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 Drug

Sources

Last updated: May 2026

Essential reading

Shaywitz, David. "The Startling History Behind Merck's New Cancer Blockbuster." Forbes, Jul 26, 2017. The definitive Organon-era origin story.Loftus, Peter. "Why Merck Is Betting Big on One Cancer Drug." WSJ, Apr 15, 2018. Source for Perlmutter's "whatever other projects you're working on, you can stop now."Lowe, Derek. "The Keytruda Story." In the Pipeline.Graeber, Charles. The Breakthrough. Twelve, 2018.Primary interviews

Greg Carven, Michel Streuli, Roy Baynes — Approved podcast interviews (2026). Quotes attributed to these speakers come from these conversations unless otherwise noted.

Foundational science

Stutman. "Tumor development in athymic-nude mice." Science (1974). The flawed experiment that killed tumor immunology for two decades.Shankaran et al. "IFNγ and lymphocytes prevent primary tumour development." Nature (2001). Schreiber's cancer immunoediting paper.Leach, Krummel & Allison. "Antitumor immunity by CTLA-4 blockade." Science (1996). Allison's '100-to-zero' experiment.Ishida, Agata, Shibahara & Honjo. "Induced expression of PD-1." EMBO J (1992). Honjo discovers PD-1.Dong, Strome et al. "B7-H1 promotes T-cell apoptosis." Nat Med (2002). Lieping Chen's PD-L1 immune-evasion paper.Pivotal trials

Topalian et al. "Anti-PD-1 ...

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Data wydania: 14.05.2026, 15:00:00