NMPA : New batch of drugs or therapies for non-small cell lung cancer in 2024

Toripalimab

NMPA approved the use of Toripalimab in adult patients with resectable stage ⅢA-ⅢB non-small cell lung cancer.

Unecritinib

NMPA approved Unecritinib for the treatment of adult patients with ROS1 positive locally advanced or metastatic non-small cell lung cancer.

Repotrectinib

NMPA approved Repotrectinib for adult patients with ROS1 positive locally advanced or metastatic non-small cell lung cancer.

Rezivertinib

NMPA approved Rezivertinib for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer who developed disease during or after EGFR T790M treatment and had positive EGFR T790M mutation.

Ivonescimab

NMPA approved Ivonescimab combined with pemetrexed and carboplatin for the treatment of locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) with EGFR mutation after EGFR TKI treatment.

Rilertinib

NMPA approved the use of Rilertinib in the treatment of adult patients with locally advanced or metastatic NSCLCwho had developed disease before or after EGFR-TKI treatment and were confirmed to have EGFR T790M mutation.
It is also suitable for the treatment of adult patients with advanced NSCLCwho have received at least one systemic treatment KRAS G12C mutant.

Capmatinib

NMPA approved Capmatinib for adult patients with locally advanced or metastatic NSCLC who have not been systematically treated and carry the jumping mutation of exon 14 of MET.

Osimertinib

NMPA approved Osimertinib combined with chemotherapy as the first-line treatment for advanced NSCLC with EGFR mutation.

Alectinib

NMPA approved Alectinib for postoperative adjuvant therapy in patients with ALK-positive NSCLC after complete tumor resection.

Fulzerasib

NMPA approved the use of Fulzerasib in the treatment of adult patients with KRAS G12C mutant advanced NSCLC who had received at least one systemic treatment.

Garsorasib

NMPA approved the use of Fulzerasib in the treatment of adult patients with KRAS G12C mutant advanced NSCLC who had received at least one systemic treatment.

FDA : New batch of drugs or therapies for non-small cell lung cancer in 2024

Tepotinib

FDA approved Tepotinib from Merck Serono for the treatment of adult patients with metastatic NSCLC with exon 14 skipping.

Osimertinib

FDA approved Osimertinib for the treatment of locally advanced, unresectable (stage III) NSCLC adults with EGFR exon 19 deletion or exon 21 L858R mutation. These patients did not progress during or after concurrent or sequential platinum-based radiotherapy and chemotherapy.

Alectinib

FDA approved Aletinib as an adjuvant therapy for patients with ALK-positive NSCLC after complete tumor resection.

Durvalumab

FDA approved Durvalumab combined with platinum-containing chemotherapy as a neoadjuvant therapy, and duvalizumab as an adjuvant therapy after operation for resectable (tumor ≥100px and/or lymph node positive) adult patients with NSCLC, who have no known EGFR mutation or ALK rearrangement.

Lazertinib

FDA approved Lazertinib combined with Amivantamab-vmjw for the first-line treatment of locally advanced or metastatic NSCLC patients with deletion of exon 19 of EGFR or missense mutation of exon 21.

Amivantamab-vmjw

FDA approved the combination of Avantotuzumab, Carboplatin and Pemetrexed as the first-line treatment for locally advanced or metastatic NSCLC patients with EGFR exon 20 insertion mutation.

CDE of NMPA and BTD of FDA in 2024

Furmonertinib

CDE

Furmonertinib was listed as a "breakthrough therapeutic variety" by CDE, and the proposed indication is: first-line treatment for adult patients with locally advanced or metastatic NSCLC with EGFR 20 exon 20 insertion mutation.

Telisotuzumab

Telisotuzumabwas listed as a "breakthrough therapeutic variety" by CDE, and the proposed indication is: it is used to treat patients with advanced/metastatic EGFR wild-type (WT) non-squamous (NSq) NSCLC with high expression of c-Met protein during or after platinum drug treatment.

Lorlatinib

Loratinib was listed as a "quasi-breakthrough therapeutic variety" by CDE, and the proposed indication is: for patients with locally advanced or metastatic ROS1 positive non-small cell lung cancer after crizotinib and platinum-containing chemotherapy.

