The Cancer Drugmakers Pulling Ahead—and What They’re Building Next

Oncology has always been pharmaceutical development’s most contested and commercially consequential arena. What makes the current moment unusual is the simultaneity of it. A dense run of late-phase readouts across pancreatic cancer, lung cancer, breast cancer, lymphoma, liver cancer, brain metastases, and colorectal cancer has landed within the same season — each result shifting competitive territory that, in some cases, had been static for decades. Many of the most influential findings were presented at ASCO 2026, where companies used the world’s largest oncology meeting to showcase data that could reshape both clinical practice and competitive positioning.

Collectively, the data pointed to three themes that surfaced repeatedly across company presentations: the rise of antibody-drug conjugates (ADCs), the growing importance of biomarker-driven patient selection, and a strategic shift toward treating cancer earlier in the adjuvant and perioperative setting. The companies positioned to benefit are not simply those with the most approved drugs. They are those that correctly identified the next molecular target, secured the right partnership, and moved into earlier treatment lines before rivals could.

Revolution Medicines: The Biotech That Just Changed Pancreatic Cancer

Until this spring, Revolution Medicines (Nasdaq: RVMD) was a well-regarded late-stage oncology biotech. Now it is the most talked-about company in the field. The reason is a single clinical trial result that reordered expectations for one of medicine’s most intractable diseases.

The phase 3 RASolute 302 trial (NCT06625320) tested daraxonrasib — an oral, once-daily RAS(ON) multi-selective inhibitor — against standard chemotherapy in 501 patients with previously treated metastatic pancreatic ductal adenocarcinoma. The results, simultaneously published in the New England Journal of Medicine, showed a median overall survival of 13.2 versus 6.7 months and a 60% reduction in mortality risk (HR 0.40; p < 0.0001). Progression-free survival improved from 3.5 to 7.3 months. Response rates were 33.2% versus 11.8%. Serious adverse events ran in daraxonrasib’s favor — 43.6% versus 57.5% with chemotherapy.

That combination — a near-doubling of survival with a lower toxicity burden — is unprecedented in any randomized second-line PDAC trial. The FDA has already granted Breakthrough Therapy Designation for daraxonrasib in previously treated PDAC, and the company has announced plans to file a New Drug Application under a Commissioner’s National Priority Voucher. Expanded access is now authorized by the FDA for eligible patients who cannot wait.

But the PDAC second-line approval is only the first piece of what Revolution Medicines is building. The company currently has three additional registrational programs running:

• RASolute 303: A phase 3 trial evaluating daraxonrasib as monotherapy and in combination with chemotherapy (gemcitabine/nab-paclitaxel) in first-line metastatic PDAC. Treatment of patients began in 2026.
• RASolute 304: Adjuvant PDAC, testing daraxonrasib in the post-surgical setting where residual disease is the primary enemy.
• RASolve 301: A global phase 3 trial of daraxonrasib monotherapy in previously treated non-small cell lung cancer, with enrollment expected to substantially complete in 2026.
• Zoldonrasib (NSCLC): A separate RAS G12D-selective inhibitor with FDA Breakthrough Therapy Designation in lung cancer, with a Phase 3 doublet combination trial (RASolute 309, zoldonrasib plus daraxonrasib) planned for the second half of 2026.

Revolution Medicines has also raised $2.2 billion in gross proceeds, including a $2 billion funding agreement with Royalty Pharma, giving the company the runway to execute this pipeline without capital constraints. The company’s CEO has described the daraxonrasib results as the beginning of pancreatic cancer’s transition “from intractable to manageable.” Based on what has been published, that framing does not look like overclaiming.

Bristol Myers Squibb and SystImmune: Building an ADC Franchise Across Multiple Cancers

Bristol Myers Squibb (NYSE: BMY) arrived with the largest data package of any company this season — more than 60 disclosures and 19 oral presentations — and the headline result belongs to a partnership that is quietly reshaping the antibody-drug conjugate landscape.

The asset is izalontamab brengitecan (iza-bren), a potentially first-in-class EGFRxHER3 bispecific ADC developed by SystImmune and licensed outside China to BMS. What makes iza-bren strategically exceptional is its breadth: it has now delivered positive phase 3 results in three different cancer types across three different trials.

• Triple-negative breast cancer (PANKU-Breast02, NCT06382142): Iza-bren improved both PFS and OS versus physician’s choice chemotherapy in previously treated TNBC patients. Median OS reached 15.9 versus 12.5 months, a 40% reduction in mortality risk. This was the first phase 3 bispecific ADC to achieve dual primary endpoint improvement in TNBC.
• Esophageal squamous cell carcinoma (PANKU-Esophagus01): Similarly positive results on both PFS and OS endpoints at the same data cut.
• Nasopharyngeal carcinoma: Positive phase 3 results presented at ESMO 2025 established iza-bren in a third tumor type before this year’s readouts.

A drug that succeeds across three phase 3 trials in three cancer types is no longer a promising asset. It is a franchise. BMS and SystImmune have already disclosed plans to expand iza-bren into extensive-stage small cell lung cancer and additional solid tumors, and regulatory submissions for TNBC and ESCC are expected to follow the current data.

