Study of Avelumab-M3814 Combinations



Status:Recruiting
Conditions:Cancer, Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:18 - Any
Updated:2/23/2019
Start Date:November 27, 2018
End Date:July 28, 2021
Contact:US Medical Information
Email:service@emdgroup.com
Phone:888-275-7376

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A Multicenter, Open-Label, Dose Escalation Phase I Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of the DNA-PK Inhibitor M3814 in Combination With Avelumab With and Without Palliative Radiotherapy in Participants With Selected Advanced Solid Tumors

The main purpose of the study is to evaluate a safe, tolerable recommended Phase II dose
(RP2D) and/or the maximum tolerated dose (MTD) of M3814 when given in combination with
avelumab with and without radiotherapy in participants with selected advanced solid tumors.


Inclusion Criteria:

- Part A (M3814 + avelumab): Participants must have histologically or cytologically
proven advanced or metastatic solid tumors for which no standard therapy exists,
standard therapy has failed, or participants are intolerant to or have rejected
established therapy known to provide clinical benefit for their condition

- Part B (M3814 + Radiotherapy [RT] + avelumab): histologically or cytologically proven
advanced or metastatic solid tumors with primary tumors or metastatic tumor lesions in
the lung for which no standard therapy exists, standard therapy has failed, or
participants are intolerant to or have rejected established therapy known to provide
benefit for their condition and are amenable to receive RT to the tumor in the lung

- Part A and B: Measurable or evaluable disease according to RECIST v 1.1

- Part A and B: Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to
1 at study entry Demonstrate adequate organ function including bone marrow, liver and
kidney based on blood tests within 28 days of first dose of study therapy)/ Have
provided tissue from an archival tissue sample or newly obtained tissue sample

- Part A and B: Female participants of childbearing potential should be willing to use a
highly effective contraceptive method or be surgically sterile, or abstain from
heterosexual activity for the course of the study through 90 days after the last dose
of study medication

- Part A and B: Male participants should agree to refrain from donating sperm and use an
adequate method of contraception starting with the first dose of study therapy through
90 days after the last dose of study therapy

- Part A and B: Be willing to provide informed consent for the trial

- Other protocol defined inclusion criteria could apply

Exclusion Criteria:

- Participants who have received prior chemotherapy, hormonal anticancer therapy with
the exception of luteinizing hormone-releasing hormone analogs, biologic therapy, or
any other anticancer therapy within 4 weeks prior to the first dose of study
treatments (6 weeks for nitrosoureas or mitomycin C)

- Participants who have undergone major surgery for any reason, except diagnostic
biopsy, within 4 weeks of the study intervention and/or have not fully recovered from
the surgery within 4 weeks of the study intervention

- Participants with evidence of active or history of autoimmune disease that might
deteriorate when receiving an immune-stimulatory agent

- Participants with evidence of active central nervous system (CNS) metastases.
Participants with previously treated brain metastases may participate provided the
brain metastases are stable for at least 4 weeks prior to the first dose of study
treatments and they are either off steroids or on a stable or decreasing dose of less
than (<) 10 milligram (mg) daily prednisone (or equivalent)

- Participants with severe acute or chronic medical conditions including immune colitis,
inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric
conditions including recent (within the past year), psychiatric or substance abuse
disorders; or laboratory abnormalities that might confound trial results, interfere
with the patient's participation or is not in the best interest of the participant

- Participants requiring systemic immunosuppressive treatment (such as steroids) for any
reason who cannot be tapered off these drugs before start of study treatment.
Participants with adrenal insufficiency, may continue corticosteroids at physiologic
replacement dose, patients requiring steroids through a route known to result in a
minimal systemic exposure (topical, intranasal, intra-ocular, or inhalation) or
participants with Previous or ongoing administration of systemic steroids for the
management of an acute allergic phenomenon planned to be completed in 14 days, or that
the dose after 14 days will be equivalent to less than or equals to (<=) 10 mg
prednisone daily may participate

- Participants with a history of human immunodeficiency virus (HIV), HIV 1/2 antibodies
or known acquired immunodeficiency syndrome, Hepatitis B or Hepatitis C

- Participants who have received a live vaccine within 30 days prior to the first dose
of trial treatment

- Participants with known prior severe hypersensitivity to any of the investigational
products or any component in its formulations

- Participants with evidence of additional malignancy within the last 5 years unless a
complete remission without further recurrence was achieved at least 2 years prior to
study entry and patients were deemed to have been cured with no additional therapy
required or anticipated to be required. Patients with treated nonmelanoma skin
cancers, carcinoma in situ of skin, bladder, cervix, colon/rectum, breast, or prostate
may participate

- Participants pretreated with immunotherapy who have, any history of toxicities with
prior immunotherapy agents, including Grade 3/4 immune-related adverse events (irAEs);
irreversible irAEs; Grade greater than or equals to (>=) 3 irAEs that did not respond
to steroid rescue; or neurologic irAE with significant clinical sequelae

- Participants with irAE requiring hormone replacement therapy (e.g., thyroxine,
insulin, or physiologic dose of corticosteroid replacement therapy for adrenal or
pituitary insufficiency) may participate as long as the endocrinopathy is well
controlled and the participant is not otherwise symptomatic from hormone insufficiency

- Physiologic corticosteroid dose is defined as <= 10 mg daily of prednisone or
equivalent

- Participants who are pregnant / breastfeeding or expecting to conceive within the
duration of the trial, starting with the screening visit through 90 days after the
last dose

- for Part B only:

- Participants who have confirmed esophagitis and in whom radiation planning target
volume will include any portion of the esophagus

- Participants in whom more than 10 percent (%) of the total esophagus might receive
more than 15 Gy (50% of the prescribed RT dose)

- Participants who have had previous radiotherapy to the same region as intended to be
irradiated in this study within the past 12 months Participants who have had extensive
previous radiotherapy on >= 30% of bone marrow reserve or prior bone marrow/stem cell
transplantation within 5 years before study start

- Other protocol defined exclusion criteria could apply
We found this trial at
4
sites
12902 USF Magnolia Dr
Tampa, Florida 33612
(888) 663-3488
H. Lee Moffitt Cancer Center & Research Institute Moffitt Cancer Center in Tampa, Florida, has...
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5841 S Maryland Ave
Chicago, Illinois 60637
(773) 702-1000
University of Chicago Medical Center The University of Chicago Medicine has been at the forefront...
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Nashville, Tennessee 37205
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