A phase I dose-escalation study of MEDI-575, a PDGFRα monoclonal antibody, in adults with advanced solid tumors

PURPOSE: The purpose of the study was to evaluate safety and determine the maximum tolerated dose (MTD) of MEDI-575, a fully human monoclonal antibody that selectively binds to platelet-derived growth factor receptor-α (PDGFRα), in patients with advanced solid tumors. METHODS: This phase I multicenter, open-label, single-arm study enrolled adults in a 3 + 3 dose escalation design to receive MEDI-575 (3, 6, 9, 12, or 15 mg/kg) once weekly (QW) until toxicity or disease progression occurred. One 0.5-mg/kg dose was given before the first dose in the 3-mg/kg cohort to determine pharmacokinetics (PK) and pharmacodynamics under unsaturated conditions. After completion of dose escalation in the QW cohorts, patients were enrolled in two additional cohorts and received MEDI-575 25 or 35 mg/kg every 3 weeks (Q3W). Secondary measures included assessments of PK, immunogenicity, and antitumor activity. RESULTS: A total of 35 patients received MEDI-575 QW (n = 23) or Q3W (n = 12). Most treatment-related adverse events were grade 1 or 2 in severity across all dose levels, with fatigue (n = 12) and nausea (n = 8) being reported most frequently. With no reports of dose-limiting toxicities (DLTs), the MTD was not reached. MEDI-575 exhibited a nonlinear PK profile and increased plasma platelet-derived growth factor-AA levels in a dose-dependent manner with limited immunogenicity. Stable disease was reported as the best tumor response in 9 of 29 evaluable patients; however, no objective responses were reported. CONCLUSION: Administration of MEDI-575 QW or Q3W resulted in a favorable safety profile, including a lack of DLTs, but without evidence of antitumor activity in patients with refractory solid tumors

The Grizzly, November 24, 1992

Demas\u27s Furious Presentation • Possibility of AIDS Quilt at Ursinus • Lewis Receives the Muhlenberg Award • Share the Season • Clergy Assembly Held At U.C. • Senior Profile: Rick Naratil • Concert Band and Jazz Ensemble Perform Fall Concert • Messiah Tickets • Denis Leary\u27s No Cure For Cancer Breath of Fresh Air • Libo Speaks on Voyages to Freedom Exhibit • The Pointlessness of Political Correctness • Letters: Clark Responds to Christ on Campus ; Handicapped Accessibility: A Response From Someone Who Knows • Bears Basketball Buckles Under • Cross-Country Finishes Unbeaten Seasonhttps://digitalcommons.ursinus.edu/grizzlynews/1306/thumbnail.jp

The Grizzly, February 25, 1992

Airband 1992 Raises Over $1,200 for Charity • Flasher Hits Collegeville • Exchange Student to Speak • Good News For Bio Majors • Democratic Candidates • A Century of Main Street • Granite Column and Marble Bench • Wayne and Garth Big Hit in Wayne\u27s World • Jazz Quintet & Clifford Jordan to Perform • Movie Review: Dying Young • Americans Need to Lighten Up • Participation in Class: Intimidating or Not? • Men\u27s Basketball Stumbles to an End • Gymnasts Excel • Winter Olympics Comes to a Close • Lady Bears Win PAIAW Championship • Wrestlers Finish Strong Seasonhttps://digitalcommons.ursinus.edu/grizzlynews/1291/thumbnail.jp

The Grizzly, February 11, 1991

Fraternity Pledging Returns Again • Wachtel Explains the Poverty of Affluence • The Changing War • Peer Educators and Community Service • Alumni Visit the Ballet • Study Abroad Memorable • A Valentine History • Side Winders • Dance Marathon • Get Shorty • Triumph of the Spirit • Gymnasts Fare Well at Ithaca, Reach Team Goal • Track Women Place Third at PAIAW Championships • Hoopsters Rounding Out Season • Fro Scores Point, Swimmers Wash Out Widener • Wrestlers Excel • Letters: Bring Becker Back; Praise From Florida; Oh no, Mr. Bill!; Respect Yourself and Your Major • War: A Personal Experience on the Homefront • Who Wants the Persian Gulf War? • The Mephisto of Calculus • This Spill No Mistakehttps://digitalcommons.ursinus.edu/grizzlynews/1270/thumbnail.jp

