/mL or below the LLOQ (lowest
limit of quantification) using the locally available assay at the time of screening and for at least 12 weeks prior to screening;
3) must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks prior to study entry (Day 1). |
|
| E.4 | Principal exclusion criteria |
1.Has disease that is suitable for local therapy administered with curative intent
2. Has progressive disease within 6 months of completion of curatively intended systemic treatment for locoregionally advanced HNSCC
3. Has had chemotherapy or biological cancer therapy in the recurrent or metastatic setting for the treatment of HNSCC
4. Has had radiation therapy within 2 weeks prior to randomization or subject has not fully recovered from adverse events due to a previously administered treatment
5. Is expected to require any other form of antineoplastic therapy while on study
6. Has a history of a second malignancy, unless potentially curative treatment has been completed, with no evidence of malignancy for at least 2 years
7. Has clinically active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain or meningeal metastases may participate and be eligible for treatment provided they are stable and asymptomatic, have no evidence of new or enlarging brain metastases, are evaluated within 4 weeks prior to first study intervention administration, and are off immunosuppressive doses of systemic steroids at least 2 weeks prior to enrolment
8. Has an active autoimmune disease that has required systemic treatment in the past 2 years except vitiligo or resolved childhood asthma/atopy. Replacement therapy, such as thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, is not considered a form of systemic treatment and is allowed. Use of nonsystemic steroids is permitted
9. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Corticosteroid use as premedication for allergic reactions is allowed
10. Has had an allogenic tissue/solid organ transplant
11. Has a history of vasculitis
12. Has a history of interstitial lung disease
13. Has an active infection requiring systemic therapy
14. Has a known history of active tuberculosis
15. Has a history of pneumonitis that required steroids or current pneumonitis
16. Has had a severe hypersensitivity reaction to treatment a monoclonal antibody/component of the study intervention
17. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject’s participation for the full duration of the study in the opinion of the treating investigator
18. Participants with known Hepatitis B or C infections or known to be positive for HBsAg/HBV DNA or Hepatitis C Antibody or RNA.
19. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or if the patient has previously participated in Merck MK-3475 clinical trials
20. HIV infected participants who have had an HIV-related opportunistic infection within 6 months
21. HIV infected participants with a history of Kaposi’s sarcoma and/or Multicentric Castleman’s Disease
22. Has known psychiatric or substance abuse disorders that would interfere with the participant’s ability to cooperate with the requirements of the study
23. Is pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study intervention
24. Has not fully recovered from any effects of major surgery without significant detectable infection. Surgeries that required general anesthesia must be completed at least 2 weeks before first study intervention administration. Surgery requiring regional/epidural anesthesia must be completed at least 72 hours before first study intervention administration and participants should be recovered
25. Has a tumor(s) in direct contact or encases a major blood vessel with or without ulceration and/or fungation onto the skin surface at the projected injection site in the head or neck.
26. Has a history of reirradiation for HNSCC at the projected injection site in the head and neck
27. Has received a live-virus vaccine within 30 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted
28. Drug-drug interactions have to be taken into consideration, and decisions whether a particular drug can be used as a concomitant medication in the study should be based on recommendations at the time of the study and depending on the MOA of the study drug. Patients on ART agents with a potentially significant overlapping toxicity profile should be excluded if the therapy cannot be switched to the regimen without overlapping toxicity.
29. Has been treated with a STING agonist
30. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy, or used an investigational device, any of which occurred within 4 weeks of the first dose of treatment.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| 1. Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| 1. Up to approximately 2 years |
|
| E.5.2 | Secondary end point(s) |
1. Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
2. Duration of Response (DOR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
3. Overall Survival (OS)
4. Number of participants experiencing an Adverse Event (AE)
5. Number of participants discontinuing study treatment due to an Adverse Event (AE) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Up to approximately 2 years
2. Up to approximately 2 years
3. Up to approximately 2 years
4. Up to approximately 2 years
5. Up to approximately 2 years |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 14 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Australia |
| Austria |
| Brazil |
| France |
| Israel |
| Korea, Republic of |
| Mexico |
| Norway |
| Spain |
| United Kingdom |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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