Lung Cancer

A Phase 3 Multicenter Double-blind Randomized Study Of Taletrectinib Versus Placebo In Patients With ROS1-fusion Positive Stage IB-IIIA Non-small Cell Lung Cancer Who Have Undergone Complete Tumor Resection (TRUST-IV)

MOA: Taletrectinib (AB-106 or DS-6051b) is a ROS1 tyrosine kinase inhibitor (TKI) effective against ROS1 and acquired resistance mutations

Key Eligibility Criteria:

• Histologically confirmed stage IB, II, or IIIA NSCLC that underwent locoregional curative surgery
• Documented ROS1 rearrangement in primary tumor tissue or liquid base sample (local)
• Co-mutations of EGFR or ALK fusion are excluded
• Postoperative radiation therapy is excluded; Radiotherapy in the neoadjuvant setting is allowed and must be completed at least 4 weeks prior to randomization
• Prior adjuvant anticancer therapy for treatment of NSCLC, other than standard postoperative platinum-based chemo, 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

A Phase 1/2 Study of Avutometinib in Combination with Sotorasib with or without Defactinib in Patients with KRAS G12C mutant Non-Small Cell Lung Cancer (NSCLC) (RAMP 203) (VS-6766-203)

Brief Summary: This study will assess the safety and efficacy of avutometinib (VS-6766) in combination with sotorasib with or without defactinib in patients with KRAS G12C Non-Small Cell Lung Cancer (NSCLC) in patients who have been exposed to prior G12C inhibitor and those who have not been exposed to prior G12C inhibitor.

Key Eligibility Criteria:

• Histologic/cytologic evidence of NSCLC, without histological evidence of a small cell component, that is metastatic (Stage 4)/locally advanced (Stage 3B-C)/unresectable)
• Known KRAS G12C mutation
• Either exposed or not exposed to a KRAS inhibitor to be included in Part A and not exposed to KRAS inhibitor to be included in Part B, Cohort 1
• Received at least 1 dose of a G12C inhibitor to be included in Part B, Cohort 2
• Must have received appropriate treatment with at least one prior systemic regimen, but no more than 2 prior regimens, for Stage 3B-C or 4 NSCLC
• Systemic anti-cancer therapy within 4 weeks of the first dose of study therapy excluded
• History of prior malignancy, with the exception of curatively treated malignancies excluded
• History of treatment with a direct and specific inhibitor of MEK excluded

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 Phase 2, Open-Label, Randomized, Global Study of Two Telisotuzumab Vedotin Regimens in Subjects With Previously Treated c-Met Overexpressing, EGFR Wildtype, Locally Advanced/Metastatic Non-Squamous Non-Small Cell Lung Cancer

Brief Summary: The purpose of this study is to assess how safe telisotuzumab vedotin is in adult participants with NSCLC. Change in disease activity and adverse events will be assessed. Participants will be randomly assigned a treatment of telisotuzumab vedotin in 1 of 3 arms at an 1:1:1 ratio.

Key Eligibility Criteria:

• Must have c-Met overexpressing non-small cell lung cancer (NSCLC)
• Must have histologically or cytologically documented NSCLC that is locally advanced or metastatic
• Must have a known epidermal growth factor receptor (EGFR) activating mutation status
• Must have received no more than 1 line of prior systemic cytotoxic chemotherapy in the locally advanced or metastatic setting
• Must have progressed on at least 1 line of prior therapy for locally advanced/metastatic NSCLC
• Adenosquamous or neuroendocrine histology, or sarcomatoid features excluded
• Actionable EGFR activating mutations excluded

A Phase III, Two-Arm, Parallel, Randomized, Multi-Center,Open-Label, Global Study to Determine the Efficacy of Volrustomig (MEDI5752) Plus Chemotherapy Versus Pembrolizumab Plus Chemotherapy for First-Line Treatment of Patients with Metastatic Non-Small Cell Lung Cancer (mNSCLC) (eVOLVE-Lung02) (D798AC00001)

MOA: Volrustomig is a bispecific antibody targeting PD-1 and CTLA-4 designed to provide improved safety and efficacy over the combination of antiPD-1 and anti-CTLA4 monotherapies.