On the hematology side, BMS is also advancing mezigdomide, a next-generation CELMoD (cereblon E3 ligase modulator) from its targeted protein degradation platform, in relapsed/refractory multiple myeloma via the late-breaking phase 3 SUCCESSOR-2 trial. The CELMoD franchise represents BMS’s central strategic play for the post-Revlimid era of myeloma treatment.

Merck and Moderna: Five Years of Vaccine Data That Are Changing the Conversation

Merck (NYSE: MRK) brought more than 100 abstracts spanning 25-plus cancer types — the broadest data package of any company. Keytruda remains the world’s best-selling cancer drug. But the most strategically significant result is not Keytruda alone: it is what Keytruda does when paired with a personalized mRNA cancer vaccine.

Five-year follow-up data from KEYNOTE-942 (NCT03897881), evaluating intismeran autogene (mRNA-4157, co-developed with Moderna) plus pembrolizumab in resected high-risk melanoma, show the risk reduction has not faded. At five years, the combination maintained a 49% reduction in recurrence or death versus pembrolizumab alone (HR 0.51). Five-year overall survival was 92.2% in the combination arm versus 71.3% with pembrolizumab alone. Distance metastasis-free survival improved by 59%.

What the five-year timepoint establishes is durability — and that matters more than the number itself. The 49% risk reduction at five years is identical to what was reported at three years, suggesting the vaccine is reprogramming long-term immune surveillance rather than producing a transient effect. The FDA has previously evaluated the phase 2b data and deemed them insufficient for accelerated approval; INTerpath-001, the confirmatory phase 3 trial in adjuvant melanoma, is fully enrolled with interim data potentially expected later in 2026.

The broader pipeline is substantial. Merck and Moderna currently have nine phase 2 and phase 3 trials underway for intismeran autogene, spanning melanoma, non-small cell lung cancer, bladder cancer, and renal cell carcinoma. Two NSCLC phase 3 studies are enrolling. Phase 2 studies in muscle-invasive and non-muscle-invasive bladder cancer are underway. A phase 3 program in early-stage NSCLC (INTerpath-014) has recently initiated. The NSCLC lung readouts are unlikely before 2030, but the platform’s eventual reach — if it holds in confirmatory melanoma and extends to lung — would be transformative.

Merck also presented long-term KEYNOTE-522 data confirming sustained survival benefit for pembrolizumab plus chemotherapy in high-risk early-stage TNBC, and featured ASCENT-04/KEYNOTE-D19 (pembrolizumab plus sacituzumab govitecan in metastatic TNBC) in its press program — reinforcing that Keytruda’s role is expanding not just in melanoma but across the breast cancer treatment landscape.

AstraZeneca: The ADC Leader With a Liver Cancer Win — and a TROP2 Competition Heating Up

AstraZeneca (Nasdaq/LSE: AZN) arrived with ten approved medicines and 13 pipeline assets across its oncology portfolio. Its headline result was EMERALD-3 — a phase 3 trial demonstrating that adding durvalumab (Imfinzi) plus tremelimumab (Imjudo) to transarterial chemoembolization (TACE) in unresectable hepatocellular carcinoma improved both PFS and OS versus TACE alone, a procedure that had been the locoregional standard for two decades. The result establishes systemic dual immunotherapy plus locoregional therapy as a viable new standard in liver cancer.

AstraZeneca’s deeper structural advantage, though, sits in its ADC franchise via the Daiichi Sankyo partnership. Enhertu (trastuzumab deruxtecan) continues to expand across HER2-expressing tumor types, with the phase 3 DESTINY-Breast09 trial evaluating Enhertu plus pertuzumab in first-line HER2-positive breast cancer. Datroway (datopotamab deruxtecan) — the TROP2-directed ADC — received FDA approval in May 2026 as the first TROP2-directed ADC for first-line metastatic TNBC in patients who are not immunotherapy candidates, with an unprecedented median OS of approximately two years in that setting. The company now has more than 20 active trials for Datroway across NSCLC, TNBC, and urothelial cancer, including eight phase 3 studies in lung cancer alone.

The competitive complication for AstraZeneca in lung cancer is real. Phase 2 results for sacituzumab tirumotecan (sac-TMT) — a TROP2-directed ADC being developed by Merck and Chinese partner Kelun — demonstrated strong first-line efficacy in NSCLC, tightening the TROP2 competitive picture in the indication where Datroway is most exposed. AstraZeneca’s DXd platform advantage is its payload technology and trial breadth; the coming years will determine whether that depth is sufficient to hold ground as rival TROP2 agents mature.

Pfizer: Defending Established Drugs While a Next-Generation Pipeline Takes Shape

Pfizer (NYSE: PFE) presented more than 40 abstracts, running two parallel stories: defending existing franchises with long-term data, and building a next-generation pipeline that is just entering phase 3. The combination is strategically coherent, even if neither thread individually generates the immediate impact of a daraxonrasib or an iza-bren.

