Tag: #ASCO26

#ASCO26 News: Teclistamab Monotherapy Improves PFS and OS in Early RRMM

Results from the phase 3 MajesTEC-9 trial, presented on Day 1 of the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, showed that teclistamab monotherapy significantly improved progression-free survival (PFS) and overall survival (OS) compared with investigator’s choice of pomalidomide, bortezomib, and dexamethasone (PVd) or carfilzomib and dexamethasone (Kd) in patients with relapsed or refractory multiple myeloma (RRMM) who had received 1 to 3 prior lines of therapy, including lenalidomide and an anti-CD38 monoclonal antibody. The findings were published simultaneously in the New England Journal of Medicine.

The open-label, multicenter trial enrolled patients with documented progression or lack of response to their last regimen. Patients who had received prior BCMA-directed therapy were excluded from the study. Patients were randomly assigned 1:1 to teclistamab monotherapy (n = 296) or PVd or Kd (n = 297). The primary endpoint of the study was independent review committee (IRC)–assessed PFS.

At a median follow-up of 17.3 months, median PFS was not reached with teclistamab vs 8.2 months with PVd or Kd. Estimated 18-month PFS was 69.8% vs 26.9%, respectively, corresponding to an HR for progression or death of 0.29 (95% CI, 0.23-0.38; P < .001).

The overall response was 84.5% with teclistamab vs 54.2% on PVd or Kd. Patients on the teclistamab arm had deeper responses with a complete response or better response occurring in 65.9% of patients on teclistamab vs 16.8% with PVd or Kd (P < .001). MRD-negative complete response or better was reported in 38.5% vs 6.7%, respectively.

Overall survival was also significantly improved with teclistamab treatment. The estimated 18-month OS was 79.2% with teclistamab and 68.6% with PVd or Kd, with an HR for death of 0.60 (95% CI, 0.43-0.83; P = .002).

Grade 3 or 4 adverse events occurred in 84.9% of patients receiving teclistamab and 76.3% receiving PVd or Kd. Cytokine release syndrome occurred in 66.0% of teclistamab-treated patients, mostly grade 1 or 2, and ICANS occurred in 4.1%. Grade 3 or 4 infections occurred in 41.6% and 29.0%, respectively. Grade 5 adverse events occurred in 6.5% and 3.5%, respectively. In both arms, most of the adverse event-related deaths were due to infection.

In a New England Journal accompanying editorial, María-Victoria Mateos, PhD, described MajesTEC-9 as a landmark trial that supports teclistamab monotherapy as a pragmatic and accessible BCMA-targeted approach in early relapse, while emphasizing that broader use will depend on infection prevention, patient selection, and sequencing.

Table. Key Efficacy Outcomes in MajesTEC-9

	Teclistamab (n = 296)	PVd or Kd (n = 297)	HR (95% CI); P
Median PFS, mo	NR	8.2	0.29 (0.23-0.38); P < .001
18-mo PFS, %	69.8	26.9
Median OS, mo	NR	NR	0.60 (0.43-0.83); P = .002
18-mo OS, %	79.2	68.6
ORR, %	84.5	54.2
≥CR, %	65.9	16.8
≥MRD-negative CR, %	38.5	6.7

Abbreviations: BCMA, B-cell maturation antigen; CR, complete response; ICANS, immune effector cell–associated neurotoxicity syndrome; Kd, carfilzomib and dexamethasone; MRD, minimal residual disease; NR, not reached; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; PVd, pomalidomide, bortezomib, and dexamethasone.

References

Mina R, et al. MajesTEC-9: Phase 3 study of teclistamab monotherapy vs investigator’s choice of PVd or Kd in patients with relapsed or refractory multiple myeloma after 1 to 3 prior lines of therapy. Presented at: ASCO Annual Meeting 2026; Day 1; Abstract 7507.

Touzeau C, Mina R, Quach H, et al; MajesTEC-9 Trial Investigators. Teclistamab in multiple myeloma with one to three previous lines of therapy. N Engl J Med. Published May 29, 2026. doi:10.1056/NEJMoa2603870

Mateos M-V. Redefining early relapse in multiple myeloma — time to change the rules. N Engl J Med. Published May 29, 2026. doi:10.1056/NEJMe2605404

May 30, 2026

#ASCO26: First-Line Sunvozertinib Prolongs PFS in EGFR Exon 20 Insertion–Mutated Advanced NSCLC

The oral EGFR tyrosine kinase inhibitor sunvozertinib significantly improved progression-free survival (PFS) compared with carboplatin–pemetrexed as first-line treatment for advanced nonsquamous non–small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations in the phase 3, international WU-KONG28 trial. Results of the primary analysis were reported in an opening Oral Abstract Session at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting and published simultaneously in the New England Journal of Medicine.

