Rybrevant (amivantamab-vmjw) / Genmab, J&J - LARVOL DELTA

Amivantamab plus Chemotherapy in NSCLC with EGFR Exon 20 Insertions. (PubMed, N Engl J Med) - P3 | "The use of amivantamab-chemotherapy resulted in superior efficacy as compared with chemotherapy alone as first-line treatment of patients with advanced NSCLC with EGFR exon 20 insertions. (Funded by Janssen Research and Development; PAPILLON ClinicalTrials.gov number, NCT04538664.)."

EGFR exon 20 • Journal • Hematological Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

A Single-Arm Phase 2 Study of First-Line Amivantamab, Lazertinib, Pemetrexed in EGFR-mutant NSCLC: AMIGO-1 (LACOG 0821) (IASLC-WCLC 2026) - P2 | "A one-group chi-square test (one-sided alpha = 0.10) had 80% power to detect improvement from 50% (historical osimertinib - standard therapy when AMIGO-1 was designed) to 65% with 49 pts. Toxicity may have limited overall benefit. These findings support further evaluation of AMI+L+ pemetrexed, especially in poor prognostic pts."

Clinical • P2 data • Febrile Neutropenia • Infectious Disease • Lung Cancer • Neutropenia • Non Small Cell Lung Cancer • Pancreatitis • Solid Tumor • EGFR • TP53

First-line Amivantamab-chemotherapy vs Chemotherapy in NSCLC with EGFR Exon 20 Insertions: Overall Survival from PAPILLON (IASLC-WCLC 2026) - P3 | "In the phase 3 PAPILLON study (NCT04538664; median follow-up: 14.9 months), first-line amivantamab plus carboplatin-pemetrexed (amivantamab-chemotherapy) significantly improved median progression-free survival by blinded independent central review (BICR) versus chemotherapy (11.4 vs 6.7 months; HR, 0.40; 95% CI, 0.30-0.53; P <0.001) in participants with Ex20ins advanced NSCLC (Zhou NEJM 2023). OS was extended by a clinically meaningful 6 months with amivantamab-chemotherapy versus chemotherapy (34.3 vs 27.9 months) despite extensive (76%) subsequent amivantamab use in the chemotherapy arm. While crossover likely attenuated the HR-based OS estimate, the adjusted OS analysis showed a substantially longer estimated survival benefit, supporting amivantamab-chemotherapy as a foundational first-line regimen for patients with Ex20ins advanced NSCLC."

Clinical • EGFR exon 20 • Late-breaking abstract • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • EGFR

Phase 1 Global Study of Iza-Bren in Patients With Metastatic EGFR-mutated NSCLC: Results of the Randomized Dose Expansion Cohort (IASLC-WCLC 2026) - P1 | "The median number of prior line of therapy was 2 (range 1-7); all pts had progressed on a third generation EGFR inhibitor, 64% progressed on platinum-based chemotherapy and 18% progressed on amivantamab. Primary G-CSF prophylaxis was associated with an improved safety profile. The totality of the safety, efficacy and PK data support 2.5 mg/kg D1D8 Q3W as the RP3D in the global registrational study (IZABRIGHT-Lung01) in EGFR-mutated NSCLC after progression on a third generation EGFR inhibitor (NCT05983432)."

Clinical • Metastases • P1 data • Febrile Neutropenia • Inflammation • Lung Cancer • Neutropenia • Non Small Cell Lung Cancer • Pneumonia • Solid Tumor • Thrombocytopenia • EGFR

Anti-Tumor Activity of BH-30643, a Novel Macrocyclic EGFR TKI, in Patients With Secondary EGFR Resistance Mutations (IASLC-WCLC 2026) - P1/2 | "Responses were observed across different C797S co-mutations (e.g., exon 19 del, L858R, G719S, T790M) and following different targeted therapies (e.g., osimertinib, afatinib, amivantamab). Conclusions : BH-30643 can achieve clinical and molecular responses in heavily pretreated NSCLC patients with secondary EGFR resistance mutations across diverse molecular contexts, supporting its potential as monotherapy in the treatment of resistance to 3rd-generation EGFR TKIs. Expansion cohort enrollment is ongoing with a focus on C797S-positive resistance."

