Input:
VG161 is a recombinant human-IL12/15/PDL1B oncolytic HSV-1 Injectable. This Phase I study
 will be conducted in HSV-seropositive subjects with advanced malignant solid tumors that are
 refractory to conventional therapies. This is an open label study to determine the safety and
 tolerability of VG161, and recommended dose of VG161 for Phase II trials.
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 Inclusion Criteria:
 1. Males or females aged within 18 to 80 years.
 2. Subject with late stage carcinoma which is refractory/relapsed after and/or intolerant
 of standard therapies or for which no standard therapy exists.
 3. There is at lease one injectable tumor lesion that meet the requirements of the
 assigned dose level. The superficial lesions are preferred, and the deep lesions that
 can be injected under the guidance of B ultrasound or computed tomography (CT) scan
 can also be selected.
 4. Eastern Cooperative Oncology Group (ECOG) scores 0 or 1.
 5. Life expectancy is at least 3 months.
 6. Required organ function:
 1) Hematology blood (no blood transfusion or colony stimulating factor treatment within 14
 days): Absolute neutrophil count (ANC)≥1.5×10^9L, Platelets ( PLT)≥75×10^9L, hemoglobin
 (Hb)≥85g/L; 2) Liver function: Total Serum bilirubin (TBIL)≤1.5×ULN (the upper limit of the
 reference range), Alanine aminotransferase (ALT)≤3×ULN, aspartate aminotransferase
 (AST)≤3×ULN (acceptable for patients with liver metastasis or liver cancer: TBIL≤5×ULN,
 AST≤5×ULN, ALT≤5×ULN); 3) Renal function: Serum creatinine≤1.5×ULN, and creatinine
 clearance≥50 ml/min (calculated per Cockcroft-Gault formula); 4) Coagulation function:
 activated partial thromboplastin time (APTT)≤1.5×ULN, international standardized ratio
 (INR)≤1.5×ULN.
 7. Subjects of childbearing potential (male and female) must agree to use a reliable
 contraceptive method (hormone or barrier method or abstinence) during the study and for at
 least 90 days following the last dose; females of childbearing potential must have a
 negative blood or urine pregnancy test within 7 days of study enrollment.
 8. Signed written informed consent.
 Exclusion Criteria:
 1. Subject in prior anti-tumor therapies such as chemotherapy, radiotherapy, biotherapy,
 endocrinotherapy, targeted therapy, immunotherapy within 4 weeks of study treatment
 initiation.
 2. Participation in clinical trials of any other investigational agents within 4 weeks of
 study treatment initiation.
 3. Major organ surgery (excluding puncture biopsy) or significant trauma within 4 weeks
 of study treatment initiation.
 4. Patients who received systemic treatment with either corticosteroids ( >10 mg/ daily
 prednisone or equivalent) or other immunosuppressive medications within 14 days of
 study treatment initiation.
 5. Subjects with any ≥Grade 1 toxicity (as per NCI CTC AE Version 5.0) related to prior
 anti-cancer therapy (except for toxicity that the investigator assessed to be no
 safety risk, such as alopecia.).
 6. Subjects with any uncontrolled active Central Nervous System (CNS) metastasis or
 meningeal metastasis with clinical symptoms.
 7. Seronegative for Herpes Simplex Virus (HSV) (HSV-1IgG and HSV-1IgM).
 8. Subjects with the relapse of HSV infection and relevant clinical manifestations, such
 as lip herpes, herpes keratitis, herpes dermatitis, and genital herpes.
 9. Subjects with other uncontrolled active infections.
 10. Known history of immunodeficiency and test positive of human immunodeficiency virus
 (HIV).
 11. Active infection of hepatitis B (HBV) (hepatitis b virus titer higher than the
 detection limit or those requiring antiviral therapy), or hepatitis C virus (HCV).
 12. History of severe cardiovascular disease:
 1)Ventricular arrhythmias requiring clinical intervention; 2)QTc interval >480 ms; 3)Acute
 coronary syndrome, congestive heart failure, stroke or other cardiovascular events of III
 grade or above within 6 months; 4)The cardiac function grade≥II or left ventricular
 ejection fraction (LVEF) <50% per the New York Heart Association (NYA); 5)Uncontrolled
 hypertension. 13. Subjects with active or past autoimmune diseases that are likely to recur
 (e.g. systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.); acceptable for
 patients with clinically stable autoimmune thyroiditis.
 14. Subjects with any prior ≥Grade 3 immune-related adverse event (irAE) while receiving
 any previous immunotherapy agent.
