Clinical Research Directory

A Clinical Study to Assess the Efficacy of Adjuvant Immunotherapy With Cemiplimab in Patients With Surgically Removed Non-small Cell Lung Cancer Who Have Not Received Prior Chemotherapy

ARCH is a randomised, stratified, multicentre, phase III trial. Protocol treatment consists of cemiplimab, 350 mg i.v., every 3 weeks, for 4 cycles, followed by 700 mg i.v., every 6 weeks for 6 cycles or until relapse or unacceptable toxicities, whichever occurs first. The primary objective of the study is to determine the efficacy of adjuvant cemiplimab, as measured by disease-free survival, in patients without prior adjuvant platinum-based chemotherapy, compared to observation without adjuvant treatment. The primary objective will be assessed in patients with tumours with centrally confirmed PD-L1 expression of ≥1%.

MRD-Guided Aumolertinib-Based Adjuvant Therapy for Resected EGFR-Mutant NSCLC

Despite complete (R0) resection, patients with EGFR-mutant stage IIA-IIIB non-small cell lung cancer (NSCLC) still face a substantial risk of postoperative recurrence. Although adjuvant EGFR tyrosine kinase inhibitors have improved disease-free survival, conventional fixed-duration adjuvant therapy is applied uniformly to all patients and does not distinguish those who genuinely require treatment from those who could be safely spared. Circulating tumor DNA (ctDNA) profiling enables minimal residual disease (MRD) detection that is both earlier and more accurate than imaging, and has therefore emerged as a promising tool for individualizing postoperative adjuvant therapy. This prospective, real-world, interventional study will enroll 50 patients with resected (R0), EGFR 19del or L858R mutant, stage IIA-IIIB non-squamous NSCLC. For three years after surgery, adjuvant treatment is dynamically guided by serial MRD testing performed 3-10 days and 4 weeks (±7 days) after surgery and every 3-6 months thereafter. Patients with a positive MRD result at either of the first two time points receive aumolertinib-based adjuvant therapy, with the regimen determined by the mutations detected in blood: aumolertinib monotherapy (110 mg once daily) when only the EGFR mutation is detected, or aumolertinib combined with chemotherapy (pemetrexed plus carboplatin for four cycles, followed by pemetrexed maintenance) when co-mutations are detected. Patients whose MRD remains negative undergo observation with regular ctDNA monitoring; if MRD turns positive or imaging progression occurs, aumolertinib-based adjuvant therapy is initiated according to the same rules. Treatment is discontinued once MRD becomes undetectable; patients with persistently negative MRD over three years receive no aumolertinib. After three years, subsequent treatment is at the investigator's discretion. The primary endpoint is the 2-year disease-free survival (DFS) rate, defined as the proportion of patients remaining free from recurrence or death for at least 24 months after surgery. Secondary endpoints include the 2-, 3-, and 5-year overall survival rates, 3-year total treatment cost, incremental cost-effectiveness ratio, rate of timely postoperative recurrence diagnosis, and cumulative duration of aumolertinib treatment; exploratory analyses will assess the association between ctDNA/MRD molecular features and clinical efficacy. This study aims to establish a dynamic MRD-guided precision adjuvant strategy that avoids overtreatment while improving outcomes in resected EGFR-mutant NSCLC.

Concurrent Immunotherapy and Systemic Therapy With Stereotactic Body Radiation Therapy (SBRT) for Stage IV Cancers (COINSSS IV)

This is a Phase II clinical study for people with stage IV cancer. The study will evaluate the use of stereotactic body radiation therapy (SBRT), a type of focused radiation treatment, together with immunotherapy-based treatment. SRBT will be used to treat multiple areas of cancer that have spread to other parts of the body. The study will evaluate whether this treatment approach can be safely given while patients continue their planned cancer treatment and may help control their cancer.

TCR1188-ABC Cells in KRAS-mutated Cancers

This is a Phase I, open-label dose finding study to assess the safety, manufacturing feasibility, and preliminary efficacy of TCR1188-ABC cells in patients with KRAS-mutated cancers. Initially, patients with KRAS G12V mutation positive metastatic pancreatic adenocarcinoma, cholangiocarcinoma, colorectal cancer, or non-small cell lung cancer (NSCLC) will be targeted for participation. Up to 4 total dose levels will be evaluated using a 3+3 dose escalation design.

