NSCLC Newsletter - April 2026

NSCLCApril 2026

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Non-Small Cell Lung Cancer — Monthly Compass

Apr 01–30, 2026 • Priority Updates • 3–5 minute read

A curated, practice-minded digest of what moved in non-small cell lung cancer this month — regulatory signals, clinical development, and the most practice-relevant publications.

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Key Highlights

Practice-Changing Updates
- The phase III RATIONALE-315 final analysis demonstrated that perioperative tislelizumab combined with neoadjuvant chemotherapy significantly improved overall and event-free survival versus chemotherapy alone in resectable stage II–IIIA NSCLC, supporting its adoption as a standard-of-care option.
- The phase 3 LungTIME-C01 trial showed that administering immunochemotherapy before 15:00 h significantly improved progression-free and overall survival compared with later administration in treatment-naïve advanced NSCLC, indicating a simple, cost-free scheduling intervention to enhance efficacy.
Important Drug Publication Updates
- The MARIPOSA analysis reported that first-line amivantamab plus lazertinib significantly reduced the emergence of MET amplifications and secondary EGFR mutations compared with osimertinib, translating into substantially prolonged second-line progression-free survival.
- Patient-reported outcomes from the phase III LAURA study confirmed that osimertinib maintains health-related quality of life after definitive chemoradiotherapy in unresectable stage III EGFR-mutated NSCLC, reinforcing integration of this regimen alongside its significant progression-free survival benefit and manageable safety.
Key Clinical Development Updates
- Nuvalent submitted a U.S. NDA for neladalkib (NVL‑655) in TKI‑pretreated ALK‑positive NSCLC and received FDA acceptance of the NDA for zidesamtinib (NVL‑520) in ROS1‑positive NSCLC with a PDUFA target action date of September 18, 2026.
- FDA accepted the NDA for zipalertinib (CLN‑081/TAS6417) for post‑platinum EGFR exon 20 insertion‑mutated NSCLC with a PDUFA date of February 27, 2027, while MAIA’s phase 3 THIO‑104 in third‑line NSCLC is fully funded with Fast Track designation and an interim readout next year to inform potential early approval discussions, and recent milestones included RMAT for KB707 and BLA acceptance for ivonescimab plus chemotherapy with a PDUFA goal of November 14, 2026.
Important Clinical Trial Publications
- Long‑term follow‑up confirmed that taletrectinib delivers high, durable response rates with robust intracranial activity and a median progression‑free survival exceeding four years in TKI‑naïve ROS1‑positive NSCLC, while the third‑generation ALK inhibitor deulorlatinib achieved a 43.7% objective response rate with strong G1202R activity after second‑generation ALK inhibitors.
- The phase 3 SKYSCRAPER‑06 trial was terminated early after failing to meet its primary endpoints, as adding tiragolumab to atezolizumab and chemotherapy did not improve progression‑free or overall survival versus pembrolizumab plus chemotherapy in first‑line advanced nonsquamous NSCLC.
Key Conference Updates
- AACR 2026 highlighted durable responses from the KRAS G12D inhibitor zoldonrasib, CNS‑optimized ROS1 inhibition with zidesamtinib including G2032R and intracranial activity, rapid ADC diversification across 5T4, integrin β6, and EGFR/HER3 with novel payloads, perioperative adenosine‑axis triplets adding anti‑CD39 (IPH5201) to durvalumab plus chemotherapy, and AI pathomics that outperformed PD‑L1 for predicting immunotherapy outcomes.
Emerging Themes & Macro-Trends
- Strategic priorities emphasized CNS‑active, resistance‑addressing TKIs, diversification into non‑Topo‑I and bispecific ADC platforms, and integration of AI pathomics to enrich immunotherapy trials and real‑world decision support.
- Regulatory trajectories indicate that potential approval of zidesamtinib could recalibrate ROS1 testing and sequencing while perioperative anti‑CD39 combinations may prompt alignment of pCR, MPR, and EFS endpoints.

FDA Approvals/Withdrawals

There are no press releases between 2026-04-01 and 2026-04-30 about non-small cell lung cancer.