 15. known to have alcohol or drug dependence. 16. Persons with mental disorders or poor
 compliance. 17. Pregnant or lactating women. 18. Subjects with any significant unrelated
 systemic illness that to the investigator's opinion would compromise the subject's
 eligibility to participate the study.


Input:
This is a phase 1a/1b, multicentre, open-label, non-randomized study of NG-641 in combination
 with nivolumab in patients with metastatic or advanced epithelial tumours.
 To characterize the safety and tolerability of NG-641 in combination with nivolumab in
 patients with metastatic or advanced epithelial tumours and to determine the recommended dose
 of NG-641 in combination with nivolumab for further development in patients with metastatic
 or advanced epithelial tumours
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 Inclusion Criteria:
 - Provide written informed consent to participate
 - Patients must have one of eleven histologically or cytologically confirmed
 metastatic/advanced carcinoma or adenocarcinoma that has progressed after at least one
 line of systemic therapy and are incurable by local therapy (contact Sponsor for more
 details regarding the tumour types)
 a. Tumour types included are: urothelial carcinoma, squamous cell carcinoma of the
 head and neck (SCCHN), microsatellite instability (MSI)-high/deficient mismatch repair
 (dMMR) cancer, non-small cell lung cancer (NSCLC), uterine/endometrial cancer,
 cervical cancer, oesophageal cancer, gastric cancer, triple-negative breast cancer
 (TNBC), cutaneous squamous cell carcinoma and hepatocellular carcinoma
 - At least one measurable site of disease according to RECIST Version 1.1 criteria; this
 lesion must be either (i) outside a previously irradiated area or (ii) progressive if
 it is in a previously irradiated area
 - Prior treatment with a PD-1/PD-L1 inhibitor (prior PD-1/PD-L1 may have been given as
 monotherapy or combination therapy)
 - Tumour accessible for biopsy
 - Aged 18 years or over
 - ECOG performance status 0 or 1
 - Predicted life expectancy of ≥6 months
 - Adequate lung reserve (Oxygen saturation on ambient air at sea level ≥95% or the
 equivalent based on altitude (i.e. ≥90% at 5000 feet))
 - Adequate renal function:
 1. Creatinine ≤1.5 × upper limit of normal (ULN) and estimated glomerular filtration
 rate (eGFR) ≥60 mL/minute/1.73m2 (or measured creatinine clearance ≥60 mL/minute)
 2. Spot albumin-to-creatinine ratio (ACR) for proteinuria at screening and baseline
 ≤30 mg/g. Patients with a spot ACR >30 mg/g who undergo a subsequent 24-hour
 urinary protein test with a result of <1 g/24 h may be included
 - Adequate hepatic function:
 1. Serum total bilirubin ≤1.5 × ULN OR direct bilirubin ≤1 × ULN
 2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 × ULN
 range
 3. Albumin ≥3 g/dL
 - Adequate bone marrow function:
 1. Absolute neutrophil count ≥1.5 × 109/L
 2. Platelets ≥100 × 109/L
 3. Haemoglobin ≥90 g/L (9 g/dL)
 - Coagulation profile within the normal range
 - Meeting reproductive status requirements:
 1. Must not be pregnant or breastfeeding
 2. Female patients of childbearing potential, must have a negative serum or urine
 pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human
 chorionic gonadotrophin) within 24 hours before the first dose of study treatment
 3. Female patients of childbearing potential who are heterosexually active must
 agree to use a highly effective method of contraception to prevent pregnancy, for
 the duration of study treatment and 6 months following the last dose of study
 treatment. Female patients who are continuously not heterosexually active are
 exempt from contraceptive requirements, but must still undergo pregnancy testing
 4. Female patients who are heterosexually active, irrespective of childbearing
 status, must ensure their male partner agrees to use a condom with spermicide
 during sexual intercourse for the duration of study treatment and 6 months
 following the last dose of study treatment
 5. Patients must be willing to refrain from egg donation during treatment and for at
 least 6 months following the last dose of study treatment
 6. Male patients who are sexually active with men or women must agree to use a
 condom with spermicide during intercourse for the duration of study treatment and
 6 months following the last dose of study treatment. In addition, patients must
 be willing to refrain from sperm donation during this time.