A Phase 2 Study of VS-7375 in Patients With KRAS G12D-Mutated Non-Small Cell Lung Cancer

This study will assess the safety and efficacy of VS-7375 alone and in combination with cetuximab in patients with metastatic KRAS G12D - mutated Non-Small Cell Lung Cancer

Evaluation of a Cancer Lysate Vaccine and Montanide (Registered Trademark) ISA-51 VG With or Without the IL-15 Super-Agonist N-803 as Adjuvant Therapy for PD-L1 Negative Non-Small Cell Lung Cancer

Background: Surgery is the primary treatment for non-small cell lung cancer (NSCLC) that is diagnosed in its earlier stages. But the tumors often return. Radiation and chemotherapy can improve survival in some people who have had surgery for NSCLC, but these treatments also cause serious side effects. A new approach, called immunotherapy, may be a better way to stop NSCLC tumors from coming back. Objective: To test a new treatment (H1299 lung cancer cell vaccine combined with the drug N-803) in people who received surgery for NSCLC. Eligibility: Adults aged 18 years or older with no sign of disease after surgery for NSCLC. Design: Participants will be screened. They will have a physical exam with blood tests. They will have tests of their heart and lung function. They will have imaging scans. Study treatment will be given in 28-day cycles. Participants will visit the clinic on the first day of each cycle. They will receive 2 treatments at each visit: The study vaccine is given as 2-4 small shots under the skin of the thigh or arm. N-803 is given as a shot under the skin of the abdomen. Treatment will continue for 6 cycles. Blood tests and imaging scans will be repeated throughout the study. Participants will have a blood test 1 month after receiving the 6th vaccine. Some participants may then resume taking N-803; they may also receive 2 more vaccinations at 3 and 6 months after their previous treatment. Follow-up visits will continue for up to 5 years.

Safety and Efficacy of BA1302 in Patients With Advanced Solid Tumors

This is a first-in-human (FIH), multicenter, open-label Phase I study to evaluate the safety, tolerability, PK profile, immunogenicity, and preliminary efficacy of BA1302 in patients with advanced solid malignancies. The study includes a dose-escalation phase (Part A) and a dose-expansion phase (Part B).

Cabozantinib in Patients With RET Fusion-Positive Advanced Non-Small Cell Lung Cancer and Those With Other Genotypes: ROS1 or NTRK Fusions or Increased MET or AXL Activity

The purpose of this phase II study is to find out what effects cabozantinib (XL184) has, good and/or bad, in patients whose tumors one of the following gene changes RET, ROS1, or NTRK fusion, or increased MET or AXL activity. A phase II study looks at how effective a medication is at treating a specific type of cancer and collects information on the side effects of the study treatment. RET, ROS1, or NTRK fusion or increased MET or AXL activity gene leads to lung cancer cell growth. Cabozantinib is an oral medicine that inhibits of RET, ROS1, NTRK, MET, and AXL. In addition, this drug interferes with other cell pathways that also cause cancer cells to grow, form new blood vessels, and spread to other organs of the body. The goal of using cabozantinib is to shrink the cancer and to prevent it from growing Cabozantinib has been studied and shown to cause cancer shrinkage in other cancers such as medullary thyroid cancer and prostate cancer. We thus have a good idea of what side-effects it causes and can anticipate them.

An Expanded Access Program to Provide Divarasib to Participants With Previously Treated KRAS G12c-Positive Advanced or Metastatic Non-Small Cell Lung Cancer

The purpose of this expanded access program (EAP) is to provide early access to divarasib to participants with KRAS G12C-positive (KRAS G12C+) advanced or metastatic non-small cell lung cancer (NSCLC), prior to divarasib becoming commercially available in the United States.

Biomarker Testing to Predict Radiation-Related Heart Disease in Lung Cancer Patients

The study will measure serum Pro-N-Cadherin and NT-proBNP (pro B-type natriuretic peptide) levels in adults with non-small cell lung cancer receiving hypofractionated radiation therapy and evaluate whether these biomarkers correlate with radiation dose to the heart, cardiac dysfunction, and adverse cardiac events. Participants will undergo blood collection and echocardiography over a two-year follow-up period.

