Keytruda: How Merck's Pembrolizumab Became the Best-Selling Cancer Drug of All Time

Keytruda is Merck's $31 billion a year PD-1 inhibitor and the best-selling cancer drug of all time. In Episode 3 of Approved, Alex Kesin and Matthew Pech trace the development of pembrolizumab , featuring interviews the scientists who drove the program forward : co-inventors Gregory Carven and Michel Streuli, and former Merck oncology CMO Roy Baynes.Topics include preclinical PD1 / CTLA-4 checkpoint biology that brought industry attention to the target (Jim Allison's CTLA-4 work and Tasuku Honjo's PD-1 discovery); how pembro started as a failed rheumatoid arthritis antibody program at a Dutch subsidiary of a paint company; the two mega-mergers that nearly killed the program;  the biomarker enrichment trial design behind KEYNOTE-024 that let Merck break BMS's lead in lung cancer;  the 41-patient Johns Hopkins MSI-H trial behind the first tissue-agnostic FDA approval, and the Jimmy Carter melanoma case that brought pembrolizumab to the public conscious. The episode closes on what comes next for Merck: the 2028 patent cliff, the Keytruda QLEX subcutaneous launch, and efforts to find the next blockbuster checkpoint inhibitor, including Summit/Akeso's PD-1 / VEGF bispecific ivonescimab.This episode is presented by JLL. Featuring Grant Dettmer on biotech real estate strategy.CHAPTERS  00:00:00  —  Introduction: The Best-Selling Cancer Drug of All Time  00:02:15  —  Part One — A Century of Failed Cancer Immunotherapy  00:04:17  —  T Cells, CD28, and the Two-Signal Model of Immune Activation  00:06:25  —  Jim Allison's CTLA-4 Discovery and the Path to Yervoy  00:12:03  —  Tasuku Honjo Discovers PD-1: A Better Brake on T Cells  00:14:26  —  Lieping Chen and the PD-L1 Tumor Evasion Hypothesis  00:16:26  —  Part Two — Organon: The Dutch Paint-Company Subsidiary Behind Keytruda  00:19:48  —  How Michel Streuli Caught the Solid-Phase Screening Artifact  00:22:09  —  The Accidental Antagonist: From Rheumatoid Arthritis Drug to Cancer Drug  00:26:34  —  Sponsor: Grant Detmer (JLL) on Biotech Real Estate Strategy  00:30:01  —  Russian Nesting-Doll M&A: Schering-Plough Acquires Organon (2007)  00:31:43  —  The $41 Billion Merck–Schering-Plough Mega-Merger of 2009  00:34:58  —  Corporate Guerrilla Warfare: Four Scrappy Stunts That Saved Pembrolizumab  00:39:32  —  BioNovion's Spite-Company Bid to Buy Pembro Back  00:42:10  —  BMS at ASCO 2010: The Data Print That Revived Merck's PD-1 Program  00:45:55  —  Part Three — Roger Perlmutter Joins a Bleeding Merck (April 2013)  00:50:48  —  "Let Me Manage the Tigers": Ken Frazier Backs the All-In Bet on Pembrolizumab  00:55:22  —  Breakthrough Therapy Designation and Eric Rubin's Adaptive Trial Design  00:58:25  —  Keytruda's 2014 FDA Approval Erases BMS's Four-Year Lead  01:00:24  —  The Lung Cancer Battlefield and the PD-L1 Biomarker Bet  01:02:19  —  BMS vs. Merck: All-Comers vs. Biomarker-Enriched Trial Strategy  01:08:18  —  KEYNOTE-024 vs. CheckMate-026: The Trial That Decided the Category  01:12:03  —  Luis Diaz, MSI-H, and the Failed BMS Trial That Made Keytruda Tissue-Agnostic  01:17:18  —  KEYNOTE-189: Perlmutter's Bet on Combining Keytruda with Chemotherapy  01:19:21  —  Merck's Clinical Development Playbook: Basket Trials, Backwards March, External Collabs  01:25:29  —  Part Four — The IO Graveyard: TIGIT, CD47, IDO1, LAG-3 and Tens of Billions Incinerated  01:30:23  —  Why PD-1 Was the Only Checkpoint That Worked (Lieping Chen Revisited)  01:33:32  —  Part Five — Inside the Best-Selling Drug of All Time  01:37:03  —  "Build a Wall, High and Wide": Merck’s Commercial Strategy for Keytruda  01:43:44  —  Part Six — The Patent Cliff and Loss of Exclusivity in Pharma  01:45:35  —  Keytruda QLEX (Subcutaneous) and the Lifecycle Management Playbook  01:50:23  —  PD-1/VEGF Bispecifics: Ivonescimab, Summit Therapeutics, and the Next Threat  01:55:31  —  The Scorecard: Patient, Academic, and Financial Impact  02:01:19  —  Who Actually Profited: Merck vs. Organon vs. the Scientists Who Built the Drug  02:05:54  —  Epilogue: The Jimmy Carter DrugSourcesLast updated: May 2026Essential readingShaywitz, David. "The