 - Exclusion Criteria:
 - Prior or planned allogeneic or autologous bone marrow or organ transplantation
 - Splenectomy
 - Active infections requiring antibiotics, physician monitoring or systemic therapy
 within 1 week of the anticipated first dose of study drug, or recurrent fevers
 (>38.0˚C) associated with a clinical diagnosis of active infection
 - Treatment with the antiviral agents: ribavirin, adefovir, lamivudine or cidofovir
 within 10 days prior to the first dose of study treatment; or pegylated interferon in
 the 4 weeks before the first dose of study treatment
 - Active viral disease or positive test for hepatitis B virus using hepatitis B surface
 antigen test or positive test for HCV using HCV ribonucleic acid (RNA) or HCV antibody
 test indicating acute or chronic infection. Positive test for HIV or AIDS
 - Patients who have active, known or suspected autoimmune disease that has required
 systemic therapy in the past 2 years, are immunocompromised in the opinion of the
 Investigator, or are receiving systemic immunosuppressive treatment
 a. Patients with vitiligo, type I diabetes mellitus, asthma/atopy, residual
 hypothyroidism due to autoimmune disease (which only requires hormone replacement
 therapy), or conditions not expected to recur in the absence of an external trigger
 are permitted to enrol providing they comply with the other eligibility criteria
 relating to renal function. Use of inhaled corticosteroids, local steroid injection,
 or steroid eye drops is allowed
 - Treatment with any live, live-attenuated or COVID-19 vaccine in the 30 days before the
 first dose of NG-641 or nivolumab (COVID-19 vaccines known not to be
 live/live-attenuated or based on an adenoviral vector (e.g. mRNA vaccines) are not
 subject to the 30-day exclusion)
 - Treatment with any other vaccine (including known non-live/live-attenuated and
 non-adenoviral COVID-19 vaccines) in the 7 days before the first dose of NG-641
 - History of prior Grade 3-4 acute kidney injury or other clinically significant renal
 impairment
 - History of clinically significant interstitial lung disease or non-infectious
 pneumonitis
 - Lymphangitic carcinomatosis (clinically suspected or radiographic evidence)
 - Infectious or inflammatory bowel disease in the 3 months before the first dose of
 study treatment
 - Myocardial infarction, stroke or other significant cardiovascular or cerebrovascular
 event in the 12 months before the first dose of study treatment
 - Pulmonary embolism, deep vein thrombosis, or other uncontrolled thromboembolic event
 in the 12 months before the first dose of study treatment, or current treatment with
 therapeutic or prophylactic anticoagulation therapy
 - Grade 3 or 4 gastrointestinal bleeding (or risk factors for gastrointestinal bleeding)
 or haemoptysis in the 3 months before first dose of study treatment, or any history of
 bleeding requiring an investigative procedure (e.g. endoscopy), transfusion or
 hospitalisation in the 12 months before the first dose of study treatment
 - Tumour location/extent considered by the Investigator to present a significant risk if
 tumour flare or necrosis were to occur (e.g. an initial increase in tumour size that
 may lead to intestinal, airway or ureter obstruction, or penetrating tumour
 infiltration of major blood vessels, or other hollow organs potentially at risk of
 perforation)
 - Use of the following prior therapies/treatments:
 1. Treatment with any other enadenotucirev-based virus (parent virus or
 transgene-modified variants), or fibroblast activation protein (FAP) targeting
 agent at any time
 2. Treatment with an investigational or licensed anti-cancer monoclonal antibody
 (mAb), immune checkpoint inhibitor, immune stimulatory treatment or other
 biological therapy in the 28 days prior to the first dose of study treatment.