Clinical Development Regulatory Updates

Nuvalent announced it submitted a U.S. NDA for neladalkib (NVL-655), a brain-penetrant ALK-selective TKI, for TKI pre-treated advanced ALK-positive NSCLC based on data from the registrational ALKOVE-1 trial; the company also noted FDA Breakthrough Therapy and Orphan Drug designations for the program. The filing advances neladalkib into formal FDA review for patients previously treated with ALK TKIs. (investors.nuvalent.com) ¹ (read more)
During AACR 2026 coverage, Nuvalent reported that the FDA accepted its NDA for zidesamtinib (NVL-520) for ROS1-positive NSCLC after at least one prior ROS1 TKI and assigned a PDUFA target action date of September 18, 2026. The update accompanied new clinical and preclinical data from the ARROS-1 program. (ca.marketscreener.com) ² (read more)
Taiho Oncology, Taiho Pharmaceutical, and Cullinan Therapeutics announced FDA acceptance of the NDA for zipalertinib (CLN-081/TAS6417) to treat adult patients with locally advanced or metastatic EGFR exon 20 insertion–mutated NSCLC after platinum chemotherapy (with or without prior amivantamab); the FDA set a PDUFA target action date of February 27, 2027. The application is supported by Phase 2b REZILIENT1 data showing clinically meaningful and durable responses. (biospace.com) ³ (read more)
MAIA Biotechnology disclosed its Phase 3 THIO-104 trial in third-line NSCLC is fully funded and reiterated that lead candidate ateganosine has FDA Fast Track designation in this setting. The company said interim data expected next year may support FDA discussions about potential early full approval. (sec.gov) ⁴ (read more)
An April 16 NSCLC pipeline update highlighted recent U.S. regulatory milestones including FDA RMAT designation (February 2026) for Krystal Biotech’s KB707 in advanced/metastatic NSCLC and FDA acceptance (January/February 2026) of Summit Therapeutics’ BLA for ivonescimab plus chemotherapy in post‑TKI EGFR‑mutated NSCLC, with a PDUFA goal date of November 14, 2026. The report compiles ongoing FDA review timelines and expedited pathways relevant to multiple NSCLC programs. (globenewswire.com) ⁵ (read more)

Major Conference Updates

Conference Information

American Association for Cancer Research (AACR) Annual Meeting 2026; San Diego Convention Center, San Diego, California; April 17–22, 2026. (read more)
Overall sentiment: NSCLC updates highlighted next‑gen precision inhibitors (KRAS G12D/G12C, ROS1), rapid ADC diversification, and perioperative adenosine‑axis combinations, with emerging AI biomarkers to optimize immunotherapy selection. (read more)

Theme 1: Next‑Gen Precision Inhibitors (KRAS and ROS1)
- Significance: Momentum shifted beyond KRAS G12C toward KRAS G12D (zoldonrasib) while next‑gen G12C (elisrasib) and a CNS‑optimized ROS1 inhibitor (zidesamtinib) advance, expanding targeted options post‑chemo/IO and after earlier TKIs. (read more)
- Mechanism insights / clinical impact: Zoldonrasib, a G12D‑selective RAS(ON) inhibitor, showed durable responses with favorable safety; elisrasib achieved high disease control including after prior G12C therapy; zidesamtinib demonstrated activity in ROS1 G2032R and intracranial responses with differentiated brain penetrance. (read more)
- Patient populations affected: KRAS G12D–mutated and KRAS G12C–mutated advanced NSCLC; ROS1‑positive NSCLC including CNS‑met and TKI‑pretreated subsets. (read more)
Theme 2: ADC Diversification and Payload Innovation
- Significance: Multiple AACR presentations signaled a broad ADC push in NSCLC across new targets (5T4, ITGB6, EGFR/HER3) and novel payloads (RNA splicing modulators) to overcome heterogeneity and Topo‑I resistance. (read more)
- Mechanism insights / clinical impact: JK06 (5T4‑MMAE) showed encouraging ORR with predominantly low‑grade AEs; STRO‑006 (integrin β6, exatecan) and CS5007 (EGFR/HER3 bispecific ADC, exatecan) demonstrated potent preclinical activity; AKTX‑101’s spliceosome‑modulating payload (PH1) exhibited differentiated cytotoxicity and IO‑combination potential. (read more)
- Patient populations affected: Advanced NSCLC, including squamous and EGFR‑mutant subsets; broader TROP2‑expressing tumors with NSCLC cohorts anticipated. (read more)
Theme 3: Perioperative Adenosine‑Axis Triplets in Resectable Disease
- Significance: Early‑setting combinations added an anti‑CD39 antibody (IPH5201) to durvalumab + platinum chemotherapy (MATISSE, phase 2), aiming to deepen pCR/MPR and sustain EFS in resectable NSCLC. (read more)
- Mechanism insights / clinical impact: CD39 blockade counters adenosine‑mediated immunosuppression, potentially enhancing PD‑L1 and chemotherapy effects in the perioperative window; interim data selection for AACR plenary underscores clinical interest. (read more)
- Patient populations affected: Resectable, treatment‑naïve NSCLC candidates for neoadjuvant chemo‑IO plus adjuvant strategies. (read more)
Theme 4: AI‑Driven Immunotherapy Selection
- Significance: Pathomics‑based “Path‑IO” outperformed PD‑L1 in stratifying outcomes among ICI‑treated metastatic NSCLC, foreshadowing workflow‑ready companion tools. (read more)
- Mechanism insights / clinical impact: Deep‑learning analysis of routine H&E slides integrates TME “niches” with clinico‑radiomics to predict OS/PFS and refine IO benefit estimates across international cohorts and a randomized dataset. (read more)
- Patient populations affected: Metastatic NSCLC receiving checkpoint inhibitors across health‑system settings; potential global applicability pending prospective validation. (read more)
Significance
- Expected clinical or translational readouts: Zidesamtinib NDA under FDA review (PDUFA September 18, 2026); STRO‑004 phase 1 initial results mid‑2026; CS5007 IND initiation planned 1H26; AKTX‑101 IND in 4Q26. (read more)
- Regulatory or policy implications: If approved, zidesamtinib could recalibrate ROS1 testing/sequence post‑repotrectinib/taletrectinib; perioperative anti‑CD39 combinations may prompt endpoint alignment (pCR/MPR/EFS). (read more)
- Potential shifts in standard of care: Positive KRAS G12D and next‑gen G12C signals support targeted options beyond current G12C agents; perioperative adenosine‑axis triplets could intensify cure‑aimed regimens. (read more)
- Strategic implications: Prioritize CNS‑active TKIs and resistance‑addressing labels; invest in non‑Topo‑I and bispecific ADC platforms; integrate AI pathomics into trial enrichment and real‑world IO decision support. (read more)

