Participants may not have had prior use of PARP inhibitors; patients may not have received prior treatment affecting the VEGF pathway including but not limited to thalidomide, bevacizumab, sunitinib, or sorafenib
Prior treatment with any VEGF inhibitor
Not previously received XL184 or another MET/HGF inhibitor (tivantinib or crizotinib); there are no limits on number of prior therapeutic regimens; patients who have been treated with prior VEGF pathway, or RET inhibitors (except XL184) may be eligible
Received any anti-cancer drug known to have anti-VEGF/VEGFR activity within a period of 5 half-lives of this drug (e.g. 100 days for bevacizumab, 75 days for ramucirumab) prior to the first scheduled dose of MM-310
Received any previously systemic therapy (including investigational agents) targeting VEGF or the VEGFR signaling pathways; other previous targeted therapies are permitted if stopped at least 28 days prior to start of treatment
Subjects may have received bevacizumab, VEGF-Trap, or other VEGF blocking tyrosine kinase inhibitors, provided that they did not progress while receiving one of these agents. Subjects may not have previously received pazopanib.
At least 21 days must have elapsed since the completion of the last dose of VEGF-Trap, and at least 7 days since a VEGF blocking tyrosine kinase inhibitor. Subjects must have recovered from any VEGF blocking drug-related toxicity (e.g., proteinuria).
Participants who have already received anti-VEGF or experimental antiangiogenic therapy for glioblastoma
Prior treatment with bevacizumab or other direct VEGF/ VEGFR inhibitors. For any question of the definition of a direct VEGF/VEGFR inhibitor, consult Sponsor.
No more than two prior regimens targeting the VEGF pathway; no prior bevacizumab therapy
Having progressed on at least one prior line of therapy, histologically or cytologically confirmed diagnosis of one of the following: \r\n* Dose escalation and expansion cohorts:\r\n** Checkpoint inhibitor naive non-small cell lung cancer patients must have progressed on front-line therapy cytotoxic chemotherapy and may have received up to two prior treatment regimens provided no regimens included an anti-PD1 or PD-L1 agent or an oral VEGF TKI. Prior bevacizumab or ramucirumab is allowed.\r\n** Progressed on checkpoint inhibitor non-small cell lung cancer patients must have progressed on front-line checkpoint inhibitor therapy and may have received up to two prior treatment regimens provided no regimens included an oral VEGF TKI. Prior bevacizumab or ramucirumab is allowed.\r\n** Thymic carcinoma patients must not be eligible for surgical resection at the time of enrollment and may have received any number of prior lines of therapy provided no regimens included an anti-PD1 or PD-L1 agent or an oral VEGF TKI. Prior bevacizumab or ramucirumab is allowed.
Patients currently on cytotoxic chemotherapy or immunotherapy are eligible, not including anti-VEGF therapy
Must have progression of disease within 6 months of study enrollment after treatment with only one of the following:\r\n* Two prior lines of therapy: a VEGF inhibitor (other than axitinib), followed by a single agent PD-1/PDL-1 antibody, or\r\n* One prior line of therapy: combination of a VEGF inhibitor (other than axitinib) AND a PD1/PDL1 antibody, or
Has received anti-angiogenic or anti-VEGF targeted agents (e.g. bevacizumab, cediranib, aflibercept, vandetanib, XL-184, sunitinib, etc)
Clear cell subject: must have received at least 2 prior systemic regimens, one of which is an anti-VEGF agent.