BAY 2927088

BAY 2927088 was listed as a "quasi-breakthrough therapeutic variety" by CDE, and the proposed indication is: to treat adult patients with HER2(ERBB2) activation mutation who have previously received a systemic treatment for unresectable or metastatic NSCLC.

Osimertinib

Osimertinib was listed as a "quasi-breakthrough therapeutic variety" by CDE, and the proposed indication is: it is used for the treatment of locally advanced, unresectable (stage III) NSCLC adults who have no disease progression after receiving radical radiotherapy and chemotherapy containing platinum and have exon 19 deletion (Ex19del) or exon 21(L858R) substitution mutation.

Sutetinib

Sutetinib was listed as a "breakthrough therapeutic variety" by CDE, and it is intended to be used to treat locally advanced or metastatic NSCLC only non-drug-resistant rare EGFR mutations, including L861Q, G719X and/or S768I.

BI 1810631

BI 1810631 was listed as a "breakthrough therapeutic variety" by CDE, and the proposed indication is: it is used to treat adult patients with advanced, unresectable or metastatic NSCLC who have received systemic treatment before.

Almonertinib

Almonertinib was listed as a "breakthrough therapeutic variety" by CDE, and the proposed indication is: it is used for the treatment of patients with unresectable locally advanced e EGFR exon 19 deletion or exon 21(L858R) substitution mutation without disease progression after radical radiotherapy and chemotherapy containing platinum.

BL-B01D1

BL-B01D1 was listed in the "Breakthrough Treatment Variety" by CDE, and the proposed indications are: 1) patients with locally advanced or metastatic EGFR wild-type non-small cell lung cancer who were previously treated with anti-PD-1/PD-L1 monoclonal antibody and failed to receive platinum-containing chemotherapy; 2) Patients with locally advanced or metastatic non-squamous NSCLC with EGFR-sensitive mutation who failed to be treated with EGFR-TKI.

DZD9008

Locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutation without systematic treatment.

BAY 2927088

BTD

BAY 2927088 has been recognized by FDA as a breakthrough therapy (BTD), which is used to treat patients with unresectable or metastatic non-small cell lung cancer who have received systemic therapy before and carry HER2 mutation.

NVL-520

NVL-520 has been recognized by FDA as a breakthrough therapy (BTD), which is used to treat patients with metastatic non-small cell lung cancer who have been treated with two ROS1 kinase inhibitors in the past and carry ROS1 positive mutations.

Alectinib

The FDA approved Alectinib as an adjuvant therapy for patients with ALK-positive NSCLC after complete tumor resection.

Sunvozertinib

Sunvozertinib has been recognized by FDA as a breakthrough therapy (BTD) for first-line treatment of locally advanced or metastatic NSCLC patients with EGFR exon 20 insertion mutation.

NVL655

NVL-655 has been approved by FDA as a breakthrough therapy (BTD) for the treatment of locally advanced or metastatic ALK-positive NSCLC.

Update points

Molecular typing

For operable stage I-III NSCLC, grade I recommended guided adjuvant immunotherapy with PD-L1 expression detection for additional postoperative stage II/III NSCLC, and grade II recommended guided adjuvant targeted therapy with ALK fusion detection.

Non-Surgical Stages III and IV

Grade II recommendation for immunohistochemistry of MET protein overexpression in newly added tumor tissues.

Stage IA and IB treatment

With the addition of the Class II recommendation for SABR combined with immunotherapy, SABR combined with immunotherapy significantly increased the 4-year EFS rate in patients with early or isolated relapsed NSCLC compared to SABR.

IIA、IIB

Primary treatment

Targeting

New radical surgery and ALK fusion detected after surgery, grade II recommendation for adjuvant treatment with Alectinib after surgery.

Perioperative period

Grade II recommendations for the addition of platinum-containing chemotherapy combined with Nivolumab+adjuvant treatment with Pembrolizumab/Tislelizumab, Grade III recommendations for platinum-containing chemotherapy combined with Nivolumab+adjuvant treatment with Durvalumab, and Grade III recommendations for Nivolumab platinum-containing chemotherapy combined with Nivolumab adjuvant treatment after Nivolumab treatment.