Clinical • First-in-human • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2 • KRAS • MET

SKIPPirr: Premedication to Reduce Amivantamab Associated Infusion Related Reactions (clinicaltrials.gov) - P2 | N=68 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Mar 2027 ➔ Sep 2027

Trial completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

OrigAMI-1: A Study of Amivantamab Monotherapy and in Addition to Standard-of-Care Chemotherapy in Participants With Advanced or Metastatic Colorectal Cancer (clinicaltrials.gov) - P1/2 | N=225 | Recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Oct 2030 ➔ May 2031

Monotherapy • Trial completion date • Colon Adenocarcinoma • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • BRAF • HER-2 • KRAS • NRAS • TYK2

CHRYSALIS: Study of Amivantamab, a Human Bispecific EGFR and cMet Antibody, in Participants With Advanced Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=751 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Dec 2026 ➔ Dec 2027

First-in-human • Trial completion date • Lung Adenocarcinoma • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • MET

Real-World Experience with Amivantamab in EGFR-Mutant Lung Cancer (ESMO 2026) - No abstract available

Clinical • Real-world • Real-world evidence • Lung Cancer • Oncology • Solid Tumor • EGFR

Indirect comparison of amivantamab (ami) with real-world therapies in recurrent/metastatic head & neck squamous cell carcinoma (R/M HNSCC) after immune checkpoint inhibitor (ICI) and platinum-based chemotherapy (ESMO 2026) - No abstract available

Checkpoint inhibition • Clinical • Metastases • Real-world • Real-world evidence • Head and Neck Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Amivantamab in subjects with aberrant MET and/or EGFR solid tumors –Results from the Baskets of Baskets trial Module-3 (ESMO 2026) - No abstract available

Clinical • Oncology • Solid Tumor • EGFR

Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: Primary results from the phase 3 MARIPOSA-2 study. (PubMed, Ann Oncol) - "Amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy improved progression-free survival and intracranial progression-free survival versus chemotherapy in a population with limited options after disease progression on osimertinib. Longer follow-up is needed for the modified amivantamab-lazertinib-chemotherapy regimen."

Journal • Metastases • P3 data • Hematological Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Amivantamab in patients with NSCLC with MET exon 14 skipping mutation: Updated results from the CHRYSALIS study. (ASCO 2022) - P1 | "Median age was 70 y (range, 43-88), 58% were women, median prior lines of therapy was 2 (range, 0-10) [eg, crizotinib (n=13), capmatinib (n=11), tepotinib (n=5), anti-MET antibody (n=1)], and 23% had history of brain metastases at baseline. Amivantamab demonstrates anti-tumor activity in primary METex14 NSCLC including after prior MET inhibitor treatment. Enrollment is ongoing and updated data will be shown."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • MET

Amivantamab plus chemotherapy vs chemotherapy as first-line treatment in EGFR Exon 20 insertion-mutated advanced non-small cell lung cancer (NSCLC): Primary results from PAPILLON, a randomized phase III global study (ESMO 2023) - P3 | "Ami combined with carboplatin/pemetrexed (ami-chemo) demonstrated safety and antitumor activity in the phase 1 CHRYSALIS study. Safety profile was consistent with that of each individual agent. PAPILLON establishes ami-chemo as the new first-line standard of care in EGFR Ex20ins advanced NSCLC."

Clinical • EGFR exon 20 • Late-breaking abstract • Metastases • P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

MARIPOSA-2: A Study of Amivantamab and Lazertinib in Combination With Platinum-Based Chemotherapy Compared With Platinum-Based Chemotherapy in Patients With Epidermal Growth Factor Receptor (EGFR)-Mutated Locally Advanced or Metastatic Non- Small Cell Lung Cancer After Osimertinib Failure (clinicaltrials.gov) - P3 | N=776 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Nov 2027 ➔ Jul 2028

