Safety and tolerability of MEDI4736 in Combination With AZD9150 or AZD5069 in solid tumors and subsequently evaluating AZD9150 or AZD5069 as single agent or in combinations with MEDI4736 in Patients with recurrance or spread of Squamous Cell Carcinoma of the Head and Neck

Phase 1

• Conditions: Part A (US ONLY): advanced solid malignancies Part B (NA, EU): Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck; MedDRA version: 20.0Level: LLTClassification code 10065147Term: Malignant solid tumorSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10060121Term: Squamous cell carcinoma of head and neckSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2015-002525-19-DE
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-09-28
• Last Update Posted: 12 October 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 335

Inclusion Criteria

-Eastern Cooperative Oncology Group performance status score of 0 or 1
-Measurable disease
-Male and female above 18 years
- Undergone 1-3 previous regimens (B1-B6) of cytoreductive therapies including, but not limited to, platinum-based compounds, taxanes, or 5-
fluorouracil. For patients in Arm B7 & B8 no prior systemic treatment should have been received for RM SCCHN
-Adequate organ and marrow function
-Women of childbearing potential and men who are sexually active with a female partner of childbearing potential must prevent pregnancy and
women may not be breast feeding

Additional inclusion criteria for Part A:
-Histological confirmation of a solid malignancy (other than HCC) refractory to standard therapy or for which no standard of care regimen currently exists.
Additional inclusion criteria Arm A6 of Part A
-Has a histological confirmation of castrate-resistant prostate cancer

Additional inclusion criteria for Part B:
-Histologically and/or cytologically confirmed SCCHN that is RM and not amenable to curative therapy by surgery or radiation. Squamous cell
carcinoma of the head and neck originating from the following sites is eligible: oral cavity, oropharynx, larynx, or hypopharynx.
-Has at least 1 SCCHN tumour lesion (TL) amenable to biopsy and must be medically fit and willing to undergo a biopsy during screening and,
unless clinically contraindicated, at the end of Cycle 1.
-Must have failed for least 1 prior platinum-based chemotherapy for RMSCCHN (B1-B6)
-Must have received no prior systemic therapy for RM SCCHN (B7 & B8)

Additional inclusion criteria for Part B, arms B1 & B2
Has had prior exposure to any anti PD (L)1 antibody

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 167
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 168

Exclusion Criteria

-Symptomatic spinal cord compression
-Second malignancy
-Concurrent chemotherapy, radiotherapy, immunotherapy and/or investigational anticancer therapy, or biologic or hormonal therapy for cancer
-Ongoing toxicity related to prior treatment and assessed as grade >1 Immune-related adverse events (AEs) while receiving prior immunotherapy (including anti-cytoxic T-lymphocyte-associated protein 4 treatment) and assessed as grade =3
-Has active or prior documented autoimmune disease within the past 2 years with the exception of vitiligo, Grave’s disease, and/or psoriasis not requiring systemic treatment
-Active or prior documented inflammatory bowel disease
-History of primary immunodeficiency
-Prior organ transplant that requires use of immunosuppressive treatment
-Cardiac conditions that render the patient unsuitable for participation in the study
-Inability to take oral medications and/or has a clinical or radiological diagnosis of bowel obstruction
-History of allergic reactions attributed to the study treatments (AZD9150, AZD5069, or MEDI4736 or treme (Part A)), their compounds, or agents of similar chemical or biologic composition
-Suffers from a comorbidity that in the opinion of the Investigator renders the patient unsuitable for participation in the study
-As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases such as active bleeding diatheses, or is positive for human immunodeficiency virus (HIV), hepatitis B virus (HBV), and/or hepatitis C virus (HCV)
-History of tuberculosis
-Condition that, in the opinion of the Investigator, would interfere with the evaluation of the study drugs or the interpretation of patient safety or study results
-Live attenuated vaccine within 28 days before the first dose of study drug
-Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements.
-Patients with brain metastases considered stable may be enrolled into Part A of the study; they are excluded form Part B of the study
-Patients must not be included in the optional genetic research if they have previously received an allogeneic bone marrow transplant or have received non-leukocyte depleted whole blood transfusion(s) within 120 days before the date of the genetic sample collection

Additional exclusion criteria for Part A:
-Patients with clinically active brain metastases (known or suspected) are excluded
unless the brain metastases have been previously treated and are considered stable.
Stable brain metastases are defined as no change on CT scan or magnetic resonance
imaging (MRI) scan for a minimum of 2 months AND no change in steroid dose for
a minimum of 4 weeks, unless change due to intercurrent infection or other acute
event.
- Has had prior exposure to AZD9150, AZD5069, MEDI4736, or any other anti PD (L)1 antibody.

Additional exclusion criteria for Part B:
Patients with brain metastases (known or suspected) are excluded

Additional exclusion criteria Part B: treatment arms B3, B4, B5, B6, B7 and B8
Has had prior exposure to AZD9150, AZD5069, MEDI4736, or any other anti PD (L)1 antibody.

Study & Design

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