WU-KONG28 enrolled adults with previously untreated, locally advanced stage IIIB or IIIC or metastatic stage IV nonsquamous NSCLC harboring EGFR exon 20 insertions, an Eastern Cooperative Oncology Group performance-status score of 0 or 1, and adequate organ function. Patients with brain metastases were eligible if the metastases were stable after local therapy. From December 2022 through May 2025, 324 patients from 154 sites in 15 countries were randomly assigned 1:1 to oral sunvozertinib 300 mg once daily (n = 163) or carboplatin–pemetrexed administered every 3 weeks for up to 4 or 6 cycles, at investigator discretion, followed by pemetrexed maintenance therapy (n = 161). Randomization was stratified by baseline brain metastasis status. Patients in the chemotherapy group could cross over to sunvozertinib after disease progression was confirmed by blinded independent central review (BICR).

The primary end point was BICR-assessed PFS according to RECIST version 1.1. The key secondary end point was overall survival (OS); other secondary end points included investigator-assessed PFS, objective response, change in tumor size, and duration of response. The data cutoff for the primary analysis was January 16, 2026.

At a median follow-up of 24.0 months in the sunvozertinib group and 18.0 months in the chemotherapy group, median BICR-assessed PFS was 10.3 months with sunvozertinib compared with 7.5 months with chemotherapy. Sunvozertinib reduced the risk of disease progression or death by 35% (HR, 0.65; 95% CI, 0.50–0.85; P < .001). PFS rates at 12 months were 46.1% and 26.7%, respectively; at 18 months, rates were 33.2% and 17.1%; and at 24 months, rates were 23.0% and 10.3%.

Objective response by BICR was reported in 58.9% of patients treated with sunvozertinib compared with 31.1% of those treated with chemotherapy. Median best percentage change from baseline in tumor size was −42.1% with sunvozertinib and −24.7% with chemotherapy. Median duration of response was 11.2 months and 7.1 months, respectively.

OS data were immature at 38.9% maturity. At a median OS follow-up of 26.1 months with sunvozertinib and 26.7 months with chemotherapy, 62 and 64 patients, respectively, had died. Median OS was 29.8 months with sunvozertinib and 28.8 months with chemotherapy (HR, 0.99; 95% CI, 0.70–1.40; P = .48). Interpretation of OS is limited by maturity and the crossover design: among 112 patients in the chemotherapy group with BICR-confirmed disease progression, 101 (90.2%) crossed over to sunvozertinib.

Safety analyses included 163 patients treated with sunvozertinib and 150 treated with chemotherapy. Grade 3 or higher adverse events occurred in 75.5% and 56.7% of patients, respectively. The most common grade 3 or higher adverse events with sunvozertinib were increased serum creatine kinase level (20.9%), diarrhea (14.1%), and anemia (9.2%); with chemotherapy, the most common were decreased neutrophil count (18.7%), anemia (11.3%), decreased white-cell count (6.7%), and decreased platelet count (6.7%). Serious adverse events were reported in 45.4% of patients receiving sunvozertinib and 26.7% receiving chemotherapy.

Adverse events led to drug discontinuation in 11.7% of patients treated with sunvozertinib and 12.0% treated with chemotherapy; treatment-related adverse events led to discontinuation in 7.4% and 11.3%, respectively. Interstitial lung disease and pneumonitis led to sunvozertinib discontinuation in 1.8% and 1.2% of patients. No treatment-related fatal adverse events occurred with sunvozertinib; 1 treatment-related fatal pneumonia event occurred in the chemotherapy group.

Table. Key Efficacy Outcomes in WU-KONG28

Endpoint	Sunvozertinib (n = 163)	Chemotherapy (n = 161)
Median PFS by BICR, mo	10.3	7.5
HR (95% CI); P	0.65 (0.50–0.85); < .001
PFS at 12 mo, %	46.1	26.7
PFS at 18 mo, %	33.2	17.1
PFS at 24 mo, %	23.0	10.3
Objective response by BICR, %	58.9	31.1
Median DOR, mo	11.2	7.1
Median OS, mo	29.8	28.8
OS at 24 mo, %	57.4	56.2

Abbreviations: BICR, blinded independent central review; CI, confidence interval; EGFR, epidermal growth factor receptor; HR, hazard ratio; NSCLC, non–small-cell lung cancer; OS, overall survival; PFS, progression-free survival; DOR, duration of response.

References

May 29, 2026