Efficacy of selpercatinib as a first-line treatment for RET-fusion positive non-small-cell lung cancer: a novel two-stage Bayesian network meta-analysis. A novel two-stage Bayesian network meta-analysis incorporating single-arm trial data demonstrates that first-line selpercatinib significantly improves progression-free and overall survival compared to pemetrexed plus platinum-based chemotherapy in RET-fusion positive non-small-cell lung cancer. This methodological approach provides a robust framework for health technology assessments, offering payers greater confidence in evaluating single-arm trial data against multiple relevant comparators. ()

📋 NCT02578680

📋 NCT03157128

Patient-reported outcomes from the LAURA study: osimertinib in patients with unresectable stage III EGFR-mutated non-small cell lung cancer after definitive chemoradiotherapy. Patient-reported outcomes from the phase III LAURA study confirm that osimertinib maintains health-related quality of life and functioning in patients with unresectable stage III EGFR-mutated NSCLC following definitive chemoradiotherapy. Coupled with its significant progression-free survival benefit and manageable safety profile, these findings strongly support the integration of osimertinib into this clinical setting. ()

📋 NCT03521154

Treatment Patterns and Clinical Outcomes in Unresectable Stage III EGFR-Mutated Non-Small Cell Lung Cancer in China. A real-world retrospective analysis of Chinese patients with unresectable stage III EGFR-mutated NSCLC reveals that while first-generation EGFR-TKIs following chemoradiotherapy offer numerically longer progression-free survival compared to chemoradiotherapy alone, significant unmet needs remain. These findings underscore the necessity for broader adoption of more efficacious therapies, such as third-generation EGFR-TKIs, to further prolong survival in this population. ()

📋 NCT03521154

📋 NCT04194944

Long-Term Impact of First-Line Amivantamab Plus Lazertinib Versus Osimertinib on Mechanisms of Acquired Resistance in MARIPOSA: A Brief Report. Analysis of the MARIPOSA trial reveals that first-line amivantamab plus lazertinib significantly reduces the emergence of common acquired resistance mechanisms, such as MET amplifications and secondary EGFR mutations, compared to osimertinib in EGFR-mutated advanced NSCLC. This alteration in underlying tumor biology translates to a substantially prolonged second-line progression-free survival, highlighting the long-term strategic advantage of this combination therapy. ()

📋 NCT04487080

Overall survival for amivantamab plus lazertinib versus osimertinib as first-line treatment in Asian participants with EGFR-mutant advanced NSCLC: A MARIPOSA subset analysis. A subset analysis of the MARIPOSA trial demonstrates that first-line amivantamab plus lazertinib significantly prolongs overall survival compared to osimertinib in Asian patients with EGFR-mutated advanced NSCLC. This clinically meaningful survival benefit, coupled with a consistent safety profile, establishes amivantamab plus lazertinib as a highly effective therapeutic option for this specific demographic. ()