On the established side, long-term phase 3 CROWN data extended lorlatinib’s lead position in ALK-positive metastatic NSCLC. BRAFTOVI (encorafenib) plus cetuximab in BRAF V600E-mutant colorectal cancer featured across first-line and post-treatment settings, capitalizing on the FDA traditional approval in the BREAKWATER indication. TALZENNA plus XTANDI data addressed metastatic castration-sensitive prostate cancer.

The forward-looking pipeline centers on three assets, all moving into or through phase 3:

• Sigvotatug vedotin (SV): A novel integrin β6-directed ADC in combination with pembrolizumab, supported by phase 1 data in NSCLC. Two active phase 3 studies: SigVie-003 evaluating SV plus pembrolizumab in first-line NSCLC, and SigVie-002 evaluating SV monotherapy in previously treated advanced NSCLC.
• PF-08634404 (PF’4404): A bispecific antibody targeting both PD-1 and VEGF — a mechanistic bet that immune checkpoint blockade plus angiogenesis inhibition can function in a single molecule. Phase 2 monotherapy data in first-line PD-L1-expressing NSCLC have been presented; phase 3 studies are active in first-line NSCLC (Symbiotic-Lung-01) and first-line metastatic colorectal cancer (Symbiotic-GI-03).
• Atirmociclib: A highly selective CDK4 inhibitor, distinct from first-generation CDK4/6 inhibitors in its selectivity profile. Phase 2 neoadjuvant data in HR-positive, HER2-negative breast cancer have been presented; the FourLight-3 phase 3 study in first-line HR+/HER2-negative metastatic breast cancer is enrolling.

The common thread across all three is a first-line positioning ambition. If any two of these three assets deliver in their phase 3 programs, Pfizer’s next-generation oncology story changes materially.

Eli Lilly: A Precise Win in Lung Cancer, and a Platform Ready to Expand

Eli Lilly’s oncology story this season is narrower than BMS or Merck’s but no less significant within its lane. The phase 3 LIBRETTO-432 trial (NCT04819100) tested adjuvant selpercatinib (Retevmo) following resection in patients with stage IB–IIIA RET fusion-positive non-small cell lung cancer. In 109 patients with stage II–IIIA disease, selpercatinib reduced recurrence, progression, or death risk by 83% versus placebo (HR 0.172; P = 0.0003). Two-year event-free survival was 91.5% versus 61.1% with placebo.

This is a commercially significant label expansion. Selpercatinib moves from the metastatic setting — where it was already approved — into curative-intent post-surgical care for a patient population that is, by definition, healthier and likelier to benefit from treatment. RET fusions affect roughly 1–2% of NSCLC patients, but the adjuvant setting represents a distinct and underserved population that prior data had not addressed. The result joins adjuvant osimertinib (ADAURA) and adjuvant alectinib (ALINA) in confirming that the adjuvant targeted therapy model extends beyond EGFR and ALK to RET-driven tumors.

Regulatory submission for adjuvant selpercatinib in RET-positive NSCLC is expected to follow. Selpercatinib expansion data in RET-altered thyroid cancer and other solid tumors continue to mature, and Lilly’s capital position — substantially strengthened by the tirzepatide-driven metabolic portfolio — gives the company the resources to accelerate its oncology pipeline build-out.

Three Forces Shaping Who May Lead in Oncology Over the Next Five Years

Across every company in this read, three structural patterns dominate the current moment and will define oncology development through at least 2030.

ADCs Are No Longer a Niche Technology: Iza-bren succeeding in three cancer types, AstraZeneca’s Enhertu and Datroway franchises expanding, Pfizer building sigvotatug vedotin toward phase 3, Merck advancing sac-TMT in lung cancer — every major company is either competing in antibody-drug conjugates or building toward it. The technology’s ability to deliver cytotoxic payloads directly to tumor cells while limiting systemic toxicity, and the emergence of bispecific ADCs targeting two surface proteins simultaneously, is pushing ADCs into earlier treatment lines across almost every solid tumor type.

The question is no longer whether ADCs work. It is which target combinations and payloads produce the most favorable efficacy-toxicity profiles, and which companies secured the best targets and manufacturing capabilities before the field became crowded.

Biomarker Testing Is Now Infrastructure, Not Aspiration: The trials that produced the most significant results this season — RAS mutation testing for daraxonrasib, RET fusion testing for selpercatinib, BRAF V600E for BREAKWATER, HER2 expression for Enhertu — all required molecular patient selection as a precondition for entry. Precision oncology has moved from aspiration to operational baseline. The companies best positioned are those with the companion diagnostics, biomarker testing partnerships, and patient identification infrastructure to ensure the right patients are found and enrolled.

Adjuvant and Perioperative Settings Are the New Commercial Frontier: LIBRETTO-432 in lung cancer, the vaccine program in melanoma, adjuvant osimertinib and alectinib in NSCLC, and daraxonrasib’s expanding PDAC adjuvant program all point in the same direction: the field is intervening earlier, in the post-surgical period before residual disease becomes metastatic disease. The commercial logic is straightforward. A drug that prevents recurrence in a patient with resectable disease reaches a larger, healthier, and better-tolerating population than the metastatic setting that historically defined most oncology drug markets. The companies moving into these settings now are positioning for the revenue cycles of the next decade.

Author

Bernice Lottering

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