A Phase 1, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Antitumor Activity of MEDI5752 in Subjects with Advanced Solid Tumors
- Conditions
- Advanced solid tumors: subjects withclear-cell renal cell carcinoma (referred to as RCC expansion cohort) and subjects with first-lineStage IIIB or IV nonsquamous non-small cell lung cancer (NSCLCreferred to as NSCLC expansion cohort). = renal cell carcinoma and nonsquamous non-small cell lung cancer10027656
- Registration Number
- NL-OMON54211
- Lead Sponsor
- MedImmune, LLC, a wholly owned subsidiary of AstraZeneca PLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 10
General criteria applicable to the entire population enrolled in the study: 1
Age >= 18 years at the time of screening 2 World Health Organization/Eastern
Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrollment 3
Life expectancy >= 12 weeks 4 Histologically- or cytologically-confirmed
advanced solid tumors 5 Body weight (WT) > 35 kg 6 Subjects who have received
prior anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapy or any prior chemotherapy,
investigational, biologic, or hormonal therapy for cancer treatment may be
eligible to enter the study (see inclusion criterion #20 [RCC-C1] and #28
[RCC-C2] for requirements for RCC expansion cohorts and #25 for requirements
for NSCLC expansion cohorts) [NSCLC-C1 and NSCLC-C2]) following a washout
period of these treatments of at least 21 days before the first dose; 7 day
washout period is required for palliative radiotherapy (exception: 14-day
washout period for central nervous system [CNS] metastases) and washout period
of 5 half-lives is required for TKIs before the first dose; 7 Females of
childbearing potential who are sexually active with a nonsterilized male
partner must use at least one highly effective method of contraception (See
Table 27 in the protocol for recommended methods of contraception) from
screening and must agree to continue using such precautions for the specified
number of days after the final dose of investigational product: (a) MEDI5752:
90 days (b) Carboplatin: 90 days (c) Pemetrexed: 180 days (d) Pembrolizumab:
120 days (e) Paclitaxel: 6 months (ie, 180 days) (f) Nab-paclitaxel: 6 months
(ie, 180 days) See protocol for definition of Females of childbearing potential
definition. 8 Nonsterilized males who are sexually active with a female partner
of childbearing potential must use a male condom with spermicide where locally
available from Day 1 and for 90 days after the final dose of investigational
product. Males receiving pemetrexed, carboplatin, paclitaxel, or nab-paclitaxel
treatment must use contraception during study treatment and up to 6 months
thereafter. Male subjects should refrain from sperm donation throughout this
period. It is strongly recommended that the female partner of childbearing
potential to use at least one highly effective method of contraception (see
protocol). Not engaging in sexual activity is an acceptable practice; however,
occasional abstinence, the rhythm method, and the withdrawal method are not
acceptable methods of contraception. 9 Subjects must have at least one
measurable lesion according to RECIST v1.1. A previously irradiated lesion can
be considered a target lesion if the lesion is progressing and well defined,
accurately measured at baseline as being >= 10 mm in the longest diameter
(except lymph nodes, which must have a short axis >= 15 mm) with CT or magnetic
resonance imaging (MRI), and that is suitable for accurate repeated
measurements as per RECIST v1.1 guidelines. Subjects must consent to providing
the prior CT scan or MRI before enrolling in the study. Radiographic disease
assessment at baseline can be performed up to 28 days prior to the first dose
of investigational product. For subjects who undergo biopsies on study, the
biopsied lesion must be distinct from any lesion used in the RECIST evaluation.
10 Adequate organ and marrow funct
1 Involvement in the planning and/or conduct of the study (applies to both
MedImmune staff and/or staff at the study site) 2 Concurrent enrollment in
another clinical study, unless it is an observational (noninterventional)
clinical study or the follow-up period of an interventional study 3 Any prior
Grade >= 3 imAE while receiving immunotherapy or any unresolved imAE > Grade 1 4
For subjects who have received prior anti-PD-1, anti-PD-L1, or anti-CTLA-4: (a)
Subjects must not have received anti-PD-1, anti-PD-L1, anti-CTLA-4 or any other
immunotherapy or IO agent within 21 days of commencing treatment with
investigational product. (b) Subject must not have experienced a toxicity that
led to permanent discontinuation of prior immunotherapy. (c) All AEs while
receiving prior immunotherapy must have completely resolved or resolved to
Grade 1 prior to screening for this study. NOTE: Subjects with an endocrine AE
of <= Grade 2 are permitted to enroll if they are stably maintained on
appropriate endocrine replacement therapy and are asymptomatic. (d) Subject
must not have experienced a >= Grade 3 imAE or an immune-related neurologic or
ocular AE of any grade while receiving prior immunotherapy. NOTE: Subjects with
endocrine AE of <= Grade 2 are permitted to enroll if they are stable on
appropriate replacement therapy and are asymptomatic. (e) Subject must not have
required the use of additional immunosuppression other than corticosteroids for
the management of an AE, must not have experienced recurrence of an AE if
rechallenged, and must not currently require maintenance doses of > 12 mg
prednisone or equivalent per day. 5 Any concurrent chemotherapy, radiotherapy,
investigational, biologic, or hormonal therapy for cancer treatment (see
Inclusion Criterion 6 for washout periods [Section 4.1.2]). Concurrent use of
hormonal therapy for noncancer-related conditions (eg, insulin for diabetes and
hormone replacement therapy) is acceptable. NOTE: Local treatment of isolated
lesions for palliative intent is acceptable (eg, metastasis treated by local
surgery or radiotherapy) 6 Current or prior use of immunosuppressive medication
within 14 days before the first dose of investigational product is excluded.
The following are exceptions to this criterion: (a) Intranasal, inhaled,
topical steroids, or local steroid injections (eg, intraarticular injection)
(b) Steroids as premedication for hypersensitivity reactions (eg, CT scan
premedication) or a single dose for palliative purpose (eg, pain control) 7
Receipt of live attenuated vaccine within 30 days prior to the first dose of
investigational product. Note: Subjects, if enrolled, should not receive live
vaccine while receiving investigational product and up to 30 days after the
last dose of investigational product. 8 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, pneumonitis (past medical history of ILD, drug induced
ILD. Radiation pneumotitis requiring steroid treatment or any evidence of
clinically active ILD),etc). The fol
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Endpoints (Dose-escalation Phase):<br /><br>• Safety will be assessed by the presence of adverse events (AEs), serious<br /><br>adverse events (SAEs), DLTs, and abnormal laboratory parameters, vital signs,<br /><br>and electrocardiogram (ECG) results.<br /><br>• The MTD will be determined by DLTs during the dose-escalation phase. The OBD<br /><br>will be determined from the safety, efficacy, PK, pharmacodynamic, and<br /><br>biomarker data.<br /><br><br /><br>Primary Endpoints (Dose-expansion Phase Parts 1 and 2):<br /><br>• Assessment of antitumor activity based on OR using RECIST v1.1 .<br /><br><br /><br>Primary Endpoints (Dose-expansion Phase Part 3):<br /><br>• Safety will be assessed by the presence of AEs, SAEs, abnormal laboratory<br /><br>parameters, vital signs, and ECG results.<br /><br><br /><br>Please refer to protocol for exploratory end points</p><br>
- Secondary Outcome Measures
Name Time Method