Phase I-II, FIH, TROP2 ADC, Advanced Unresectable/Metastatic Solid Tumors, Refractory to Standard Therapies (KL264-01)

A Phase I-II, First-in-Human Study of SKB264 (Sac-TMT; MK-2870) in Patients with Locally Advanced Unresectable/Metastatic Solid Tumors who are refractory to Available Standard Therapies. Patient must have historically documented, incurable, locally advanced or metastatic cancer that are refractory to standard therapies of one of the following types: 1. Triple negative breast cancer 2. Epithelial ovarian cancer 3. Non-small cell lung cancer 4. Gastric adenocarcinoma/Gastroesophageal junction adenocarcinoma 5. Small cell lung cancer 6. HR+/ HER2-breast cancer 7. Head and neck squamous cell carcinoma 8. Endometrial carcinoma 9. Urothelial carcinoma 10. Cervical cancer

CHOICE:Decision Factor of EGFR-TKI in Chinese IV NSCLC

This non-interventional, cross-sectional study aims to investigate treatment preferences from a sample of physicians and patients with experience of 1L EGFR-TKI for stage IV NSCLC by administering a survey, which primarily includes a DCE approach.

Phase I Study of [177Lu]Lu-DFC413 in Patients With Solid Tumors

The purpose of this study is to evaluate the safety, tolerability, dosimetry and preliminary efficacy of \[177Lu\]Lu-DFC413 and safety and imaging properties of \[68Ga\]Ga-NNS309 in patients aged ≥ 18 years with solid tumors

Study of Izalontamab Brengitecan (BMS-986507) Versus Platinum-Pemetrexed for EGFR-mutated Non-small Cell Lung Cancer After Failure of EGFR TKI Therapy (IZABRIGHT-Lung01)

A Study of Izalontamab Brengitecan (BMS-986507) versus Platinum-Pemetrexed for EGFR-mutated Non-small Cell Lung Cancer after failure of EGFR TKI Therapy

Clinical Study of Ivonescimab for First-line Treatment of Metastatic NSCLC Patients

This is a Phase 3 Randomized, double-blind, Multiregional Study of Ivonescimab Combined with Chemotherapy Versus Pembrolizumab Combined with Chemotherapy for the First-line Treatment of Metastatic Non-small Cell Lung Cancer. The primary endpoint is overall survival and progression free survival assessed by investigator. The key secondary endpoints include response and safety.

Symbiotic-Lung-10: A Study to Learn About PF-08634404 Alone or in Combination in Early-stage or Locally Advanced NSCLC

This study is being done to learn more about a new medicine called PF-08634404. The study team wants to understand how well it works when given alone or with chemotherapy. The study is for adults with early stage or locally advanced non-small cell lung cancer (NSCLC) that may or may not be removable with surgery. The study is seeking participants who: * Are aged 18 years or older * Have either: * Early-stage or locally advanced (Stage II or IIIA/B) NSCLC and are a candidate for neoadjuvant therapy, followed by surgical removal of the tumor. Neoadjuvant therapy is a treatment given as a first step to shrink the tumor before surgery. * Early-stage or locally advanced (Stage II or IIIA/B) NSCLC and are a candidate for adjuvant therapy and did not achieve a pathological complete response (pCR) from approved treatment that was administered before surgery. Adjuvant therapy is an additional cancer treatment given after the primary treatment to lower the risk that the cancer will come back. pCR is defined as absence of viable tumor in all surgically removed samples. * Locally advanced (Stage III) NSCLC that may not be removable with surgery, was treated with concurrent chemoradiotherapy (cCRT), and is a candidate for additional treatment, otherwise known as consolidation therapy. cCRT is chemotherapy and radiation given simultaneously. * Be in good physical condition and have healthy organs based on medical tests. * Do not have known actionable changes in DNA The study has 3 parts and each participant will be assigned to one part by their doctor based on their disease diagnosis: * Part A will test PF-08634404 given with chemotherapy in the neoadjuvant setting, followed by surgery. * Part B will test PF-08634404 alone in adults who already were treated with neoadjuvant chemo-immunotherapy, underwent surgery, and did not achieve pCR per tumor tissue pathology analysis. Neoadjuvant chemo-immunotherapy refers to the combination of chemotherapy with immunotherapy per local standard-of-care, given before surgical removal of the tumor. * Part C will test PF-08634404 alone in adults with unresectable disease who received cCRT and did not have progressive disease. Progressive disease refers to a condition that grows, spreads, or worsens. All treatments will be done at clinical study sites, where a trained medical team will monitor adults during and after each visit.