📋 NCT04487080

FDA Approval Summary: Tarlatamab for the Treatment of Extensive-Stage Small Cell Lung Cancer. The FDA has granted accelerated approval to tarlatamab for adult patients with extensive-stage small cell lung cancer progressing after platinum-based chemotherapy, based on an impressive 40% overall response rate and a median duration of response of 9.7 months in the DeLLphi-301 trial. Clinicians must remain vigilant regarding the boxed warnings for serious cytokine release syndrome and neurologic toxicity, necessitating careful patient monitoring and management strategies. ()

📋 NCT05060016

New Publications Related to Drugs in Clinical Trial Development

Decoding B-cell Signatures of Complete Pathologic Response to Perioperative Chemoimmunotherapy in Non-Small Cell Lung Cancer. Multiomic analysis of patients with resectable non-small cell lung cancer receiving perioperative chemoimmunotherapy revealed that a complete pathologic response is associated with a preexisting, more clonal B-cell receptor repertoire that matures during treatment. These findings highlight the critical role of B-cell responses and tertiary lymphoid structures in mediating efficacy, suggesting B-cell receptor metrics could serve as promising predictive biomarkers. ()

📋 NCT03838159

Long-Term Efficacy and Safety of Taletrectinib in Patients With ROS1+ Non-Small Cell Lung Cancer: Results From the Phase II TRUST-I Study. Long-term follow-up from the phase II TRUST-I study confirms that the next-generation ROS1 inhibitor taletrectinib delivers high, durable response rates and robust intracranial activity in both TKI-naïve and crizotinib-pretreated patients with advanced ROS1+ non-small cell lung cancer. The sustained efficacy, including a median progression-free survival exceeding 4 years in TKI-naïve patients, alongside a manageable safety profile, supports its use as a highly effective targeted therapy. ()

📋 NCT04395677

Durvalumab Plus Chemotherapy in Patients With EGFR-Mutated Advanced NSCLC Whose Disease Progressed on First-Line Osimertinib: ORCHARD. In the ORCHARD platform study, the combination of durvalumab plus platinum-based chemotherapy demonstrated limited clinical benefit in patients with EGFR-mutated advanced non-small cell lung cancer who progressed on first-line osimertinib. Despite being well tolerated, the low objective response rate of 16% indicates that this combination does not warrant further evaluation in this specific post-osimertinib setting. ()

📋 NCT03944772

Perioperative tislelizumab plus neoadjuvant chemotherapy for patients with resectable non-small-cell lung cancer: final analysis of the randomized RATIONALE-315 trial. The final analysis of the phase III RATIONALE-315 trial demonstrated that perioperative tislelizumab combined with neoadjuvant chemotherapy significantly improved overall survival and event-free survival compared to chemotherapy alone in patients with resectable stage II-IIIA non-small cell lung cancer. These clinically meaningful survival benefits, coupled with a tolerable safety profile, strongly support this regimen as a standard-of-care option for this patient population. ()

📋 NCT04379635

Deulorlatinib (TGRX-326) in ALK gene fusion positive non-small cell lung cancer after failure of second-generation inhibitors (DRAGON): a single-arm, multicenter, phase 2 trial. The novel third-generation ALK inhibitor deulorlatinib demonstrated encouraging anti-tumor activity, including a 43.7% objective response rate and robust intracranial efficacy, in patients with advanced ALK-positive non-small cell lung cancer who progressed on second-generation inhibitors. Notably, it showed strong activity against the difficult-to-treat G1202R mutation and maintained a favorable safety profile, positioning it as a promising new therapeutic option. ()

📋 NCT05955391

Time-of-day immunochemotherapy in non-small cell lung cancer: a randomized phase 3 trial. The phase 3 LungTIME-C01 trial demonstrated that administering immunochemotherapy before 15:00 h significantly improved progression-free and overall survival compared to later administration in patients with treatment-naïve advanced non-small cell lung cancer. This early time-of-day approach was associated with enhanced circulating CD8+ T cell activation and reduced exhaustion, suggesting a simple, cost-free strategy to optimize immunotherapy efficacy. ()

📋 NCT05549037

SUNRAY-01 trial protocol: an innovative study design of olomorasib and pembrolizumab with or without chemotherapy in KRAS G12C NSCLC. The SUNRAY-01 trial is investigating the efficacy and safety of combining the novel KRAS G12C inhibitor olomorasib with pembrolizumab, with or without chemotherapy, in patients with advanced KRAS G12C-mutated non-small cell lung cancer. This innovative study design aims to evaluate whether dual targeting of the KRAS pathway and immune checkpoints can overcome resistance and improve clinical outcomes in this specific molecular subgroup. ()

