Study of MGC018 Alone and in Combination with MGA012 in Patients with Advanced Solid Tumors

Phase 1

• Conditions: MedDRA version: 21.1Level: LLTClassification code 10065147Term: Malignant solid tumorSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Advanced Solid Tumors; MedDRA version: 21.1Level: PTClassification code 10067821Term: Head and neck cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: LLTClassification code 10036921Term: Prostate carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: LLTClassification code 10040891Term: Skin melanomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]; MedDRA version: 20.0Level: PTClassification code 10075566Term: Triple negative breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: LLTClassification code 10065252Term: Solid tumorSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

• Registration Number: EUCTR2018-003555-38-PL
• Lead Sponsor: MacroGenics, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-06-12
• Last Update Posted: 7 June 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 182

Inclusion Criteria

1. Ability to provide informed consent and documentation of informed consent prior to initiation of any study-related tests or procedures that
are not part of standard-of-care for the participant's disease. Participants must also be willing and able to comply with study procedures, including the acquisition of specified research specimens.
2. Age = 18 years old.
3. Archival or FFPE tissue must be available for determination of B7-H3 (Module A) and B7-H3 and PD-L1 expression (Module B). Participants
may undergo a fresh tumor biopsy to obtain a specimen for testing if a tumor sample is not available; mCRPC with bone only disease not amenable to fresh biopsy may be eligible in consultation with the sponsor.
4. Eastern Cooperative Oncology Group (ECOG) performance status of =2.
5. Life expectancy = 12 weeks for Dose Escalation Phase and = 24 weeks for Cohort Expansion Phase.
6. Measurable disease as per RECIST v1.1 criteria. Participants with mCRPC without measurable disease may be enrolled. Cutaneous or
subcutaneous lesions must be measurable by calipers. Note: Lesions to be used as measurable disease for the purpose of response assessment
must not reside in a field that has been subjected to prior radiotherapy
or.
7. Tumor Histology Types
Dose Escalation Phase of the Study:
a) Participants with histologically proven, relapsed or refractory, unresectable locally advanced or metastatic solid tumors of any histology for whom no therapy with demonstrated clinical benefit is available.
Cohort Expansion Module A:
a) mCRPC that has progressed during or following one prior line of chemotherapy for metastatic disease, and if approved and available, no
more than two prior lines of an anti-hormonal agent (e.g., abiraterone, enzalutamide) with a PSA value of at least 2 ng/mL and meeting at least
one of the following:
• Progression in measurable disease (RECIST v1.1).
• Appearance of 2 or more new bone lesions according to Prostate Cancer Working Group 2 (PCWG2).
• Rising PSA defined as at least two sequential rises in PSA (PSA obtained = 1 week apart) over a reference value (the last PSA [PSA = 2 ng/mL] measured before the first rise in PSA) (as defined by the PCWG2).
b) NSCLC
• Metastatic NSCLC who have failed standard cytotoxic, targeted, and biologic or checkpoint inhibitor therapy. No more than two prior lines of
cytotoxic chemotherapy.
c) TNBC
• Locally advanced or metastatic TNBC that has progressed during or following at least one systemic therapy. American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) guidelines should be followed for establishing the diagnosis of TNBC.
d) SCCHN that has progressed during or following at least one systemic therapy for metastatic or recurrent unresectable disease. No more than 2 prior lines of cytotoxic chemotherapy are allowed.
e) Melanoma that has progressed during or following at least one systemic treatment for unresectable locally advanced or metastatic disease. Patients who are intolerant of or refused standard therapy are eligible.
Cohort Expansion Module B:
Participants with histologically proven, unresectable, locally advanced or metastatic solid tumors for whom no therapy with demonstrated clinical
benefit is available as described below.
a) SCCHN that has progressed following treatment with platinum-based chemotherapy for metastatic or recurrent disease, or progression of disease within 6 months of completing prior platinum therapy used as part of neoadjuvant, concurre

Exclusion Criteria

1. Participants with history of prior central nervous system (CNS) metastasis must have been treated, must be asymptomatic, and must
not have any of the following at the time of enrollment:
- Concurrent treatment for the CNS disease (e.g., surgery, radiation, corticosteroids > 10 mg prednisone/day or equivalent)
- Progression after primary treatment of CNS metastases on imaging with MRI, CT or positron emission tomography (PET)/CT within 6 months prior to screening.
- History of leptomeningeal disease or spinal cord compression.
2. Module B only: Participants with any history of known or suspected autoimmune disease with the specific exceptions of vitiligo, resolved childhood atopic dermatitis, psoriasis not requiring systemic treatment (within the past 2 years), and participants with a history of Grave’s disease that are now euthyroid clinically and by laboratory testing.
3. Treatment with any, investigational therapy within the 4 weeks prior to the initiation of study drug administration.
4. Module B only: Previous Checkpoint Inhibitor Therapy: Patients who experienced the following immune checkpoint inhibitor-related AEs make the patient ineligible despite the AE resolving to = Grade 1 or baseline:
o = Grade 3 ocular AE
o Changes in liver function tests that met the criteria for Hy's Law (> 3 × ULN of either ALT/AST with concurrent > 2 × ULN of total
bilirubin and without alternate etiology)
o = Grade 3 neurologic toxicity
o = Grade 3 colitis
o = Grade 3 pneumonitis
o = Grade 3 renal toxicity
o = Grade 3 skin toxicity
5. Prior treatment with MGD009, enoblituzumab, or other B7-H3 targeted agents for cancer.
6. Treatment with any systemic anti-cancer therapy within the interval specified in the protocol
7. Treatment with mediastinal or pelvic radiation therapy within 4 weeks prior to the minitiation of study drug administration. Palliative, limited
field radiation for symptom control to soft tissues, or bone lesions within 2 weeks prior to the initiation of study drug administration.
8. Module B only: Treatment with systemic corticosteroids (> 10 mg per day prednisone or equivalent) or other immune suppressive drugs within the 14 days prior to the initiation of study drug administration.
9. Clinically significant cardiovascular diseases.
10. Clinically significant pulmonary compromise, including pneumonia, pneumonitis, or a requirement for supplemental oxygen use to maintain adequate oxygenation or history of = Grade 3 drug-induced or radiation pneumonitis.
11. Evidence of active viral, bacterial, or systemic fungal infection requiring parenteral antibiotic, antiviral, or antifungal treatment within 7 days prior to the initiation of study drug. Participants requiring any systemic antiviral, antifungal, or antibacterial therapy for active infection must have completed treatment no less than one week prior to the initiation of study drug.
12. Known history of positive testing for human immunodeficiency virus or history of acquired immune deficiency syndrome.
13. Known history of hepatitis B or hepatitis C infection or known positive test for hepatitis B surface antigen, hepatitis B core antigen, or hepatitis C polymerase chain reaction.
14. History of prior allogeneic bone marrow, stem-cell, or solid organ transplantation.
15. Second primary invasive malignancy that has not been in remission for greater than
2 years except non-melanoma skin cancer; cervical carcinoma in situ on biopsy; or squamous intraepithelial lesion on Pap smear; lo

Study & Design

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