Lung Cancer Has 1,283 Recruiting Trials and Three Arms Races

The Bottom Line

Keytruda loses patent exclusivity in December 2028. That deadline is pulling three separate competitive fronts into motion across non-small cell lung cancer (NSCLC), the most active pipeline on ClinicalTrials.gov: bispecific antibodies designed to replace Keytruda outright, KRAS inhibitors targeting the largest actionable mutation in lung cancer, and antibody-drug conjugates (ADCs) that may become the new backbone of first-line therapy.

The scale of the response: 1,283 NSCLC trials are recruiting right now, 153 of them in Phase 3, with over 135 companies competing. Seven new NSCLC drugs won FDA approval in 2025 alone, spanning ADCs, bispecifics, and targeted therapies (PMC, 2026). The one-drug-fits-all era of immunotherapy is ending. What replaces it is being decided now.

Those seven 2025 approvals spanned six different molecular targets, a sign of how fast NSCLC treatment is fragmenting (PMC, 2026; AACR, 2026):

In early 2026, zongertinib expanded to first-line HER2-mutated NSCLC (AACR, 2026). NSCLC is no longer one competitive market. It is splitting into biomarker-defined sub-markets, and competitive intelligence now means tracking six or more of them.

Who Has the Most Skin in the Game

AstraZeneca leads on volume: 29 recruiting trials, more than 50% ahead of Merck. But Merck leads on pivotal bets: 10 Phase 3 programs, the most of any sponsor. The gap between these two numbers tells you something about their strategies.

Notable absence from Phase 3: Pfizer has 15 recruiting trials but none in pivotal stages, suggesting a pipeline rebuild rather than a near-term competitive play.

Lead sponsor only. Recruiting trials as of April 19, 2026. Dashes indicate no Phase 3 trials returned under lead sponsor queries; sponsors may have Phase 3 programs as collaborators.

AstraZeneca Is Diversifying. Merck Is Doubling Down.

AstraZeneca is spreading bets across ADCs, bispecifics, and KRAS inhibitors. Merck is concentrating firepower on defending and extending Keytruda through combinations and a next-generation bispecific. Two different answers to the same question: what does post-Keytruda NSCLC look like?

The strategic read: AstraZeneca's breadth creates more entry points for licensing and co-development across mechanism classes. Merck's concentration creates a single large target. If you are building a pipeline that needs to differentiate against checkpoint inhibitors, AstraZeneca's bets tell you which alternatives the market is taking seriously.

Race 1: Three Bispecifics Want to Replace a $25B Drug

Keytruda (pembrolizumab) generates roughly 30% of Merck's revenue. Loss of exclusivity arrives December 2028 (Nasdaq, 2025). That deadline has created the defining competition in oncology: who becomes the next standard of care in first-line NSCLC?

The leading contenders are bispecific antibodies, engineered proteins that hit two targets simultaneously (typically PD-1 and VEGF). Three are in advanced development:

Race 2: Roche's Data Looks Better Than Amgen's. There's a Caveat.

KRAS G12C is the largest actionable mutation in lung cancer, found in roughly 13% of NSCLC patients. Two companies are fighting for this market, and the scoreboard looks lopsided until you read the fine print.

Sotorasib (Amgen) was first to market with a 41% response rate and 6.3-month median progression-free survival in second-line patients. Amgen is now pushing into first-line treatment: early combo data (sotorasib + chemo) showed a 65% response rate and 10.8-month median PFS (Amgen, 2023).

Divarasib (Roche/Genentech) posted a 59% response rate and 15.3-month median PFS in Phase 1. Numbers that look dramatically better. But these are cross-trial comparisons between a small Phase 1 study and larger Phase 3 data, which historically flatter early-stage results. Patient selection, trial design, and sample size all differ. The real answer comes from KRASCENDO-1, a head-to-head Phase 3 trial directly comparing divarasib against sotorasib and adagrasib, with results expected late 2027 (OncLive, 2025).

The class is also expanding. Elisrasib, a next-generation KRAS G12C inhibitor, showed promising activity at AACR 2026 (AACR, 2026). Amgen's AMG 410, a pan-KRAS inhibitor targeting multiple KRAS mutations beyond G12C, entered early development.

Race 3: ADCs Are Moving from Last Resort to First Choice

NSCLC treatment has evolved in waves. Chemotherapy dominated until checkpoint inhibitors (like Keytruda) reshaped first-line treatment a decade ago. Now ADCs (antibody-drug conjugates that deliver chemo payloads directly to tumor cells) are positioning to be the next shift. Three won FDA approval in 2025 alone:

• Dato-DXd (Datroway): targets TROP2 on tumor cells. Approved for EGFR-mutated NSCLC, now in 8 late-stage trials including TROPION-Lung08, which tests Dato-DXd + Keytruda vs. Keytruda alone in first-line patients (CancerNetwork, 2025).
• Telisotuzumab vedotin (Emrelis): first c-MET-targeted ADC in NSCLC (May 2025).
• Enhertu (T-DXd): HER2-targeted ADC already proven in breast cancer, now in Phase 3 for HER2-overexpressing NSCLC.

Daiichi Sankyo, which built the DXd payload platform behind both Dato-DXd and Enhertu, is preparing five ADC launches across indications in 2026 (Pharmaphorum, 2026). The trajectory is clear: ADCs are no longer last-line salvage options. They are being tested as first-line backbone agents.

Three Decisions That Will Reshape This Market

The next 12-18 months will resolve the biggest open questions in NSCLC:

• Does ivonescimab get a US approval? FDA decision expected Q4 2026. A yes validates the entire PD-1/VEGF bispecific class and puts Keytruda on the clock two years early. A no narrows the field to BNT327 and Merck's own MK-2010.
• Does divarasib confirm its edge over sotorasib in Phase 3? Early data favors Roche, but Phase 1 results have a well-known history of not holding up in larger trials. KRASCENDO-1 head-to-head results, due late 2027, will settle this. Until then, Amgen's first-line CodeBreaK 202 data could change the math.
• Can ADC + bispecific combinations replace chemotherapy in first-line? TROPION-Lung04 (Dato-DXd + rilvegostomig) and TROPION-Lung08 (Dato-DXd + Keytruda) are testing whether ADCs belong at the front of treatment, not the back. These are the most architecturally significant trials in NSCLC right now.