Key Eligibility Criteria:

• Treatment naïve patients with squamous and nonsquamous mNSCLC
• PD-L1 < 50% must be assessed using central laboratory with tumor tissue provided during screening phase.
• Tumors must lack EGFR mutations and ALK and ROS1 rearrangements.
• No actionable genomic alterations for which there are locally approved 1L targeted therapies.

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 1/2 Study to Assess BDTX-1535, an Oral EGFR Inhibitor, in Patients with Glioblastoma or Non-Small Cell Lung Cancer (BDTX-1535-101)

Brief Summary: BDTX-1535-101 is an open-label, Phase 1 dose escalation and Phase 2 multiple cohort study designed to evaluate the safety, pharmacokinetics (PK), optimal dosage, central nervous system (CNS) activity, and antitumor activity of silevertinib (BDTX-1535).

Key Eligibility Criteria:

• Confirmed NSCLC, without small cell lung cancer transformation with or without brain metastases.
• Measurable disease by RECIST 1.1 criteria.
• Disease progression following or intolerance of standard of care (excluding patients in the treatment-naïve non-classical driver cohort)
• Identification of one (or more) EGFR mutations by Next Generation Sequencing (NGS) as determined by a local assay performed in a validated laboratory in the absence of other known resistance mutations
• Known resistant mutations in tumor tissue or by liquid biopsy excluded
• Received more than 1 EGFR TKI therapy (ie, erlotinib or gefitinib) for the treatment of metastatic or recurrent EGFR NSCLC excluded

***REFERRAL ONLY***A Global, Phase 3, Randomized, Multicenter, Open-Label Study to Investigate the Efficacy and Safety of Furmonertinib Compared to Platinum-Based Chemotherapy as First-Line Treatment for Patients with Locally Advanced or Metastatic Non-Small Cell Lung Cancer with Epidermal Growth Factor Receptor Exon 20 Insertion Mutations

Brief Summary: This is a global, Phase 3, randomized, multicenter, open-label study evaluating the efficacy and safety of furmonertinib at 2 dose levels (160 mg and 240 mg) compared to platinum-based chemotherapy in previously untreated patients with locally advanced or metastatic nonsquamous NSCLC with EGFR exon 20 insertion mutations.

Key Eligibility Criteria:

• Histologically or cytologically documented, locally advanced or metastatic non-squamous Non-Small Cell Lung Cancer (NSCLC) not amenable to curative surgery or radiotherapy
• Documented results of the presence of an Epidermal Growth Factor Receptor (EGFR) exon 20 insertion mutation
• No prior systemic anticancer therapy regimens received for locally advanced or metastatic NSCLC including prior treatment with any EGFR -targeting agents
• Patients who have received prior neo-adjuvant and/or adjuvant chemotherapy, immunotherapy, or chemo radiotherapy for non-metastatic disease (excluding EGFR-TKIs) must have experienced a treatment free interval of at least 12 months

A Phase 2 Trial of Adagrasib Monotherapy and in Combination with Pembrolizumab and a Phase 3 Trial of Adagrasib in Combination with Pembrolizumab versus Pembrolizumab in Patients with Advanced Non-Small Cell Lung Cancer with KRAS G12C Mutation (849-007)

Brief Summary: The Phase 2 portion of this study evaluates the efficacy and safety of MRTX849 monotherapy and in combination with pembrolizumab in cohorts of patients with advanced NSCLC with KRAS G12C mutation and any PD-L1 TPS and who are candidates for first-line treatment. The Phase 3 portion of the study compares the efficacy of adagrasib in combination with pembrolizumab versus pembrolizumab in patients with unresectable, locally advanced or metastatic squamous or nonsquamous NSCLC with KRAS G12C mutation and PD-L1 TPS >=50% and who are candidates for first line treatment.

