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Submitted by: Trishia Torero 2020-10-09 07:59:34 Last Updated by: Trishia Torero 2021-04-12 15:47:12


A Phase 3 Randomized, Double-blind, Multicenter, Global Study of Monalizumab or Placebo in Combination With Cetuximab in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck Previously Treated With an Immune Checkpoint Inhibitor (INTERLINK-1)

PHRR201012-003024

D7310C00001

2020-CT0556

A Phase 3 Randomized, Double-blind, Multicenter, Global Study of Monalizumab or Placebo in Combination With Cetuximab in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck Previously Treated With an Immune Checkpoint Inhibitor

Study D7310C00001 is a Phase 3, randomized, double-blind, multicenter, global study assessing efficacy and safety of monalizumab and cetuximab compared to placebo and cetuximab in participants with R/M SCCHN previously treated with platinum-based chemotherapy and an ICI, regardless of the sequence of these therapies. 

Regime Classification Priority
2017 - 2022 Global competitiveness and innovation in health Drug discovery and development
Start Date Duration in Months Target Completion Date Actual Completion Date
2021-01-23 27 2023-04-23 0000-00-00

Ongoing

Institution Classification Region LTO #
AstraZeneca Pharmaceuticals (Philippines) Inc. Private Business NCR LTO-3000002234602
Institution Region
AstraZeneca AB Sweden
Name E-Mail Institution and Institution Address
Ryan Jay Natividad ryanjay.natividad@astrazeneca.com 16th Floor, Inoza Tower, 40th Street, Bonifacio Global City, Taguig, 1634, Philippines
Name E-Mail Institution and Institution Address
Ryan Jay Natividad ryanjay.natividad@astrazeneca.com 16th Floor, Inoza Tower, 40th Street, Bonifacio Global City, Taguig, 1634, Philippines
Name Expertise Affiliation
Jerry Tan Chun Bing, MD Oncology Cebu Doctors' University Hospital
John P. Querol, MD Oncology Veterans Memorial Medical Center
Project Location Institutional Ethics Review Board
Cebu Doctors' University Hospital Cebu Doctors' University Hospital - Institutional Ethics Review Committee
Veterans Memorial Medical Center Veterans Memorial Medical Center Ethics Review Committee

Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck Previously Treated With an Immune Checkpoint Inhibitor

• Population: The FAS which will include all randomized participants
• Endpoint: OS, which is defined as time from randomization until the date of death due to any cause
• Intercurrent events: If a participant is lost to follow-up or withdraws consent, OS will be censored based on the last recorded date on which the participant was known to be alive
• Summary measure: p-value of treatment comparison using a stratified log rank test and hazard ratio of Arm A relative to Arm B with its confidence interval using a stratified Cox Proportional Hazards model

  • PFS is defined as time from randomization until disease progression, per RECIST 1.1 as assessed by the investigator at local site or death due to any cause, whichever occurs first.
  • ORR is defined as the proportion of participants with measurable disease who have a confirmed CR or PR, as determined by the investigator at local site per RECIST 1.1.
  • DoR is defined as the time from the date of first documented response until date of documented disease progression or death in the absence of disease progression.

Symptoms, functioning, and global health
status/QoL scale/item scores of the EORTC QLQC30
& EORTC QLQ-H&N35
Change from baseline scores across visits
Time to clinically meaningful deterioration in scores

  • Concentration of monalizumab in blood and PK parameters (such as Cmax, Ctrough, as data allow; sparse sampling)
  • Presence of ADAs for monalizumab (confirmatory results: positive or negative, titers)
  • HLA-E and NKp46+ expression in pre-treatment and post-treatment tumor biopsies
  • AEs, vital signs, clinical laboratory results, ECGs

 

 

Pending

  • Argentina
  • Australia
  • Austria
  • Belgium
  • Brazil
  • Bulgaria
  • Canada
  • France
  • Germany
  • Greece
  • Italy
  • Japan
  • Netherlands
  • Peru
  • Philippines
  • Poland
  • Portugal
  • Romania
  • Russia
  • South Korea
  • Spain
  • Switzerland
  • Taiwan
  • United Kingdom
  • United States

Clinical Trial

D7310C00001

20200529150010

2020-09-24

0000-00-00

12

Unspecified

Unspecified

23 Jan 2021

Inclusion Criteria

Age
1 Participant must be ≥ 18 years of age at the time of signing the informed consent.

