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The PD\u20101\/PD\u2010L1 pathway is a T\u2010cell co\u2010inhibitory pathway that normally maintains immune tolerance to self. Its role in pregnancy is to maintain immune tolerance to the fetal allograft. In cancer patients, this signaling pathway is hijacked by some neoplasms to avoid immune destruction. PD\u20101\/PD\u2010L1\u2010blocking agents enhance functional activity of the target lymphocytes to eventually cause immune rejection of the tumor. A therapeutic blockade of PD\u20101\/PD\u2010L1 pathway that occurs at full target engagement provides a unique challenge to address the risk to pregnancy because disruption of the same pathway may also reduce or abrogate maternal immune tolerance to the fetal alloantigens inherited through the father. Typically, nonclinical reproductive and developmental toxicity (DART) studies in animals (rats and rabbits) with clinical drug candidates are conducted to identify potential risk in humans and to determine exposure margin for the effects on reproduction as part of the risk assessment. However, for biopharmaceuticals for which the desired mechanism of action cannot be separated from potential deleterious effects to the fetus and when the only relevant toxicology species is nonhuman primate (NHP), the risk to reproduction can be predicted by a mechanism\u2010based assessment using data generated from murine surrogate models as supportive information without conducting DART in NHPs. Such an approach has been used in the evaluation of pregnancy risk of anti\u2010PD\u20101 agent, pembrolizumab, and has been demonstrated as an important alternative to performing DART studies in NHPs<\/jats:p>","DOI":"10.1002\/bdrb.21176","type":"journal-article","created":{"date-parts":[[2016,4,10]],"date-time":"2016-04-10T17:49:00Z","timestamp":1460310540000},"page":"108-119","source":"Crossref","is-referenced-by-count":91,"title":["An Evaluation of the Impact of PD\u20101 Pathway Blockade on Reproductive Safety of Therapeutic PD\u20101 Inhibitors"],"prefix":"10.1002","volume":"107","author":[{"given":"Frederique M.","family":"Poulet","sequence":"first","affiliation":[{"name":"Merck Research Laboratories  Kenilworth New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayanthi J.","family":"Wolf","sequence":"additional","affiliation":[{"name":"Merck Research Laboratories  West Point Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danuta J.","family":"Herzyk","sequence":"additional","affiliation":[{"name":"Merck Research Laboratories  West Point Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph J.","family":"DeGeorge","sequence":"additional","affiliation":[{"name":"Merck Research Laboratories  West Point Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,4,7]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/8.5.765"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1037"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jri.2003.11.003"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/71641"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1472-6483(10)60577-9"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-006-0272-1"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.3.1257"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2004.09.004"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/5.6.541"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdrb.20216"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.2.945"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.8.5396"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/aji.12329"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1002031"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.3109\/10408444.2011.653487"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.27.2146"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.00.240"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3361"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI28214"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/5.3.234"},{"key":"e_1_2_8_22_1","unstructured":"FDA.Pharmacology review for OPDIVO (nivolumab). 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