A study of GSK5864399 administered alone or in combination with other anti-cancer agents in participants with solid tumours

Participants are eligible to be included in the study only if all of the following criteria apply:

• Is at least 18 years of age or the legal age of consent.
• Has histologically confirmed unresectable metastatic disease of either:

non-small cell lung cancer that has progressed through at least 1 prior line of systemic therapy

• Has at least 1 target lesion per RECIST 1.1, as determined by the investigator.
• Participants must provide Formalin-Fixed, Paraffin-Embedded (FFPE) tumour tissue sample taken from primary cancer or metastatic site.
• Is willing to use adequate contraception.
• Is capable of giving signed informed consent.
• Has an ECOG performance status of 0 or 1.
• Has adequate organ function.

Participants are excluded from the study if any of the following criteria

• Has a malignancy (except disease under study) that has progressed or required active treatment within the past 24 months (with some exceptions).
• Has had any major surgery within 28 days prior to first dose.
• Has any history of prior allogeneic or autologous bone marrow transplant or other solid organ transplant.
• Has known sensitivity to study intervention components or excipients or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.
• Has known active infectious disease or a serious infection within 4 weeks prior to the first dose.
• Has a history (in prior year) of clinically significant or uncontrolled cardiovascular disease.
• Has untreated brain or Central Nervous System (CNS) metastases or brain/CNS metastases that have progressed.
• Any evidence of small cell or sarcomatoid histology for the NSCLC participants.
• Has a history of autoimmune disease that has required systemic treatments in the 2 years prior to screening.
• Has any active renal condition.
• Has a history of discontinuing prior treatment due to TEAE of ILD/pneumonitis
• Has a history of (non-infectious) Interstitial Lung Disease (ILD)/pneumonitis that required active treatment within 4 weeks before study-intervention administration.
• Has ongoing adverse reaction(s) from prior therapy that has(have) not recovered to Grade 1 or to the baseline status preceding prior therapy (with some exclusions).
• Has any serious and/or unstable medical or psychiatric disorder or other condition(s) (including laboratory assessment abnormalities) that could interfere with the participant’s safety, obtainment of informed consent, or compliance to the study procedures.
• Has symptomatic and/or progressive pleural metastases or cytologically confirmed malignant pleural effusions despite appropriate analgesia and thoracenteses respectively. Participants with previously treated pleural metastases/malignant pleural effusions with clinical stability demonstrated for at least 4 weeks prior to first dose are not excluded from participation.
• Has received immunosuppressive agents within 30 days prior to first dose of study intervention (or requires long term [30 days or longer]).
• Has received any prior therapy targeting CEACAM5.
• Has received any live vaccine within 30 days of first dose. Vaccination against COVID-19 using vaccines that are authorized via the appropriate regulatory mechanisms (e.g., Emergency Use Authorization, Conditional Marketing Authorization, or Marketing Authorization Application) are not exclusionary. Messenger Ribonucleic acid (mRNA) and adenoviral-based COVID-19 vaccines are considered non-live. If a COVID-19 vaccine is administered at any time, the date of COVID-19 vaccination must be entered in the electronic Case Report Form (eCRF).
• Has received any transfusion of blood products (including platelets or red blood cells) or administration of colony-stimulating factors (including Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF), granulocyte macrophage colony-stimulating factor, or recombinant erythropoietin) within 14 days before first dose.
• History of local radiotherapy within 2 weeks prior to the first dose of study intervention; more than 30% of bone marrow irradiation or extensive radiotherapy within 4 weeks before the first dose of study intervention.
• Is currently enrolled or has participated in any other clinical study involving an investigational study intervention or any other type of interventional medical research and/or has received treatment with any anticancer or investigational agent within 4 weeks prior to first dose. Participation in study follow-up part without IMP administration, non-interventional registry or epidemiological study is allowed.
• Has a known Human Immunodeficiency Virus (HIV) infection AND meets at least one of the following criteria:

Has received treatment with an HIV 1 immunotherapeutic vaccine within 90 days of screening. Participants with history of CDC Stage 3 disease (also known as AIDS defining disease are eligible provided all other applicable criteria are met) if the AIDS-defining disease has been treated and cured or is stable for at least 3 months prior to screening. Cutaneous Karposi’s Sarcoma not requiring systemic therapy is not exclusionary.

• Is unable to adhere to the protocol-defined schedule of assessments, including requirements for the follow-up period of the study.
• Has an Alanine Aminotransferase (ALT) or AST value >2.5x Upper Limit of Normal (ULN) and/or for participants with documented liver metastases/tumour infiltration has an ALT or AST value >5x ULN.
• Has a total bilirubin value >1.5x ULN. Participants with Gilbert’s syndrome can be included with a total bilirubin value >1.5x ULN, provided direct bilirubin is ≤1.5x ULN and participant otherwise meets entry criteria.
• Has cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal/gastric varices, or persistent jaundice. Stable noncirrhotic chronic liver disease (including Gilbert’s syndrome or asymptomatic gallstones) or hepatobiliary involvement of malignancy is acceptable if the participant otherwise meets entry criteria.
• Has documented presence of Hepatitis B surface antigen (HBsAg) or Hepatitis B core antibody (HBcAb) at screening or within 3 months prior to the first dose of study intervention. In Japan, the following modification is applied; Has documented presence of HBsAg, HBcAb, or Hepatitis B surface antibody (HBsAb) (except for presence of HBsAb attributable to previous vaccination) at screening or within 3 months prior to the first dose of study intervention. For participants with presence of HBsAb, Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) will be tested every 3 months.
• Has a positive Hepatitis C Virus (HCV) antibody test result at screening or within 3 months prior to the first dose of study intervention unless HCV RNA is negative, indicating past resolved HCV infection, including participants who have undergone curative treatment. Participants with a positive HCV antibody test result due to prior resolved disease, including those who have undergone curative HCV treatment, can be enrolled if a confirmatory negative HCV RNA test is obtained and the participant otherwise meets entry criteria.
• Has a positive HCV RNA test result at screening or within 3 months prior to the first dose of study intervention. The HCV RNA test is optional, and participants with a negative HCV antibody test are not required to undergo HCV RNA testing as well.
• Has baseline QT interval corrected for heart rate (QTc)>480 msec.