Lung Cancer

A Phase 3 Study of the Selective Anaplastic Lymphoma Kinase (ALK) Inhibitor NVL-655 Compared to Alectinib in First-Line Treatment of Patients With ALK-Positive Advanced Non-Small Cell Lung Cancer (ALKAZAR) (NVL-655-04)

MOA: NVL-655 is an ALK TKI, designed for broader coverage of ALK resistance mutations, activity in the CNS, and selectivity over TRKB.

Key Eligibility Criteria:

• Histologically or cytologically confirmed LA (not amenable for multimodality treatment) or metastatic NSCLC
• Documented ALK rearrangement in tissue or blood (circulating tumor DNA [ctDNA]) – Local testing
  • Pre-treatment tumor tissue must be submitted for central analysis during screening
• No prior systemic anticancer tx for NSCLC, including but not limited to molecularly targeted agents, angiogenesis inhibitors, immunotherapy, or chemotherapy
  • Adj/neoadjuvant chemotherapy is allowed if completed ≥12 months prior to randomization.
  • Prior ALK TKI as adj/neoadj tx is not permitted
• No other known oncogenic driver alterations other than ALK
• Measurable disease by RECIST 1.1

A Phase III, Randomised, Open-Label, Multicentre Study of Datopotamab Deruxtecan or Docetaxel in Previously Treated TROP2-positive Advanced or Metastatic Non-squamous Non-Small Cell Lung Cancer Without Actionable Genomic Alterations (TROPION-Lung17, D763QC00001)

MOA: Datopotamab Deruxtecan (Dato-DXd) is an ADC targeting TROP2 containing a topoisomerase I inhibitor payload

Key Eligibility Criteria:

• Documented Stage IIIB, IIIC, or Stage IV non-squamous NSCLC without AGA at the time of randomization
  • Must have negative test results for EGFR, ALK, ROS1 genomic alterations
  • No known tumor genomic alterations in NTRK, BRAF, RET, MET exon 14 skipping, KRAS G12C, HER2 or any AGA with approved targeted tx
  • KRAS mutations, with exception of G12C, are eligible
• Radiographic PD on/after most recent tx for adv/met NSCLC
• 1-2 prior lines of tx with plt-based chemo + anti-PD-(L)1 combined or sequentially (in any order)
  • Prior tx with docetaxel excluded
  • Prior tx with any anti-TROP2 agent excluded
• Must provide FFPE tumor sample for assessment of TROP2
• Spinal cord compression or brain metastases excluded
  • If asymptomatic, stable, and without corticosteroids or anticonvulsants for at least 7 days prior to randomization are eligible
• At least 1 measurable lesion per RECIST v1.1

A Randomized, Open-Label, Phase 3 Study of ZL-1310, a DLL3 Antibody-Drug Conjugate (ADC), Compared to Investigator’s Choice Therapy in Participants with Relapsed Small Cell Lung Cancer

MOA: ZL-1310 is an ADC that targets DLL3 and contains a topoisomerase I inhibitor payload

Key Eligibility Criteria:

• Confirmed diagnosis of SCLC
• Archival tumor tissue or fresh tumor tissue must be submitted at screening. DLL3 expression will be assessed retrospectively.
• Must have received only 1L plt-based chemo and had documented disease progression during/after most recent systemic tx
  • Prior 1L systemic tx should be plt-base chemo with an anti-PD(L)1 agent
    • Maintenance tx with anti-PD-(L1)/lurbinectedin/tarlatamab does not count as a separate line of tx
    • Plt-base chemo for limited-stage SCLC is considered one line of tx
  • 2L systemic tx is not allowed, except for tarlatamab
• Measurable disease according to RECIST v1.1
• Prior tx with ADC containing any topoisomerase I inhibitor payload are excluded
• Treated and stable CNS metastases are eligible (parenchimal).
  • Metastasis to leptomeninges are excluded
• Untreated and asymptomatic CNS metastases are eligible but must not require steroids and/or anti-convulsants, nor local tx

An Interventional Phase 3, Double-Blind, Randomized Study to Evaluate Efficacy and Safety of PF-08634404 in Combination With Chemotherapy Versus Pembrolizumab in Combination With Chemotherapy in Adult Participants With Locally Advanced or Metastatic Non-Small Cell Lung Cancer

MOA: F-08634404 is a PD-1xVEGF bispecific antibody.