📋 NCT06119581

First-Line Zongertinib in Advanced HER2-Mutant Non-Small-Cell Lung Cancer. In a phase 1b trial, the novel, irreversible, HER2-selective tyrosine kinase inhibitor zongertinib demonstrated a high confirmed objective response rate of 76% and a median progression-free survival of 14.4 months as a first-line treatment for advanced HER2-mutant non-small cell lung cancer. The drug also showed promising intracranial activity and a manageable safety profile, highlighting its potential to address a significant unmet need in this patient population. ()

📋 NCT04886804

Discovery of BBO-11818, a Potent and Selective Noncovalent Inhibitor of (ON) and (OFF) KRAS with Activity against Multiple Oncogenic Mutants. BBO-11818 is a novel, orally bioavailable, noncovalent pan-KRAS inhibitor that effectively targets multiple clinically relevant KRAS mutations, including G12D and G12V, in both their active and inactive states. Preclinical data demonstrate potent inhibition of MAPK signaling and tumor regression, supporting its ongoing phase I clinical evaluation as a versatile therapeutic option for KRAS-driven malignancies. ()

📋 NCT06917079

Fecal microbiota transplantation plus immunotherapy in non-small cell lung cancer and melanoma: the phase 2 FMT-LUMINate trial. The phase 2 FMT-LUMINate trial demonstrated that healthy donor fecal microbiota transplantation (FMT) combined with first-line immune checkpoint inhibitors is safe and yields high objective response rates in patients with advanced non-small cell lung cancer and melanoma. Metagenomic analysis revealed that clinical benefit was associated with the depletion of specific deleterious bacterial species rather than simple donor strain engraftment, providing crucial insights for optimizing microbiome-based interventions. ()

📋 NCT04951583

FDG-PET/CT based small volume accelerated immuno chemoradiotherapy in locally advanced NSCLC (PACCELIO) - a randomized, open-label, multicenter phase II trial protocol. The PACCELIO phase II trial is evaluating whether integrating FDG-PET/CT to guide volume-reduced, hypofractionated chemoradiotherapy can improve treatment completion rates and facilitate successful transition to consolidation durvalumab in patients with inoperable stage III non-small cell lung cancer. This approach aims to enhance locoregional control while minimizing toxicity, potentially establishing a new, optimized standard of care for this challenging disease stage. ()

📋 NCT06102057

Baseline tumor burden and outcomes in patients with rare cancers treated with immunotherapy (Southwest Oncology Group trial S1609). In a large basket trial of rare cancers treated with dual immune checkpoint inhibitors, a larger baseline tumor burden was independently associated with worse overall survival, but not progression-free survival. However, baseline tumor burden was not predictive of tumor regression, suggesting it should be considered a prognostic rather than a predictive factor in this setting. ()

📋 NCT02834013

A Phase 1 dose-escalation study to evaluate safety, pharmacokinetics, and pharmacodynamics of OSE-279, an anti-PD-1 monoclonal antibody in patients with advanced solid tumours. The novel anti-PD-1 monoclonal antibody OSE-279 demonstrated a favorable safety profile, linear pharmacokinetics, and sustained high receptor occupancy in a phase 1 dose-escalation study involving patients with advanced solid tumors. The observation of durable objective responses supports its continued clinical development, including planned combination strategies such as therapeutic cancer vaccines in non-small cell lung cancer. ()

📋 NCT05751798

First-Line Sacituzumab Govitecan Plus Pembrolizumab and Carboplatin in Metastatic Non-Small Cell Lung Cancer: Nonsquamous and Squamous Cohorts of the EVOKE-02 Study. The phase II EVOKE-02 study demonstrated that first-line treatment with the Trop-2-directed antibody-drug conjugate sacituzumab govitecan, combined with pembrolizumab and carboplatin, yielded promising objective response rates in both nonsquamous and squamous metastatic non-small cell lung cancer. Following a dose reduction to 7.5 mg/kg to manage myelosuppression, the combination showed a tolerable safety profile, supporting further evaluation of this novel chemoimmunotherapy approach. ()

📋 NCT05186974

Alirocumab plus cemiplimab in advanced immuno-refractory metastatic non-small cell lung cancer: an ongoing multi-center phase II study. The TOP2201 phase II trial is investigating the novel combination of the PCSK9 inhibitor alirocumab and the anti-PD-1 therapy cemiplimab in patients with metastatic non-small cell lung cancer who have progressed on prior immune checkpoint blockade. Based on preclinical evidence that PCSK9 inhibition enhances antigen presentation, this study aims to determine if this strategy can overcome immunotherapy resistance and restore clinical benefit. ()

📋 NCT05553834

Participation in lung cancer biospecimen studies: an analysis of the ECOG-ACRIN phase 3 E1505 and E5508 clinical trials. An analysis of two large phase 3 lung cancer trials revealed that women, racial and ethnic minorities, and patients treated outside major academic centers are significantly less likely to participate in optional biospecimen studies. These disparities in biospecimen collection threaten the generalizability of translational research findings and highlight the need for targeted strategies to ensure diverse representation in biomarker-driven oncology studies. ()