Type of Participant and Disease Characteristics
2 Histologically or cytologically confirmed R/M SCCHN of the oral cavity, oropharynx, hypopharynx, or larynx who have progressed on or after previous systemic cancer therapy and are not amenable to curative therapy

3 Must have received prior treatment with a systemic PD-(L)1 inhibitor (in any setting)
4 Prior platinum failure as defined by either:
 Disease progression during or after treatment with a platinum-containing regimen for R/M disease or
 Recurrence/progression within 6 months of the last dose of platinum as part of multimodal therapy for LA disease
5 Received 1 or 2 prior systemic regimens for R/M SCCHN 
6 At least one lesion that qualifies as a RECIST 1.1 TL at baseline Tumor assessment by CT scan or MRI must be performed within 28 days prior to randomization.
7 Provide fresh or recently acquired tumor tissue (≤ 3 months prior to screening) for the purpose of biomarker testing. Tumor tissue collected when previous treatments were still ongoing is not acceptable.
 Tumor tissue beyond the 3-month window and up to 6 months old may be considered with Sponsor consultation provided that no intervening systemic regimen was ongoing.
8 For participants with OPC only: known HPV status prior to randomization 
9 WHO/ECOG PS of 0 or 1 at enrollment
10 Adequate organ function, defined as:
(a) Hemoglobin ≥ 9.0 g/dL
(b) Absolute neutrophil count ≥ 1500/mm3
(c) Platelets ≥ 75,000/mm3
(d) Total bilirubin ≤ 1.5 × institutional ULN. This will not apply to participants with confirmed Gilbert’s syndrome, who will be allowed in consultation with their physician.
(e) Aspartate aminotransferase and ALT ≤ 2.5 × institutional ULN; for participants with hepatic metastases, ALT and AST ≤ 5 × ULN
(f) Measured CrCL ≥ 30 mL/min or calculated CrCL ≥ 30 mL/min as determined by
Cockcroft-Gault (using actual body weight)
o Males:
CrCL(mL/min) = Weight (kg) × (140 - age)
72 × serum creatinine (mg/dL)
o Females:
CrCL (mL/min) = Weight (kg) × (140 - age) × 0.85
72 × serum creatinine (mg/dL)

11 Minimum life expectancy of 12 weeks

Weight
12 Body weight > 30 kg

Sex
13 Male and/or female

Reproduction
14 Negative pregnancy test (“highly effective” urine or serum test) for female participants of childbearing potential.
15 Female participants must be one year post-menopausal, surgically sterile, or using an acceptable method of contraception for the duration of the study (from the time they sign consent) and for 4 months after the last dose of study intervention to prevent pregnancy.
16 Male participants must be surgically sterile or using an acceptable method of contraception for the duration of the study (from the time they sign consent) and for 4 months after the last dose of study intervention to prevent pregnancy in a female partner. Male participants must not donate or bank sperm during the same time period.

Informed Consent
17 Capable of giving signed informed consent as described in Appendix A which includes compliance with the requirements and restrictions listed in the ICF and in this protocol
18 Provision of signed and dated, written ICF prior to any mandatory study specific procedures, sampling, and analyses
19 Provision of signed and dated written informed consent for genetic sample and analysis (optional)
20 Provision of signed and dated written Optional Genetic Research Information informed consent prior to collection of samples for optional genetic research that supports Genomic Initiative

Exclusion Criteria

Medical Conditions
1 Histologically or cytologically confirmed head and neck cancer of any other primary anatomic location in the head and neck not specified in the inclusion criteria including participants with squamous cell carcinoma of unknown primary or non-squamous histologies (eg, nasopharynx or salivary gland)
2 Prior cetuximab therapy (unless it was administered in curative LA setting with radiotherapy and no disease progression for at least 6 months following the last cetuximab dose)
3 Any unresolved toxicity NCI CTCAE ≥ Grade 2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.
 Participants with irreversible toxicity not reasonably expected to be exacerbated by treatment with monalizumab and cetuximab may be included only after consultation with the Medical Monitor.
4 Has carcinomatous meningitis and/or untreated central nervous system metastases identified either on the baseline brain imaging obtained during the screening period or identified prior to signing the ICF. Participants with a history of brainmetastases or with suspected brain metastases at screening must have an MRI (preferred) or CT each preferably with iv contrast of the brain prior to study entry. Participants whose brain metastases have been treated may participate provided they show radiographic
stability (defined as 2 brain images, both of which are obtained after treatment to the brain metastases. These imaging scans should both be obtained at least 4 weeks apart and show no evidence of intracranial progression). In addition, any neurologic symptoms that developed either as a result of the brain metastases or their treatment must have resolved or be stable either, without the use of steroids, or are stable on a steroid dose of ≤ 10 mg/day of prednisone or its equivalent and anticonvulsants for at least 14 days prior to the start of treatment. Brain metastases will not be recorded as RECIST 1.1 TL at baseline.
5 Major surgical procedure (as defined by the investigator) within 28 days prior to the first dose of study intervention. Note: Local surgery of isolated lesions for palliative intent is acceptable.
6 History of allogeneic organ transplantation
7 History of allergic reactions or hypersensitivity attributed to compounds of similar chemical or biologic composition to cetuximab and monalizumab or any of their excipients