Symbiotic-Lung-20: A Study to Learn About the Study Medicine Called PF-08634404 in Combination With Different Anticancer Agents in Advanced Cancers

This study is being done to learn more about a new medicine called PF-08634404 and how it works when used with other cancer medicines in people who have advanced solid tumors. An advanced solid tumor is a type of cancer that has spread beyond its original location and cannot be removed by surgery or cured with standard treatments. To join in the study, participants must: * Be 18 years or older * Participants with advanced non-small cell lung cancer (NSCLC), a type of lung cancer that has spread to other parts of the body The study will look at: * Whether PF-08634404 is safe to use with other cancer medicines. * What side effects may happen. A side effect is anything the medicine does to your body that is not part of treating your disease. * Whether the combination of PF-08634404 and other cancer medicines can help treat solid tumors. The study has different parts, each testing PF-08634404 with a different cancer medicine: * Part A will test PF-08634404 with a medicine called sigvotatug vedotin. * Part B will test PF-08634404 with a medicine called PF-08046054/SGN-PDL1V Participants will receive the study medicines through an intravenous (IV) infusion (injected into the vein) at the study clinic. All treatments will take place at clinical trial sites, where trained medical staff will monitor participants during and after each visit.

Symbiotic-Lung-01 : A Study to Learn About the Study Medicine Called PF-08634404 in Combination With Chemotherapy in Adult Participants With Locally Advanced or Metastatic Non-Small Cell Lung Cancer

This study is being done to find out if a new medicine called PF-08634404, when given with chemotherapy, works better than the present standard treatment (pembrolizumab with chemotherapy) for adults with a type of lung cancer called non-small cell lung cancer (NSCLC) that is either locally advanced (spread to nearby tissues) or has spread to other parts of the body. To join the study, participants must meet the following conditions: * Be 18 years or older. * Have locally advanced (Stage IIIB/IIIC) or metastatic (Stage IV) squamous or non-squamous NSCLC. * Is not a candidate for complete surgical resection or curative chemoradiotherapy. * Do not have known actionable genomic alterations * Be treatment naïve for advanced or metastatic disease Participants in this study will be assigned to two different parts of the study depending on their type of tumor: participants with squamous NSCLC will be assigned to Part 1, while participants with non-squamous NSCLC will be assigned to Part 2. Each participant will be randomly assigned (like a flip of the coin) to one of two treatment groups in a blinded fashion: * Part 1 - Arm A or Part 2 - Arm C (Experimental Group): Will receive a new study medicine called PF-08634404 along with a kind of chemotherapy specific to the type of tumor. * Part 1 - Arm B or Part 2 - Arm D (Control Group): Will receive an approved medicine called pembrolizumab along with a kind of chemotherapy specific to the type of tumor. Participants will receive their assigned treatment through intravenous (IV) infusions, which means the medicine is given directly into a vein. The treatment will be given in cycles, participants will receive PF-08634404 or Pembrolizumab in combination with chemotherapy followed by maintenance with either PF-08634404 or Pembrolizumab monotherapy (Part 1) or PF-08634404 or Pembrolizumab in combination with a chemotherapeutic drug (Part 2). Participants will continue receiving treatment if it is helping and not experiencing serious side effects. The study will include regular visits for: * Treatment and health checks: while participant continues receiving treatment. * Tests to monitor how cancer responds: every 6 weeks during the first 48 weeks, then every 12 weeks thereafter.

Study of Izalontamab Brengitecan (BMS-986507) in Combination With Osimertinib Versus Osimertinib Monotherapy or Osimertinib in Combination With Platinum-based Chemotherapy for EGFRmt Non-small Cell Lung Cancer (IZABRIGHT-Lung02)

The purpose of this study is to evaluate izalontamab brengitecan (iza-bren) combined with osimertinib in participants with previously untreated, locally advanced or metastatic EGFR-mutant NSCLC, compared to osimertinib alone or osimertinib combined with platinum-based chemotherapy

Study of Pembrolizumab (MK-3475) Subcutaneous (SC) Versus Pembrolizumab Intravenous (IV) Administered With Platinum Doublet Chemotherapy in Participants With Metastatic Squamous or Nonsquamous Non-Small Cell Lung Cancer (NSCLC) (MK-3475-A86)