📋 NCT01107626

Efficacy and safety of savolitinib in Chinese patients with locally advanced or metastatic MET exon 14-mutated non-small cell lung cancer: final results of a confirmatory Phase 3b study. Final results from a phase 3b confirmatory trial demonstrate that the MET inhibitor savolitinib provides robust and durable efficacy, with objective response rates of 42% in previously treated and 62% in treatment-naïve Chinese patients with MET exon 14-mutated advanced non-small cell lung cancer. The manageable safety profile and clinically meaningful survival outcomes solidify savolitinib as a standard targeted treatment option for this specific molecular subgroup. ()

📋 NCT04923945

Early ctDNA stratifies survival in locally advanced and oligometastatic lung cancer treated with radiotherapy. A novel, machine learning-derived circulating tumor fraction estimate (ctFE) from a tumor-naïve ctDNA assay effectively risk-stratified patients with locally advanced and oligometastatic non-small cell lung cancer undergoing radiotherapy. Both baseline and early on-treatment ctFE burden strongly predicted overall and progression-free survival, outperforming traditional metrics and offering a practical, noninvasive biomarker to guide precision treatment adaptation. ()

📋 NCT03916419

Four-Year Outcomes for Nivolumab With Chemotherapy and Bevacizumab in Patients With Nonsquamous NSCLC in the TASUKI-52. Four-year follow-up from the phase III TASUKI-52 trial confirms that the addition of nivolumab to carboplatin, paclitaxel, and bevacizumab provides sustained, long-term overall and progression-free survival benefits in patients with advanced nonsquamous non-small cell lung cancer. The durable responses and absence of new safety signals reinforce this combination as a highly effective first-line treatment option, particularly for patients younger than 65 and those without bone metastases. ()

📋 NCT03117049

Safety and Antitumor Activity of Farletuzumab Ecteribulin in Patients With NSCLC: Phase I Expansion Results. In a phase I expansion study, the folate receptor-alpha (FRα)-targeting antibody-drug conjugate farletuzumab ecteribulin demonstrated modest antitumor activity and a manageable safety profile in heavily pretreated patients with advanced non-small cell lung cancer. While the overall objective response rate was low, the activity observed in FRα-positive patients suggests potential utility for this targeted approach, warranting further investigation in biomarker-selected populations. ()

📋 NCT03386942

First-Line Cemiplimab for Locally Advanced NSCLC: Updated Subgroup Analyses From the EMPOWER-Lung 1 and EMPOWER-Lung 3 Trials. Updated subgroup analyses from two phase III trials demonstrate that first-line cemiplimab, either as monotherapy (for PD-L1 ≥50%) or combined with chemotherapy, significantly improves overall and progression-free survival compared to chemotherapy alone in patients with unresectable locally advanced non-small cell lung cancer who are ineligible for definitive chemoradiation. These findings, along with favorable patient-reported outcomes, support cemiplimab-based regimens as effective treatment options for this challenging patient population. ()

📋 NCT03409614

Fulzerasib plus cetuximab in first-line KRAS^G12C-mutated non-small-cell lung cancer (KROCUS): a single-arm, multicentre, phase 1b/2 trial. The combination of the KRAS G12C inhibitor fulzerasib and the anti-EGFR antibody cetuximab demonstrated a high confirmed objective response rate of 69% and a favorable safety profile as a first-line treatment for patients with KRAS G12C-mutated advanced non-small cell lung cancer. These encouraging results suggest that dual vertical pathway inhibition is a highly active strategy in this setting, supporting its advancement to phase 3 clinical trials. ()

📋 NCT05756153

Lorlatinib in patients with ALK-positive metastatic NSCLC previously treated with an ALK inhibitor: results from a phase IV study. A phase IV post-approval study confirmed the efficacy of lorlatinib in patients with ALK-positive metastatic non-small cell lung cancer who progressed on a prior second-generation ALK inhibitor, demonstrating a 42% objective response rate and robust intracranial activity. The safety profile remained consistent with earlier trials, reaffirming lorlatinib as a clinically meaningful treatment option for this previously treated patient population. ()

📋 NCT04362072

Tiragolumab Plus Atezolizumab and Chemotherapy for Advanced Nonsquamous Non-Small Cell Lung Cancer: The Phase 3 SKYSCRAPER-06 Randomized Clinical Trial. The phase 3 SKYSCRAPER-06 trial evaluating the addition of the anti-TIGIT antibody tiragolumab to atezolizumab and chemotherapy versus pembrolizumab and chemotherapy in first-line advanced nonsquamous non-small cell lung cancer was terminated early after failing to meet its primary endpoints. The combination did not improve progression-free or overall survival compared to the standard-of-care control arm, highlighting the challenges of improving upon current chemoimmunotherapy regimens in this setting. ()