8 History of active primary immunodeficiency
9 Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn’s disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves’ disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:
 Participants with vitiligo or alopecia
 Participants with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement
 Any chronic skin condition that does not require systemic therapy
 Participants without active disease in the last 5 years may be included but only after consultation with the Medical Monitor
 Participants with celiac disease controlled by diet alone
10 Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice), hepatitis B (known positive HBV surface antigen [HBsAg] result), hepatitis C
(HCV), or human immunodeficiency virus (positive HIV 1/2 antibodies). Participants with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Participants positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
11 Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, active interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the participant to give written informed consent
12 History of another primary malignancy except for:
 Malignancy treated with curative intent and with no known active disease ≥ 5 years before the first dose of study treatment and of low potential risk for recurrence
 Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
 Adequately treated carcinoma in situ without evidence of disease
 Participants with a history of prostate cancer (tumor/node/metastasis stage) of Stage ≤ T2cN0M0 without biochemical recurrence or progression and who in the opinion of the investigator are not deemed to require active intervention

13 Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥ 500 ms calculated from 3 ECGs (within 15 minutes at 5 minutes apart)


Prior/Concomitant Therapy
14 Any concurrent anticancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (eg, hormone replacement therapy) is allowed.
15 Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, mAbs, or investigational agents) or radiotherapy with curative intent (to more than 30% of the bone marrow or with a wide field of radiation) ≤ 28 days prior to the first dose of study intervention. If sufficient wash-out time has not occurred due to the schedule or PK properties of an anticancer agent, a longer wash-out period will be required, as agreed by the Sponsor and the investigator.
16 Current or prior use of immunosuppressive medication within 14 days before the first dose of study intervention. The following are exceptions to this criterion:
 Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular injection)
 Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
 Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication)
17 Receipt of live attenuated vaccine within 30 days prior to the first dose of study
intervention.
Note: Participants, if enrolled, should not receive live vaccine whilst receiving study intervention and up to 30 days after the last dose of study intervention.

Prior/Concurrent Clinical Study Experience
18 Participation in another clinical study with an investigational product administered in the last 28 days prior to randomization or concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
19 Prior treatment with monalizumab

Other Exclusion

20 Involvement in the planning and/or conduct of the study (applies to both Sponsor staff and/or staff at the study site).

21 Judgment by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions and requirements.
22 Previous study intervention assignment in the present study.
23 For women only - currently pregnant (confirmed with positive pregnancy test) or breastfeeding.
24 Genetics research study (optional):
Exclusion criteria for participation in the optional (DNA) genetics research component of
the study include:
 Previous allogeneic bone marrow transplant
 Transfusion of non-leukocyte-depleted blood or blood components within 120 days of genetic sample collection

Interventional

Monalizumab + Cetuximab

Monalizumab is a first-in-class ICI targeting NKG2A. It is a non-depleting humanized IgG4 mAb that binds with high affinity and specificity to, and blocks the inhibitory activity of the CD94/NKG2A receptor resulting in the stimulation of the cytolytic activity of CD94/NKG2Aexpressing NK cells and CD8+ T cells. Monalizumab is being developed for the treatment of various cancers, including solid tumors and hematologic malignancies either as monotherapy or in combination.

Date Amendment Classification Reason
2021-01-08 Changes to clinical trial and human experience data where this is relevant to the ongoing trials(i.e. altered risk: benefit assessment) Safety related to a clinical trial or human experience with the IND
2021-04-07 Amendments related to the protocol Safety monitoring

Randomized

Double Blind

Unspecified

Parallel

To compare the effect of monalizumab and cetuximab (Arm A) relative to placebo and cetuximab (Arm B) by assessment of OS

Phase III

Utilization Utilization Info
Publication
Oral Presentation
Drug Literature
Posters
Others
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