The purpose of this study is to evaluate pembrolizumab (MK-3475) subcutaneous (SC) administration as the first-line therapy in the treatment of metastatic squamous and nonsquamous NSCLC by assessing the pharmacokinetics (PK), safety, and efficacy of pembrolizumab SC injection in combination with standard-of-care chemotherapy. The primary hypothesis of the study is Pembrolizumab SC is noninferior to pembrolizumab intravenous (IV) for Cycle 1 Area Under Curve (AUC) and Cycle 6 minimal concentration (Ctrough) at steady state. Participants who discontinue study treatment after receiving the first course of 35 administrations of pembrolizumab (approximately up to 2 years) for reasons other than disease progression or intolerability, may be eligible for a second course of pembrolizumab for up to approximately 1 additional year if they have experienced radiographic disease progression per RECIST 1.1 as assessed by BICR after stopping first course treatment.

A Study Evaluating the Efficacy and Safety of Divarasib and Pembrolizumab Versus Pembrolizumab and Pemetrexed and Carboplatin or Cisplatin in Participants With Previously Untreated, KRAS G12C-Mutated, Advanced or Metastatic Non-Squamous Non-Small Cell Lung Cancer

The purpose of this study is to evaluate the efficacy and safety of divarasib and pembrolizumab compared with pembrolizumab and pemetrexed and carboplatin or cisplatin, for the first-line treatment of adult participants with KRAS G12C-mutated, advanced or metastatic non squamous non-small cell lung cancer (NSCLC).

A Study Evaluating the Safety, Activity, and Pharmacokinetics of Divarasib as a Single Agent or in Combination With Other Anti-Cancer Therapies in Participants With Previously Untreated Advanced or Metastatic Non-Small Cell Lung Cancer With a KRAS G12C Mutation

The purpose of this study is to evaluate the safety, pharmacokinetics (PK), and activity of single-agent divarasib or combined with other anti-cancer therapies in participants with previously untreated, advanced or metastatic non-small cell lung cancer (NSCLC).

A Study to Assess Adverse Events and Change in Disease Activity of Intravenous (IV) Telisotuzumab Adizutecan, Monotherapy or in Combination With Osimertinib, Compared to Standard of Care in Adult Participants With Locally Advanced or Metastatic EGFR-Mutated Non-Squamous Non-Small Cell Lung Cancer

Non-small cell lung cancer (NSCLC) is a common type of lung cancer where abnormal cells in the lungs grow out of control. The purpose of this study is to assess adverse events and change in disease activity of telisotuzumab adizutecan as a monotherapy or in combination with osimertinib compared to standard of care (SOC). Telisotuzumab adizutecan is an investigational drug being developed for the treatment of NSCLC. This study will be divided into two stages, in the first stage (phase 2) participants will receive 1 of 2 doses of telisotuzumab adizutecan as a monotherapy or in combination with osimertinib. In the second stage (phase 3) participants will receive the recommended phase 3 dose (RP3D) of telisotuzumab adizutecan, from the previous stage, or SOC. Approximately 490 adult participants with NSCLC will be enrolled in the study in 200 sites around the world. In phase 2, participants will receive 1 of 2 intravenous (IV) doses of telisotuzumab adizutecan as a monotherapy or in combination with oral osimertinib. In phase 3, participants will receive the IV RP3D of telisotuzumab adizutecan, or SOC. The study will run for a duration of approximately 69 months. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, questionnaires and side effects.

Beamion LUNG-1: A Study to Test Different Doses of Zongertinib in People With Different Types of Advanced Cancer (Solid Tumours With Changes in the HER2 Gene)

The study has 2 parts. The first part is open to adults with different types of advanced cancer (solid tumours with changes in the HER2 gene) for whom previous treatment was not successful. The second part is open to people with non-small cell lung cancer with a specific mutation in the HER2 gene. The purpose of the first study part is to find the highest dose of a medicine called zongertinib the participants can tolerate. Once this dose is found, it will be used in the second study part to test whether zongertinib can make tumours shrink. In this study, zongertinib is given to people for the first time. Participants take zongertinib as tablets once a day or twice a day. The participants are in the study for as long as they benefit from and can tolerate treatment. Study doctors regularly check the participants' health and monitor the tumours. The doctors also take note of any unwanted effects that could have been caused by zongertinib.