Operable in Stage IIIA/IIIB(T3N2M0)

Auxiliary targeting

New radical surgery and ALK fusion detected after surgery, grade II recommendation for adjuvant treatment with Alectinib after surgery.

Perioperative immunity

New grade I recommendations for platinum-containing chemotherapy combined with Nivolumab+adjuvant treatment with Toripalimab, grade II recommendations for platinum-containing chemotherapy combined with Nivolumab+adjuvant treatment with Pembrolizumab/Tislelizumab, grade III recommendations for platinum-containing chemotherapy combined with Nivolumab+adjuvant treatment with Durvalumab, and grade III recommendations for Nivolumab platinum-containing chemotherapy combined with Nivolumab adjuvant treatment after Nivolumab treatment.

later period

EGFR sensitive mutation

Grade I recommendation for new first-line treatment of Befotertinib and Grade II recommendation for combination chemotherapy of Osimertinib.

EGFRex20ins mutation

A new first-line treatment of Amivantamab combined with platinum-based two-drug chemotherapy was recommended in Grade III and Sunvozertinib in Grade I, and the second-line treatment of Mobocertinib was cancelled.

ALK Fusion

Grade I recommendations for Iruplinalib as an additional first-line treatment following resistance to Iruplinalib and Crizotinib.

ROS1 Fusion

With the addition of first-line and second-line treatments, the Repotrectinib is proposed as a Grade III treatment, with Unecritinib included in the written description and approved for marketing by NMPA.

MET14 exon

skip

The first-line treatment and the second-line treatment increase the recommendation of Tepotinib to grade I, and add the recommendation of Glumetinib and Bozitinib to grade I, and the recommendation of first-line treatment of Savolitinib to grade II.

BRAF V600E

New Encorafenib+Binimetinib Class III recommendation.

RET Fusion

First-line treatment increased the recommendation of Pralsetinib for Grade I, and the type of evidence recommended for Selpercatinib for Grade I was changed from Class 3 to Class 1.

HER2 mutation

It is recommended to increase the level of Trastuzumab to Class II in the back line treatment.

KRAS G12C

Small molecule inhibitors include Garsorasib (D-1553), IBI351, and JDQ443. In addition, the Fulzerasib has been approved for marketing by NMPA.

Non-squamous cell carcinoma

First-line PS=2 Partial Proposed Grade II addition of Atezolizumab, Dato-DXd Second-line Treatment Written Description Section.

Squamous carcinoma

First-line PS=2 Part II recommendation for the addition of Atezolizumab.

Version

Targeted Therapy Update Points

V1 ^[4]

EGFR Ex19del/L858R mutant NSCLC first-line treatment with the addition of combination chemotherapy with Osimertinib, and subsequent treatment with EGFR Ex19del/L858R mutant NSCLC that progressed after Osimertinib treatment as well as first-line treatment with Ex20ins mutant NSCLC with the addition of combination chemotherapy with Amivantamab (carboplatin+pemetrexed) and ROS1 rearrangement NSCLC treatment with the addition of Repotrectinib.

V2 ^[5]

Modification of ROS 1 rearrangement therapy: For asymptomatic patients and symptomatic patients with multiple systemic metastases, the addition of reotide is an option for subsequent therapy. Details of the treatment of Repotrectinib in patients with symptomatic brain metastases were adjusted to include Entrectinib as one of the previously administered drugs.

Extension of treatment with EGFR mutation: For patients carrying mutations of EGFR S768I, L861Q, and/or G719X, a new option has been added for the treatment of Amivantamab-vmjw with carboplatin and pemetrexed, which already provides full coverage in the main variants of EGFR.

V4 ^[7]

Molecular testing focused on molecular testing including EGFR, ALK, KRAS, ROS1, BRAF, NTRK1/2/3, METex14 skip, RET, and ERBB2(HER2) in all patients with advanced/metastatic non-squamous NSCLC (adenocarcinoma, large cell carcinoma) and non-specific NSCLC. Complete typing by repeat biopsy and/or plasma testing if there is insufficient tissue for full genotype testing; Simultaneous or sequential tissue and plasma testing is acceptable, but simultaneous testing shortens the time to test results and should be considered in an appropriate clinical setting. If one method is negative, i.e. there are no clear driver mutations, another complementary method may be chosen. If a clinically treatable gene mutation is found, it is reasonable to initiate treatment based on the identified gene mutation. If none of this is feasible, treatment will be guided based on the results available and, if the results are unclear, these patients will be considered driver-free.