Key Eligibility Criteria:

• LA (Stage IIIB/C) or met (Stage IV) squamous or non-squamous NSCLC not eligible for curative surgery and/or chemoradiotherapy
• PD-L1 status available based on local SoC testing results
• Measurable disease by RECIST v1.1
• Participants with known AGAs with available front-line tx are excluded
  • Pts with non-squamous NSCLC must have documented negative results for EGFR, ALK, and ROS1 AGAs
• Known active CNS or leptomeningeal metastases are excluded
• Pts with clinically significant risk of hemorrhage or fistula are excluded
• Prior systemic anti-tumor therapy, including anti-PD-(L)1 tx for LA/met NSCLC are excluded
  • (Neo)adjuvant anti-PD-(L)1 allowed if PD occurred ≥9 months after the last dose
  • Other (neo)adjuvant or definitive therapy is allowed if PD occurred ≥6 months after the last dose.

A randomized, Phase 3, open-label study to evaluate PF-08046054/SGN-PDL1V vs Docetaxel in adult participants with previously-treated programmed cell death ligand (PD-L1) positive non-small cell lung cancer (NSCLC)

MOA: F-08046054/SGN-PDL1V is an anti-PD-L1 ADC with a MMAE payload

Key Eligibility Criteria:

• Histologically or cytologically documented unresectable Stage IIIB, IIIC, IV NSCLC not eligible for definitive chemoradiotherapy.
  • Tumors with small cell and neuroendocrine histology components are excluded
• PD-L1 expression on ≥1% of tumor cells based on local IHC testing
• Participants who have NSCLC with known AGAs are permitted
• Archival or fresh tissue required for biomarker analysis.
• Pts must have received the following therapies and progressed during or relapsed after receiving their most recent prior therapy:
  • Pts with no known AGA: must have received chemo + anti-PD-L1 mAb
  • Pts with known AGAs: must have received at least 1 approved targeted therapy, chemotherapy, and an anti-PD-L1 mAb.
• Brain metastases are excluded unless asymptomatic, stable, and not requiring steroids or anticonvulsants for at least 4 weeks prior to start of study intervention
• Prior tx with an anti-PD-L1 agent within 5 half-lives are excluded
• Prior receipt of an MMAE-containing agent or docetaxel are excluded

A Phase 3 Randomized Double-blind Study of Adjuvant Pembrolizumab With or Without V940 in Participants With Resectable Stage II to IIIB (N2) NSCLC not Achieving pCR After Receiving Neoadjuvant Pembrolizumab With Platinum-based Doublet Chemotherapy (INTerpath-009) (V940-009)

MOA: V940 is a lipid encapsulated mRNA based Individualized Neoantigen Therapy (INT) encoding neoantigens to induce specific T cells and associated anti-tumor responses (both CD8 and CD4)

Key Eligibility Criteria:

• Histologically/cytologically confirmed diagnosis of resectable Stage II, IIIA, or IIIB (N2) NSCLC
• No prior therapy (except pts enrolled after the neoadjuvant treatment and surgery)
• Pt who received up to 4 cycles of pembrolizumab and platinum-doublet chemotherapy, followed by R0 or R1 lobectomy or pneumonectomy, may enroll if all eligibility criteria are met
• No prior anti-PD(L)1 or with another stimulatory/coinhibitory TCR or cancer vaccine, including another INT
• Chemotherapy and pembrolizumab followed by surgery will be eligible
• Documentation of absence of tumor-activating EGFR mutations and ALK gene rearrangements

Molecularly Informed Lung Cancer Treatment in a Community Cancer Network: A Pragmatic Consortium and Longitudinal Prospective Study (MYLUNG Program: Part 3) Order-Set-Go: Increasing Biomarker Testing Rates in Patients with Non-small-cell Lung Cancer Through Use of Clinical Decision Support Tools (MYLUNG/23329/LUN 576)

Brief Summary: This longitudinal study looks to quantify the testing timeline, operational barriers, and outcomes of biomarker-guided therapy in a large, community-based, and largely unselected patient population with early stage and advanced stage, treatment-naive non-small cell lung cancer, whether squamous or non-squamous.

Key Eligibility Criteria:

• Adult subjects (18 years and older) with newly diagnosed early stage, locally advanced or metastatic non-small cell lung cancer
• Must be eligible for systemic therapy based on the treating provider's assessment. If systemic therapy was recommended and documented by the treating provider but the patient declined, they can still be eligible for the study
• Subjects who developed locally advanced or metastatic disease after receiving adjuvant or neoadjuvant therapy are eligible if the adjuvant/neoadjuvant therapy was completed at least 12 months prior to the development of locally advanced or metastatic disease
• Stage IA at the time of enrollment excluded
• Subjects with small cell lung cancer excluded
• Subjects with Unknown primary tumor origin excluded

A Phase 2b, Open-Label, Two-cohort Study of Subcutaneous Amivantamab in Combination with Lazertinib as First-Line Treatment, or Subcutaneous Amivantamab in Combination with Platinum-Based Chemotherapy as Second-line Treatment, for Common EGFR-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer (COPERNICUS) (61186372NSC2012)

MOA: Subcutaneous amivantamab is a bispecific ab against EGF and cMET receptors, that is co-formulated with rHuPH20. Lazertinib is a 3rd generation EGFR TKI.