Key Eligibility Criteria:

• Histologically confirmed diagnosis of unresectable or metastatic NSCLC with KRAS G12C mutation and any PD-L1 TPS
• Histologically confirmed diagnosis of unresectable or metastatic squamous or nonsquamous NSCLC with KRAS G12C mutation and PD-L1 TPS >=50%
• Presence of evaluable or measurable disease per RECIST
• Prior systemic treatment for locally advanced or metastatic NSCLC including chemotherapy, immune checkpoint inhibitor therapy, or a therapy targeting KRAS G12C mutation excluded

A phase 3 randomized, open-label, multicenter study evaluating the efficacy and safety of divarasib versus sotorasib or adagrasib in patients with previously treated KRAS G12C-positive advanced or metastatic Non-Small Cell Lung Cancer (BO45217)

MOA: Divarasib (GDC-6036), Sotorasib (AMG 510) and adagrasib (MRTX849) are KRAS G12C selective inhibitor.

Key Eligibility Criteria:

• Metastatic or locally advanced NSCLC not amenable to
  treatment with surgical resection or combined chemoradiation
• Progression during or after treatment with at least one prior
  systemic therapy but no more than three lines in the advanced
  or metastatic setting
  • Prior systemic treatment must include a platinum-based doublet
    chemotherapy regimen and a PD-L1/PD-1 inhibitor
  • Systemic therapy done <6 months between the last dose and the
    date or recurrence qualify as prior systemic therapy
• KRAS G12C + result by central or CLIA-certified lab in tumor
  tissue or blood
• KEAP1 mutation status by designated NGS from certified lab
• No known and untreated or active CNS metastases

Beamion LUNG-2: A Phase III, open-label, randomized, active-controlled, multi-centre trial evaluating orally administered zongertinib (BI 1810631) compared with standard of care as first-line treatment in patients with unresectable, locally advanced or metastatic non-squamous non-small cell lung cancer harbouring HER2 tyrosine kinase domain mutations

Brief Summary: The purpose of this study is to find out whether Zongertinib (BI 1810631) can slow down the worsening of advanced non-small cell lung cancer better than the standard treatment available. Zongertinib may slow cancer cell growth by inhibiting HER2. This would prolong cancer re-occurrence and increase survival.

Key Eligibility Criteria:

• Histologically or cytologically confirmed diagnosis of an advanced and/or metastatic non-squamous Non-small cell lung cancer (NSCLC)
• Documented Human epidermal growth factor receptor 2 (HER2) mutation in the Tyrosine kinase domain (TKD) as per local lab results
• Patients who have not received any systemic treatment for unresectable, locally advanced or metastatic disease and are not eligible for curative therapy
• Presence of at least one measurable lesion according to Response evaluation criteria in solid tumors (RECIST) 1.1
• Tumors with targetable alterations with approved available therapy excluded

A Phase 2 Study of EIK1001 in Combination with Pembrolizumab and Chemotherapy in Patients with Stage 4 Non-Small Cell Lung Cancer (EIK1001-005)

MOA: EIK1001 is a Toll-like receptor (TLR)7/8 dual agonist.

Key Eligibility Criteria:

• Histologically or cytologically confirmed Stage 4 squamous or nonsquamous NSCLC and be considered for standard therapy with pembrolizumab and chemotherapy
• Patient must have confirmation that mutation-directed therapy is not indicated
• Patients that received prior systemic treatment for advanced/metastatic NSCLC are excluded
• Patients that received radiation therapy to the lung that is > 30 Gy within 6 months of the first dose of study drug administration excluded

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 Phase 1/2 Study of Avutometinib (VS-6766) in Combination with Sotorasib in Patients with KRAS G12C mutant Non-Small Cell Lung Cancer (NSCLC) (RAMP 203) (VS-6766-203)

Brief Summary: This study will assess the safety and efficacy of avutometinib (VS-6766) in combination with sotorasib with or without defactinib in patients with KRAS G12C Non-Small Cell Lung Cancer (NSCLC) in patients who have been exposed to prior G12C inhibitor and those who have not been exposed to prior G12C inhibitor.