V5 ^[8]

Adjuvant treatment after surgery for ALK-positive rearrangements: The addition of Alectinib as an adjuvant treatment option for patients with resectable ALK-positive NSCLC. Updates are based on the results of an ALINA study that showed a significant improvement in the 2-year disease-free survival (DFS) rate of patients with stage II/IIIA when compared to platinum-based chemotherapy.

Back-line treatment of HER2 overexpression in NSCLC: Adding T-Dx as a treatment option for patients with HER2 overexpression (IHC 3+) in NSCLC. Updated results based on three studies, DESTINY-PanTumor02, DESTINY-Lung01, and DESTINY-CRC02, show that trastuzumab is effective and safe.

V6 ^[9]

Recommendation for consolidation therapy with Osimertinib is recommended for patients with unresectable stage II/III NSCLC without disease progression after radical concurrent chemoradiotherapy who carry the eGFRCEXON19DEL or L858R mutation. Updates are based on results from the LAURA study, which showed that Osimertinib significantly prolonged the median progression-free survival (PFS) of patients compared with placebo.

V7 ^[10]

As a preferred treatment option for patients with NTRK fusion-positive NSCLC, the addition of Repotrectinib is indicated for patients with difficult surgical resection or who develop resistance to other NTRK inhibitors. Updated results based on a TRIDENT-1 study showing significant efficacy and tolerability of Repotrectinib in patients with NTRK fusion positive solid tumors. Repotrectinib was granted FDA accelerated approval on 13 June 2024 for use in patients with locally advanced or metastatic solid tumors for NTRK gene fusion.

V9 ^[12]

Treatment options for patients with EGFR, ROS1, and ALK mutations have been significantly optimized, in particular by providing a new first-line treatment option for patients with EGFR mutations with Amivantamab in combination with Lazertinib. The regimen is intended for patients who have detected either a missing EGFR exon19 or an L858R mutation, as well as for patients with newly discovered EGFR mutations during therapy. These updates are based on the results of the MARIPOSA study and highlight the options for individualized treatment in patients with EGFR mutations.

Version

Immunotherapy Update Points

V1 ^[4]

The regimen of Cemiplimab combined with chemotherapy becomes one of the first choices for patients with NSCLC with positive PD-L1 expression (≥50% or ≥1%-49%). The protocol recommendation or level of evidence for the combination of Tremelimumab with Durvalumab and chemotherapy has also been elevated in squamous cell carcinoma.

V8 ^[11]

The indications for perioperative immunotherapy have been updated with emphasis, especially on the use of Durvalumab. The newly-added protocol "the combination of bivalent platinum-based chemotherapy regimen with bivalent bivalirudin Durvalumab is applicable to patients with positive PD-L1 and no EGFR mutation or ALK rearrangement, and it is recommended to continue to use the bivalirudin Durvalumab as monotherapy after operation". Updated data are based on a Phase III AEGEAN study that showed significant long-term survival benefits of combination chemotherapy with Durvalumab for PD-L1 positive patients.

V10 ^[13]

The addition of Amivantamab in combination with chemotherapy (carboplatin and pemetrexed) as a first-line treatment of choice in patients with eX20 insertion mutations (Ex20ins) is indicated in patients with non-squamous NSCLC. This approval was based primarily on results from the PAPILLON study, which showed a significant improvement in median PFS in the combination group over the chemotherapy group alone, with an 18-month PFS rate of 31% and 3%, respectively.

V11 ^[14]

Nivolumab therapy with Nivolumab combined with platinum-containing double-agent chemotherapy was added, and postoperative Nivolumab adjuvant therapy was applied to patients with NSCLC in stage II-III B without complete resection of known EGFR mutation or ALK rearrangement. To update the results of a CheckMate 77T-based study evaluating the efficacy and safety of a peri-operative treatment model of "Nivolumab NIVO+ chemotherapy followed by surgery and adjuvant NIVO" in patients with resectable NSCLC in stages II-III b.