Key Eligibility Criteria:

• Histologically or cytologically confirmed LA or metastatic NSCLC
• EGFR mutation must be an Ex19del or Ex21 L858R substitution (local). Liquid or tissue biopsy acceptable
• At least 1 measurable lesion, according to RECIST v1.1, not irradiated
• Cohort 1: No prior systemic therapy for adv/met NSCLC or any targeted tx for early disease stage
• 1 cycle of plt chemo is permitted prior to the first dose of treatment while awaiting liquid or tissue biopsy results
• Asymptomatic or previously treated and stable brain metastases are eligible

A Global Pivotal Study in Participants with KRAS G12C-Mutant, Locally Advanced or Metastatic Non-Small Cell Lung Cancer Comparing First-Line Treatment of LY3537982 and Pembrolizumab vs Placebo and Pembrolizumab in those with PD-L1 expression >= 50% or LY3537982 and Pembrolizumab, Pemetrexed, Platinum vs Placebo and Pembrolizumab, Pemetrexed, Platinum regardless of PD-L1 Expression (J3M-MC-JZQB)

MOA: LY3537982 is an orally bioavailable small molecule inhibitor of the KRASG12C protein

Key Eligibility Criteria:

• Locally advanced or metastatic (Stage IIIB-IIIC or Stage IV) NSCLC
• Previously untreated, not suitable for curative intent surgery
• Prior neoadj/adjuvant or consolidation therapy will be allowed provided treatment was completed 6 months prior to study entry
• 1 cycle of SOC prior to study enrollment will be allowed for cases where immediate therapy is clinically indicated, as follows:
  • Part A: single cycle of pembrolizumab pembrolizumab, or pembrolizumab monotherapy
  • Part B: single cycle of either pemetrexed-platinum with or without
• KRASG12C mutation and PD-L1 expression determined in tumor tissue or blood (local testing) are required
• No known targetable mutation or alteration in genes such as EGFR, ALK, BRAF (V600E), HER2, MET (exon 14), ROS1, RET, or NTRK1/2/3 (testing is not required).
• No active CNS metastases and/or carcinomatous meningitis

A Randomized, Open-label, Phase 3 Trial of Dato-DXd Plus Pembrolizumab vs Pembrolizumab Alone in Treatment-naive Subjects with Advanced or Metastatic PD-L1 High (TPS>=50%) Non-small Cell Lung Cancer Without Actionable Genomic Alterations (TROPION-Lung08)(Dato-DXd Plus Pembrolizumab vs Pembrolizumab Alone in the First-line Treatment of Subjects with Advanced or Metastatic NSCLC Without Actionable Genomic Alterations)(DS1062-A-U304)

Brief Summary: This study is designed to assess the efficacy and safety of datopotamab deruxtecan (Dato-DXd) in combination with pembrolizumab versus pembrolizumab alone in participants with advanced or metastatic non-small cell lung cancer (NSCLC) of non-squamous histology.

Key Eligibility Criteria:

• Histologically documented Stage IIIB/IIIC NSCLC not candidates for surgical resection/definitive chemoradiation, or Stage IV NSCLC disease
• Documented negative test results for EGFR/ALK/ROS1 actionable genomic alterations
• No known actionable genomic alterations in NTRK/BRAF/RET/MET/other actionable driver kinases
• Tumor has high PD-L1 expression (TPS ≥50%)
• Received prior systemic treatment for advanced/metastatic NSCLC excluded
• Received prior treatment in any of adjuvant/neoadjuvant setting excluded

A Phase 1/2 Open-Label, Dose-Escalation and Clinical Response Study of Quaratusugene Ozeplasmid in Combination with Osimertinib in Patients with Advanced, EGFR-Mutant, Metastatic Non-Small Cell Lung Cancer who have Progressed after Treatment with Osimertinib (ONC-003)

MOA: Quaratusugene ozeplasmid (REQORSA™, GPX-001) has been shown to modulate the immune system

Key Eligibility Criteria:

• Histologically/cytologically documented NSCLC
• Stage III/IV NSCLC or recurrent NSCLC that is not potentially curable by radiotherapy/surgery whether or not patient has received prior chemotherapy
• EGFR mutation-positive as detected by an FDA-approved test
• Achieved clinical response to osimertinib for ≥4 months
• Radiological progression on/after treatment with osimertinib with asymptomatic/symptomatic disease with limited metastasis
• ECOG PS of 0 or 1
• Unable to tolerate osimertinib treatment excluded
• Progressing patients who are symptomatic and have >5 metastasis excluded
• Prior gene therapy excluded