Key Eligibility Criteria:

• Histologic or cytologic evidence of NSCLC
• Known KRAS G12C mutation
• Either exposed or not exposed to a KRAS inhibitor to be included in Part A (avutometinib + sotorasib + defactinib) and not exposed to KRAS inhibitor to be included in Part B (avutometinib + sotorasib + defactinib), Cohort 1
• Received at least 1 dose of a G12C inhibitor to be included in Part B, Cohort 2 (avutometinib + sotorasib + defactinib)
• Must have received appropriate treatment with at least one prior systemic regimen, but no more than 2 prior regimens, for Stage 3B-C or 4 NSCLC
• Systemic anti-cancer therapy within 4 weeks of the first dose of study therapy excluded
• History of treatment with a direct and specific inhibitor of MEK excluded
• Exposure to strong CYP3A4 inhibitors or inducers within 14 days prior to the first dose and during the course of therapy excluded

A PHASE I-III, MULTICENTER STUDY EVALUATING THE EFFICACY AND SAFETY OF MULTIPLE THERAPIES IN COHORTS OF PATIENTS SELECTED ACCORDING TO BIOMARKER STATUS, WITH LOCALLY ADVANCED, UNRESECTABLE, STAGE III NON-SMALL CELL LUNG CANCER

Brief Summary: This study will evaluate the efficacy and safety of multiple therapies in participants with locally advanced, unresectable, Stage III NSCLC with eligible biomarker status as determined by Version 8 of the American Joint Committee on Cancer/Union for International Cancer Control NSCLC staging system.

Key Eligibility Criteria:

• Histologically/cytologically documented locally advanced, unresectable Stage III NSCLC of either squamous/non-squamous histology
• Prior receipt of at least two prior cycles of platinum-based chemotherapy given concurrently with radiotherapy (cCRT); or at least two prior cycles of platinum-based chemotherapy given prior to radiotherapy (sCRT)
• No disease progression during or following platinum-based cCRT or sCRT
• Any history of previous NSCLC and/or any history of prior treatment for NSCLC excluded
• Any evidence of Stage IV disease excluded
• NSCLC known to have a known or likely oncogenic-driver mutation in the EGFR gene excluded

A Placebo-controlled Double-Blinded Randomized Phase 3 Study of Adjuvant Selpercatinib following Definitive Locoregional Treatment in Participants with Stage IB-IIIA RET fusion-Positive NSCLC (LIBRETTO-432) (J2G-MC-JZJX)

Brief Summary: The purpose of this study is to see if the study drug, Selpercatinib, compared to placebo is effective and safe in delaying cancer return in participants with early-stage non-small cell lung cancer (NSCLC), who have already had surgery or radiation. Participants who are assigned to placebo and stop the study drug because their disease comes back or gets worse have the option to potentially crossover to Selpercatinib. Participation could last up to three years.

Key Eligibility Criteria:

• Must have histologically confirmed Stage IB, II, or IIIA NSCLC
• Must have an activating RET gene fusion in tumor 
• Must have received definitive locoregional therapy with curative intent (surgery or radiotherapy) for Stage IB, II, or IIIA NSCLC
  • Must have undergone the available anti-cancer therapy (including chemotherapy or durvalumab) or not be suitable for it, based on the investigator's discretion
• Additional oncogenic drivers in NSCLC, if known excluded
• Evidence of small cell lung cancer excluded
• Clinical or radiologic evidence of disease recurrence or progression following definitive therapy excluded

A Randomized Phase 3 Study of Datopotamab Deruxtecan (Dato-DXd) and Pembrolizumab, with or Without Platinum Chemotherapy, in Subjects with No Prior Therapy for Advanced or Metastatic PD-L1 TPS <50% Non-squamous Non-small Cell Lung Cancer Without Actionable Genomic Alterations (TROPION-Lung07) (DS1062-A-U303)

MOA: Dato-DXd: an ADC that comprises a recombinant humanized anti-TROP2 IgG1 mAb that is covalently conjugated to a drug-linker, via thioether bonds Pembrolizumab: humanized IgG4 mAb with the high specificity of binding to the PD-1 receptor

Key Eligibility Criteria:

• Histologically documented advanced or metastatic non-squamous NSCLC
• No prior systemic therapy
• Able to provide a formalin-fixed tumor tissue sample for the measurement of TROP2 protein expression and for the assessment of other exploratory biomarkers
• Has documented negative test results for EGFR, ALK, and ROS1 actionable genomic alterations AGAs based on analysis of tumor tissue
• Measurable disease based on local imaging assessment using RECIST v1.1

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&gt;=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