📋 NCT04619797

Population-Based Modeling to Predict Human PK/PD of TAK-500, an Anti-CCR2 Antibody-Drug Conjugate for First-in-Human Study in Cancer Patients. A population pharmacokinetic-receptor occupancy model successfully integrated preclinical and clinical data to predict the human pharmacokinetics and target engagement of TAK-500, a novel anti-CCR2 antibody-drug conjugate. This quantitative framework provides a crucial foundation for guiding first-in-human dose selection and optimizing the clinical development of immune cell-directed ADCs. ()

📋 NCT04879849

Clinical Trials Summary

Number of Clinical Trials in non-small cell lung cancer updated from 2026-04-01 to 2026-04-30:

Phase 1

Phase 1/2

Phase 2

Phase 2/3

Phase 3

Phase 4

Total

Enrolling by Invitation

Not Yet Recruiting

Recruiting

188

Available

Approved for Marketing

Active, Not Recruiting

107

Completed

Total

104

329

Phase 1 Clinical Trials within 3 Months of Primary Completion Date:

DRUG

NCTID

Status

Clinical Trial Name

Completion Date

PF-08046032, Sasanlimab

NCT06870487

ACTIVE_NOT_RECRUITING

An Open-Label Phase 1 Study to Evaluate PF-08046032 as Monotherapy and Part of Combination Therapy in Participants With Advanced Malignancies

2026-04-26

MEDI5752, Carboplatin, Durvalumab, AZD2936, AZD7789, Datopotamab deruxtecan

NCT04612751

ACTIVE_NOT_RECRUITING

A Phase 1b, Multicenter, 2-Part, Open-Label Study of Datopotamab Deruxtecan (Dato-DXd) in Combination With Immunotherapy With or Without Carboplatin in Participants With Advanced or Metastatic Non-Small Cell Lung Cancer (Tropion-Lung04)

2026-05-04

BG-60366

NCT06685718

ACTIVE_NOT_RECRUITING

Phase 1a/1b, Open-Label Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of a CDAC Degrading EGFR, BG-60366, in Patients With EGFR-Mutant Non-Small Cell Lung Cancer

2026-05-15

Osimertinib, Sapanisertib

NCT02503722

ACTIVE_NOT_RECRUITING

A Phase 1 Trial of MLN0128 (TAK-228) in Combination With Osimertinib (AZD9291) in Advanced EGFR Mutation Positive Non-Small Cell Lung Cancer (NSCLC) After Progression on a Previous EGFR Tyrosine Kinase Inhibitor

2026-06-05

PF-08046049

NCT05571839

ACTIVE_NOT_RECRUITING

A Phase 1 Study of PF-08046049/SGN-BB228 in Advanced Melanoma and Other Solid Tumors

2026-06-06

S-1, RO7496353, Nab-paclitaxel, Capecitabine, Atezolizumab, Oxaliplatin, Gemcitabine, Nivolumab

NCT05867121

ACTIVE_NOT_RECRUITING

A Phase Ib, Open-label, Multicenter Dose-expansion Study Evaluating the Safety, Pharmacokinetics, and Activity of RO7496353 in Combination With a Checkpoint Inhibitor With or Without Standard-of-care Chemotherapy in Patients With Locally Advanced or Metastatic Solid Tumors

2026-06-30

Cisplatin, Elimusertib, Gemcitabine Hydrochloride

NCT04491942

ACTIVE_NOT_RECRUITING

A Phase 1 Trial of the ATR Inhibitor BAY 1895344 in Combination With Cisplatin and With Cisplatin Plus Gemcitabine in Advanced Solid Tumors With an Emphasis on Urothelial Carcinoma

2026-06-30

Phase 2 Clinical Trials within 3 Months of Primary Completion Date:

DRUG

NCTID

Status

Clinical Trial Name

Completion Date

Atezolizumab Injection; bevacizumab Injection

NCT04147351

COMPLETED

A Phase II Study of Atezolizumab in Combination With Bevacizumab, Carboplatin or Cisplatin, and Pemetrexed for EGFR-mutant Metastatic Non-small Cell Lung Cancer Patients After Failure of EGFR Tyrosine Kinase Inhibitors.