Trial completion date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Amivantamab and Lazertinib in Combination With Platinum-Based Chemotherapy in Relapsed/Refractory EGFR-mutant NSCLC (IASLC-WCLC 2022) - P1 | " The LACP (lazertinib, amivantamab, carboplatin, pemetrexed) cohort of the CHRYSALIS-2 study (NCT04077463) enrolled patients with EGFR-mutant NSCLC whose disease progressed on or after treatment with an EGFR TKI as last line of therapy (maximum of 3 prior lines)... Enrolled patients have received a median of 2 (range, 1-3) prior lines of therapy, including osimertinib (n=14), gefitinib (n=3), and afatinib (n=3)... Amivantamab in combination with lazertinib and chemotherapy yielded high overall response rates in patients who progressed on EGFR TKIs as prior line of therapy. The safety profile of the LACP regimen was consistent with the individual agents, with no evidence of new safety signals or additive toxicity."

Combination therapy • Fatigue • Hematological Disorders • Lung Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thrombocytopenia • EGFR

Subcutaneous amivantamab vs intravenous amivantamab, both in combination with lazertinib, in refractory EGFR-mutated, advanced non-small cell lung cancer (NSCLC): Primary results, including overall survival (OS), from the global, phase 3, randomized controlled PALOMA-3 trial. (ASCO 2024) - P3 | "PALOMA-3 (NCT05388669) evaluated SC ami+laz vs IV ami+laz for pharmacokinetics (PK), efficacy, and safety among pts with EGFR Ex19del or L858R-mutated advanced NSCLC and disease progression on osimertinib and platinum-based chemotherapy. SC ami demonstrated noninferior PK and ORR compared to IV. Unexpectedly, DoR, PFS, and OS were longer in the SC arm vs IV, suggesting that the route of administration or formulation may affect outcomes. The safety profile was improved for SC ami, with lower IRR and VTE rates."

Clinical • Combination therapy • Late-breaking abstract • Metastases • P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Amivantamab plus chemotherapy vs chemotherapy as a first-line treatment among Asian patients with EGFR exon 20 insertion-mutated advanced non-small cell lung cancer (NSCLC): PAPILLON subgroup analysis (ESMO Asia 2023) - P3 | "In the global, phase 3 PAPILLON study (NCT04538664), ami and carboplatin-pemetrexed (ami-chemo) significantly improved progression-free survival (PFS) vs chemo (data submitted to ESMO 2023) in treatment naïve patients (pts) with Ex20ins advanced NSCLC. Conclusions Ami-chemo demonstrated superior PFS vs chemo in Asian pts with a tolerable safety profile. These results were consistent with those of the overall population."

Clinical • EGFR exon 20 • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Amivantamab plus chemotherapy vs chemotherapy in EGFR-mutated, advanced non-small cell lung cancer after disease progression on osimertinib: Second interim overall survival from MARIPOSA-2 (ESMO 2024) - P3 | "Background: In the phase 3 MARIPOSA-2 study (NCT04988295), amivantamab (ami)-chemotherapy (chemo; carboplatin/pemetrexed) showed superior progression-free survival (PFS) vs chemo in patients (pts) with EGFR-mutant, advanced non-small cell lung cancer (NSCLC) after progression on osimertinib (osi; HR, 0.48; 95% CI, 0.36–0.64; P<0.001). Ami-chemo numerically improved OS and significantly prolonged post-progression outcomes vs chemo in EGFR-mutant, advanced NSCLC post-osi."

Clinical • Late-breaking abstract • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • EGFR

Amivantamab plus chemotherapy (with or without lazertinib) vs chemotherapy in EGFR-mutated advanced NSCLC after progression on osimertinib: MARIPOSA-2, a phase III, global, randomized, controlled trial (ESMO 2023) - P3 | "Background Amivantamab (ami), an EGFR-MET bispecific antibody with immune cell-directing activity, plus carboplatin-pemetrexed (chemo) with and without lazertinib (laz), a CNS-penetrant, 3rd-gen EGFR TKI, have demonstrated antitumor activity in phase 1 studies. The impact of modifying the ami-laz-chemo regimen on safety and efficacy requires longer follow-up. Conclusions Ami-chemo and ami-laz-chemo improved PFS, ORR, and intracranial PFS vs chemo in EGFR-mutated advanced NSCLC after progression on osi and may represent a new standard of care."