The Grizzly, October 22, 1991

Alumni Return for Homecoming Celebration • Phi Beta Kappa Charter Approved for Ursinus • Thomas Confirmed to Supreme Court • Gibson to Speak at Ursinus • GALA Seeks Recognition • U.S.G.A. Minutes • GALA Comes Out • Modern Medical Imaging • The Vision of Science Through Art • Beware of Bad Moods • Woman Fixing Her Hair? • Critics\u27 Corner: The Fisher King; Sleeping With the Enemy • Giggles Night Club Comedians • Letters: In Defense of Harley; Harassment Response; An Appeal for the Trees • Apples and Oranges • Dining Turf • Bears Blank the Bullets in Homecoming Game • Cross Country Runs to Victory • Field Hockey Strikes Back, Raises Record to 5-5-2 • Volleyball Spikes Cabrini • Lady Bears Cruise to 1st Place • Winds Fill Ursinus\u27 Sails • Soccer Bounces Back with Three Straight Winshttps://digitalcommons.ursinus.edu/grizzlynews/1280/thumbnail.jp

The Grizzly, October 8, 1991

1991 Parents\u27 Day a Great Success • Homecoming Festivities Planned • Is the Soviet Union Dead? • Teacher Appreciation Dinner a Success • Tortorelli at NASA • What About Recycled Paper? • Movie Review: Misery • Jane Powell Returns • Saffire: Uppity Blues Women • The Aggressive Couple • Homecoming Queen Nominees • Ethnic Degradation • Unsafe City • Appreciate Today • Construction Blues • Letter: Come On, Harley! • Bears Maul Swarthmore • Lady Bears Run to Victory • Volleyball Gets Spiked • Field Hockey Drives for Victory • Too Early to Tell? No Way • Cross Country Takes 2nd • Soccer Team Struggles Among Tough Competition • Flag Football Follieshttps://digitalcommons.ursinus.edu/grizzlynews/1279/thumbnail.jp

The Grizzly, October 16, 1990

Olin Walkway Changes the Face of Ursinus • Congressional Candidate Lewis Du Pont Smith Spurs Debate • The Minority Student Union: A Step Toward Diversity • USEAC Conference Bolsters Environmental Activism • Father Changes • Reflecting on Rosen • New Hang-out • The Replacements • Upcoming Berman • Cross Country Runs On • Soccer Wins Two • Netters Upset • Hockey Splits • Grubb Predicts Again • Football Refuses To Give Up • Letters: Complain, but Don\u27t Steal; Positive Pledging; Wismer Food: Quick Service and Healthy Variety • A Contradiction in American Beliefs • This is America? • A Spectacular Devicehttps://digitalcommons.ursinus.edu/grizzlynews/1261/thumbnail.jp

The Grizzly, October 29, 1991

Charles Gibson Speaks to Crowd • Blood Drive a Success • Pledging Ends • Clergy Assembly for Professional Development on Campus Next Week • Hood Speaks on Morals at Tri-Lambda Meeting • The Environmental Corner • The Experience of a Lifetime • Environmental Chemistry and its Price • Trimming the Fat • Snoopy • Berman Opens Two New Exhibits • Dating Game a Success • Carlin Captivates at Valley Forge • ProTheatre Presents ... The Crucible • Haunted Hayride • Silence of the Lambs • Thought Organization • America: A Nation of Sissies • Letters: Clarification of GALA; Put Your Mouth Where Your Money Is • Bears Have a Devil of a Time with FDU • Lady Bears Finish 4th at PAIAW • Field Hockey Sticks it to St. Joe\u27s • Lady \u27Mers Swim to Victory at Ship Relays • Men\u27s Lacrosse Defeats St. Joseph\u27s • Flag Football • Men Swimmers Start Season • Cross Country Runs Widener Ragged • Golf Scores • Farleigh-Dickinson and Haverford Bounce by Ursinushttps://digitalcommons.ursinus.edu/grizzlynews/1281/thumbnail.jp

The Grizzly, September 24, 1991

Ursinus Day Academic Convocation Changes Face • Alcohol Policy Enforcement Tightens • Freshman Class Elections Held • Dr. Hall Honored • U.S.G.A. Minutes • Student Response Team Regroups • Demas Presents... Barry Hixson • Sororities Begin Formal Rushing • Finally! Student Center Opens • Golf Gets New Head Coach • Paul Harryn Launches Berman Season • DeLuca Hypnotizes Audience • Movie Reviews: Pacific Heights; New Jack City; Hot Shots • Volleyball Nets a Win • Lady Bears Stick It to Opponents • Nick\u27s NFL Notes • Bears Harass Hoyas in Opener • Soccer Kicks Off Season with Win • U.C. Tavern? • Questions of Freedom • Defense of History • Life Science Building Upgraded to State-Of-The-Art Facility • Pre-med Committee Evaluation Meeting • Medicine in The Gulf Warhttps://digitalcommons.ursinus.edu/grizzlynews/1277/thumbnail.jp