Non-clear cell subject: must have received at least one prior anti-VEGF regimen
Subjects may have received up to 2 prior lines of systemic therapy (excluding any neoadjuvant/adjuvant therapy) including anti-VEGF or VEGFR inhibitor (e.g. sorafenib, pazopanib, sunitinib, bevacizumab, axitinib) or mTOR inhibitor (e.g. everolimus or temsirolimus) for metastatic disease
Prior therapy with axitinib and/or sunitinib as well as any prior therapies with other VEGF pathway inhibitors
PHASE II: No more than two prior VEGF-pathway targeted agents
Use of VEGF inhibitors within 10 days prior to registration
Prior treatment with agents targeting the VEGF pathway, including bevacizumab
Participants who have received anti-VEGF targeted agents (e.g. bevacizumab, cediranib, aflibercept, vandetanib, XL184, sunitinib etc)
Prior treatment affecting the VEGF/VEGFR pathway or the angiopoietin pathway in the recurrent setting, including but not limited to thalidomide, bevacizumab, sunitinib, sorafenib, pazopanib, cediranib, nintedanib, and trebananib; bevacizumab used in the upfront setting in conjunction with chemotherapy and/or as maintenance to treat newly diagnosed disease will be allowed
Part 2: Progression of disease following one VEGF pathway inhibitor for RCC (e.g. sunitinib, pazopanib, sorafenib, bevacizumab, tivozanib, or cabozantinib) inclusive of adjuvant therapy if there was documented disease progression during treatment. Patients may have received one additional line of an approved mTOR kinase inhibitor (e.g. everolimus, temsirolimus). Prior exposure to investigational and/or approved anticancer immune therapies is permitted.
Prior treatment:\r\n* No radiotherapy within 90 days prior to pre-registration\r\n* No prior treatment with any anti-angiogenic agent targeting the vascular endothelial growth factor (VEGF) pathway including but not limited to bevacizumab, cediranib, vandetanib, sunitinib, pazopanib, aflibercept or sorafenib\r\n* No prior treatment with HSPPC-96 or other investigational immunotherapy\r\n* Must have received prior treatment with radiotherapy and temozolomide for histologically confirmed GBM at initial diagnosis\r\n* No tumor directed therapy for most recent progression\r\n* No prior Gliadel wafers
Prior exposure to bevacizumab or other VEGF- or VEGF-receptor-targeted agent within 8 weeks of study start.
Prior anti-angiogenic therapy including VEGF sequestering agents (i.e. bevacizumab, aflibercept, etc.) or VEGFR inhibitors (cedirinib, pazopanib, sunitinib, sorafenib, etc.);
Subjects must have received their last chemotherapy, non-anti-VEGF biologic, or investigational therapy at least 4 weeks prior to enrollment, 6 weeks if the last regimen included BCNU or mitomycin C, and 8 weeks if the last regimen was an anti-VEGF therapy
Subjects who have received an anti-DLL4 antibody, or an anti-DLL4/VEGF bispecific antibody Subjects who have received prior anti-VEGF therapy are eligible, unless they have residual serious adverse events related to their anti-VEGF therapy.
At least 1, prior line of VEGF-targeted therapy, but not more than 4 total prior lines of systemic therapy. Exposure to more than 1 line of VEGF-targeted therapy is acceptable. Participants may also have received prior therapies with interferon, interleukin 2 (IL-2), anti-PD1 antibodies, cabozantinib or other experimental agents, but not prior therapy with any agent that targets phosphoinositide 3-kinase (PI3K), serine/ threonine-specific protein kinase (AKT), or mechanistic (or mammalian) target of rapamycin (mTOR).
Subject received prior systemic treatment for HCC with sorafenib or other anti-VEGF therapy and had confirmed disease progression or discontinued treatment due to a drug-related toxicity. Subject may have received 1 line of systemic therapy before or after sorafenib/anti-VEGF treatment.
Prior therapy with axitinib as well as any prior therapies with other VEGF pathway inhibitors.