Clinical • Late-breaking abstract • Metastases • P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Overall survival of first-line amivantamab plus lazertinib in atypical EGFR-mutated advanced non-small cell lung cancer (NSCLC): Updated results from the CHRYSALIS-2 study. (ASCO 2026) - P1 | "Afatinib, approved for atypical EGFR-mutated NSCLC, showed a median overall survival (OS) of 19.4 months among 38 participants (pts) with atypical EGFR-mutations globally (Yang Lancet Oncol 2015)...In MARIPOSA, first-line (1L) ami plus lazertinib (ami-laz) significantly prolonged OS vs osimertinib (HR, 0.75; P=0.005) in cEGFR-mutated NSCLC... 1L treatment of atypical EGFR-mutated advanced NSCLC with ami-laz resulted in a clinically meaningful median OS of nearly 3.5 years. Many pts were able to stay on 1L treatment long term, with 20% still ongoing. Ami-laz has now shown substantial survival benefit in both 1L cEGFR- and atypical EGFR-mutated disease."

Clinical • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Amivantamab plus chemotherapy vs chemotherapy in EGFR-mutant advanced NSCLC after progression on osimertinib: Secondary analyses of patient-relevant endpoints from MARIPOSA-2 (ELCC 2024) - P3 | "In MARIPOSA-2 (NCT04988295), ami plus carboplatin-pemetrexed (ami-chemo) significantly prolonged progression-free survival (PFS) vs chemo (HR, 0.48; P<0.001) in patients (pts) with EGFR-mutant advanced NSCLC after progression on osimertinib (Passaro Ann Oncol 2023). Conclusions Ami-chemo numerically prolonged TTSP vs chemo. More pts in the ITT population reported improved or stable functioning and absence of lung cancer-related symptoms for ami-chemo vs chemo in pts with EGFR-mutant advanced NSCLC after disease progression on osimertinib."

Clinical • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Amivantamab, lazertinib and bevacizumab in EGFR-mutant advanced NSCLC with acquired resistance to 3rd generation EGFR-TKI: Final results from the phase II ETOP AMAZE-lung trial (ELCC 2025) - P2 | "Amivantamab (ami), an EGFR-MET bispecific antibody, is approved in combination with chemotherapy for EGFR-mutant NSCLC patients (pts) after progression on osimertinib (osi) based on the MARIPOSA-2 trial. Ami-laz-bev combination demonstrated durable antitumour activity and represents a promising chemo-sparing alternative after progression on osi. Safety was consistent with known toxicity profiles."

Clinical • Metastases • P2 data • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Amivantamab plus FOLFOX or FOLFIRI in metastatic colorectal cancer: Results from OrigAMI-1, an open-label, phase Ib/II study (ESMO 2024) - P1/2 | "With its unique mechanism of action, ami may offer improved efficacy and manageable safety when combined with FOLFOX or FOLFIRI. OrigAMI-1 (NCT05379595) is assessing the safety and efficacy of ami (1050 mg [1400 mg if ≥80kg]) plus mFOLFOX6 or FOLFIRI in anti-EGFR-naïve RAS/RAF WT mCRC... Ami+chemotherapy demonstrated encouraging, durable antitumor activity and a manageable safety profile in anti-EGFR-naïve RAS/RAF WT mCRC."

Clinical • Metastases • P1/2 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BRAF • HER-2 • KRAS • NRAS

Pivotal topline data from the phase 1/2 TRIDENT-1 trial of repotrectinib in patients with ROS1+ advanced non-small cell lung cancer (NSCLC) (AACR-NCI-EORTC 2022) - P1/2 | "He played a monumental role in developing repotrectinib, lazertinib, amivantamab, and other targeted- and immuno-therapies, many of which were acknowledged for breakthrough therapy designation and FDA approval. Repotrectinib achieves durable activity, including intracranial responses, in TKI-naïve and TKI-pretreated patients with ROS1+ advanced NSCLC, and those with ROS1 G2032R. Repotrectinib safety is well characterized, manageable, and compatible with long-term use."

Clinical • Late-breaking abstract • P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ROS1