2026-02-04

IO102-IO103 in combination with pembrolizumab

NCT05077709

COMPLETED

A Phase II Multi-Arm (Basket) Trial Investigating the Safety and Efficacy of IO102-IO103 in Combination With Pembrolizumab, as First-Line Treatment for Patients With Metastatic NSCLC, SCCHN, or Metastatic mUBC

2026-02-08

Durvalumab

NCT03589547

COMPLETED

Durvalumab and Consolidation SBRT Following Chemoradiation for Locally Advanced Stage III Non-Small Cell Lung

2026-02-18

: Pembrolizumab

NCT03634241

COMPLETED

Single-Arm, Phase II of Immunotherapy With Pembrolizumab for the Prevention of Lung Cancer (IMPRINT-Lung)

2026-03-11

furmonertinib

NCT06812871

COMPLETED

A Single-arm, Multicenter, Phase 2 Study of High-dose Furmonertinib Combined With Bevacizumab and Intrathecal Pemetrexed Chemotherapy in Patients With EGFR-mutated Non-small Cell Lung Cancer and Meningeal Metastasis

2026-03-30

Tepotinib

NCT02864992

ACTIVE_NOT_RECRUITING

A Phase II Single-arm Trial to Investigate Tepotinib in Advanced (Locally Advanced or Metastatic) Non-small Cell Lung Cancer With METex14 Skipping Alterations or MET Amplification (VISION)

2026-04-30

Nab paclitaxel, Carboplatin, almonertinib

NCT06300424

ACTIVE_NOT_RECRUITING

Neoadjuvant Almonertinib Followed by Adebrelimab-based Chemo-immunotherapy in II-IIIB EGFR-mutant Non-small Cell Lung Cancer, a Single Arm, Phase II Study

2026-04-30

: Nivolumab

NCT03110978

ACTIVE_NOT_RECRUITING

Phase II Randomized Clinical Trials Comparing Immunotherapy Plus Stereotactic Ablative Radiotherapy (I-SABR) Versus SABR Alone for Stage I, Selected Stage IIa, or Isolated Lung Parenchymal Recurrent Non-Small Cell Lung Cancer: I-SABR

2026-06-30

Adagrasib

NCT05673187

ACTIVE_NOT_RECRUITING

A Multicentre, Single-arm Phase II Trial of Adagrasib in Patients With KRASG12C-mutant NSCLC, Including the Elderly (≥70 Years) or Patients With Poor Performance Status

2026-07

Osimertinib, : Bevacizumab

NCT02971501

ACTIVE_NOT_RECRUITING

A Phase II Trial of Osimertinib (AZD9291) With or Without Bevacizumab in Patients With EGFR Mutation Positive NSCLC and Brain Metastases

2026-07-01

Patritumab Deruxtecan (Up-Titration), Patritumab Deruxtecan (Fixed dose)

NCT04619004

ACTIVE_NOT_RECRUITING

HERTHENA-Lung01: A Phase 2 Randomized Open-Label Study of Patritumab Deruxtecan (U3-1402) in Subjects With Previously Treated Metastatic or Locally Advanced EGFR-mutated Non-Small Cell Lung Cancer (NSCLC)

2026-07-03

Phase 3 Clinical Trials within 3 Months of Primary Completion Date:

DRUG

NCTID

Status

Clinical Trial Name

Completion Date

Keytruda-EU, GME751

NCT06159790

COMPLETED

A Randomized, Double-blind, Parallel-group Study to Compare Efficacy, Safety, and Immunogenicity of GME751 (Proposed Pembrolizumab Biosimilar) and EU-authorized Keytruda® in Adult Participants With Untreated Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC)

2026-03-16

BL-B01D1, Pemetrexed+Cisplatin or Carboplatin

NCT06382116

ACTIVE_NOT_RECRUITING

A Phase III Randomized Controlled Clinical Study Comparing BL-B01D1 With Platinum Based Chemotherapy (First-line of Systemic Treatment) in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer After EGFR-TKI Failure

2026-05

Pemetrexed, : Pembrolizumab, Carboplatin, Nab-paclitaxel, Paclitaxel

NCT06096844

RECRUITING

A Randomized Phase III Trial of Chemo-Immunotherapy vs Immunotherapy Alone for the Vulnerable Older Adult With Advanced Non-Small Cell Lung Cancer: The ACHIEVE Study

2026-06-01

AMG 510, Docetaxel

NCT04303780

ACTIVE_NOT_RECRUITING

A Phase 3 Multicenter, Randomized, Open Label, Active-controlled, Study of AMG 510 Versus Docetaxel for the Treatment of Previously Treated Locally Advanced and Unresectable or Metastatic NSCLC Subjects With Mutated KRAS p.G12C

2026-06-24

Phase 4 Clinical Trials within 3 Months of Primary Completion Date:

No phase 4 trials completing within the next three months.

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