Prior systemic treatment with VEGF or VEGF receptor targeted therapy (including, but not limited to, Sunitinib, Pazopanib, Axitinib, Tivozanib, and Bevacizumab)
Prior anti-VEGF directed therapy may be allowed only if approved by the principle investigator (PI)
Vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR)-targeted or mammalian target of rapamycin (mTOR)-targeted therapies: Must not have received prior exposure to lenvatinib; May have previously progressed on an mTOR inhibitor; No more than 2 prior VEGF/VEGFR-targeted therapies (For Phase 2 only); Must not have received prior VEGF/VEGFR-targeted therapy in combination with an mTOR inhibitor (For Phase 2 only)
Patients must have documented radiologic or clinical progressive disease following at least one prior anti-VEGF regimen administered either as a single agent or in combination with other agents for at least 8 weeks; the prior anti-VEGF treatment regimen must have included bevacizumab, pazopanib, sorafenib or sunitinib administered not more than 12 weeks before study entry; Note: enrollment not more than 8 weeks after the last dose of anti-VEGF therapy is encouraged; nevertheless, intercurrent therapy with an mTOR inhibitor (everolimus or temsirolimus) will be allowed if progression on that treatment is observed within 12 weeks of the prior anti-VEGF therapy
Prior use of an investigational drug that targets VEGF or VEGF receptors
Patients must have recurrent disease and may have had any number of prior relapses (including no prior relapses) on NON-anti-vascular endothelial growth factor (VEGF)(receptor [R]) containing regimens; relapse is defined as progression following initial therapy; for patients who progressed on a prior anti-VEGF(R) containing regimen including bevacizumab, only one prior relapse on an anti-VEGF(R) containing regimen is allowed
Patients with one prior relapse on a bevacizumab or an anti-VEGF(R) (i.e., VEGF-trap, vandetanib, cediranib, sunitinib, sorafenib, XL184, etc.) containing regimen are allowed to participate
Patients who have received prior therapy with any anti-VEGF drug, including bevacizumab.
If patients have been treated with anti-VEGF agents, such as bevacizumab, last dose must be >= 4 weeks
Have received at least one prior course of treatment for ccRCC. Part C only: Prior treatment must include at least 1 course of VEGF-directed therapy.
Any number of prior lines of systemic anti-neoplastic therapy are allowed; treatment with =< 1 prior VEGF inhibitor will be allowed
Prior adjuvant therapy with sorafenib or another Raf/VEGF inhibitor
Prior treatment with sorafenib or other RAF/VEGF targeted therapies.
The immediate prior treatment regimen must have included an anti-VEGF agent; acceptable anti-VEGF therapy includes bevacizumab, ziv-aflibercept, sunitinib, or sorafenib; for other anti-VEGF therapies, contact the principal investigator
Any prior exposure to any VEGF or VEGF inhibitor including, but not limited to, bevacizumab, cediranib, vandetanib, sunitinib, pazopanib, aflibercept, or sorafenib (Phase II)
Patients must not have received prior treatment with any VEGF receptor tyrosine kinase inhibitor (e.g., cediranib, sunitinib, pazopanib, sorafenib); however, prior treatment with bevacizumab is allowed
Prior therapy against VEGF or VEGFRs including, but not limited to bevacizumab, sunitinib, sorafenib, pazopanib, motesanib (AMG706), or cediranib (AZD2171), is permitted so long as the agent does not have any known activity against DLL4 and the last dose received s at least 6 weeks prior to first dose of MEDI0639.
Prior use of other investigational or licensed tyrosine kinase inhibitors (TKIs), or agents which target VEGF or VEGF receptors (i.e., bevacizumab, VEGF-Trap)
COHORT 2 ONLY: Prior treatment with a VEGF inhibitor (e.g. sunitinib, bevacizumab, sorafenib or other dedicated VEGF inhibitor)
COHORT 1 ONLY: Prior treatment with a VEGF inhibitor (e.g. sunitinib, bevacizumab, sorafenib or other dedicated VEGF inhibitor)
Patient must not have undergone therapy with any VEGF monoclonal antibodies in the last twelve weeks; patient must not be receiving any small molecule anti-VEGF drug within previous 4 weeks
Participants who have already received anti-VEGF or investigational anti-angiogenic therapy for glioblastoma
Participants who have received any treatment regimen including a VEGF-R inhibitor such as bevacizumab or cediranib, or plan to receive such agents as part of initial management for glioblastoma
Subjects must be planned for treatment with approved treatment doses of a VEGF receptor TKI (e.g., sunitinib, pazopanib, cabozantinib, axitinib, sorafenib, lenvatinib)