 - Prior anti-PD-1/PD-L1 therapy is permitted without a 'washout' phase c. Treatment with
 an investigational or licensed chemotherapy, targeted small molecule or other
 investigational drug in the 14 days or five half-lives (whichever is shorter) before
 the first dose of study treatment d. Major surgery in the 28 days before the first
 dose of study treatment e. Radiation therapy in the 14 days before the first dose of
 study treatment f. Treatment with complementary medications (e.g. herbal supplements
 or traditional Chinese medicines) to treat the disease under study within the 14 days
 prior to first study treatment. Such medications are permitted if they are used as
 supportive care g. Bisphosphonate therapy or treatment with Receptor Activator of
 Nuclear factor Kappa-Β (RANK)-ligand inhibitors for metastatic bone disease is
 permitted
 - All toxicities attributed to prior anti-cancer therapy (including radiation therapy)
 other than alopecia must have resolved to Grade 1 or baseline before the first dose of
 study treatment
 - Known allergy or hypersensitivity (Grade ≥3) to NG-641 transgene, immune checkpoint
 inhibitor products or formulation, or other monoclonal antibodies
 - Discontinuation from prior treatment with an immune therapy due to a Grade ≥3
 immune-related AE, or any history of life-threatening toxicity related to prior immune
 therapy
 - Other prior malignancy active within the previous 3 years, except for local or organ
 confined early stage cancer that has been definitively treated with curative intent,
 does not require ongoing treatment, has no evidence of residual disease and has a
 negligible risk of recurrence and is therefore unlikely to interfere with the primary
 and secondary endpoints of the study, including response rate and safety
 - Symptomatic brain metastases or any leptomeningeal metastases that are symptomatic
 and/or requires treatment
 - Any serious or uncontrolled medical disorder that, in the opinion of the Investigator
 or the Medical Monitor, may increase the risk associated with study participation or
 study treatment administration, impair the ability of the patient to receive protocol
 therapy or interfere with the interpretation of study results


Input:
This is a global, multicenter, open-label pre-approval access program to provide access to
 pralsetinib (BLU-667) until such time that pralsetinib becomes available through other
 mechanisms or the Sponsor chooses to discontinue the program.
 ;NA;
 Inclusion Criteria:
 1a. Pathologically documented and definitively diagnosed non-resectable or metastatic NSCLC
 with a RET fusion for patients who are either treatment naïve, or who have been previously
 treated with systemic therapy. In the presence of a primary driver mutation, such as EGFR,
 ALK, ROS1, NTRK, or BRAF, the patient must be treated with the appropriate targeted therapy
 first. Patient is eligible if RET fusion is confirmed AND patient has undergone initial
 therapy for his/her driver mutation, or
 1b. Pathologically documented and definitively diagnosed RET mutation in advanced MTC
 patients who are treatment naïve or who have been previously treated with MKI therapy, or
 1c. Pathologically documented and definitively diagnosed advanced solid tumor with an
 oncogenic RET fusion previously treated with standard of care appropriate for the tumor
 type.
 2. If previously treated with a selective RET inhibitor (e.g., RETEVMO), confirm patient
 has not progressed but has discontinued due to adverse event(s).
 3. Patient is not eligible for an ongoing study of pralsetinib or cannot access an ongoing
 study of pralsetinib.
 4. Patient is ≥ 12 years of age. 5. Patient has adequate vital organ function, including
 heart, lungs, liver, kidneys, bone marrow and endocrine, and is expected to tolerate
 therapy with a tyrosine kinase inhibitor.
 6. No presence of clinically symptomatic interstitial lung disease or interstitial
 pneumonitis, including radiation pneumonitis (i.e., affecting activities of daily living or
 requiring therapeutic intervention).
 7. Patient or patient's legal guardian, if permitted by local regulatory authorities,
 intends to provide informed consent prior to the start of treatment with pralsetinib.
 8. Patient does not require therapy with a concomitant medication that is a strong
 inhibitor or strong inducer of cytochrome P450 (CYP) 3A4.
 9. Patient has not received treatment with any systemic anticancer therapy (except for
 immunotherapy or other antibody therapies) and all forms of radiotherapy within 14 days or
 5 half-lives prior to the first dose of pralsetinib. Pralsetinib may be started within
 these washout periods if considered by the healthcare provider to be safe and within the
 best interest of the patient, with prior Sponsor approval.
 10. Patient has not received treatment with any immunotherapy or other antibody therapy
 within 28 days prior to the first dose of pralsetinib (immune related toxicities must have
 resolved to < Grade 2 prior to starting pralsetinib).
 11. Patient has not had a major surgical procedure (minor surgical procedures such as
 central venous catheter placement, tumor needle biopsy, and feeding tube placement are not
 considered major surgical procedures) within 14 days prior to the first dose of
 pralsetinib.
 12. Women must be willing, if not postmenopausal or surgically sterile, to abstain from
 sexual intercourse or employ highly effective contraception during pralsetinib
 administration period and for at least 30 days after the last dose of pralsetinib. Men, if
 not surgically sterile, must be willing to abstain from sexual intercourse or employ highly
 effective contraception during pralsetinib administration period and for at least 90 days
 after the last dose of pralsetinib.
 13. Women must not be pregnant or breastfeeding.


Input:
This clinical trial is a Phase 1-2, open-label, sequential-group, dose-escalation and
 cohort-expansion study evaluating the safety, pharmacokinetics (PK), pharmacodynamics, and
 antitumor activity of Zotatifin (eFT226) in subjects with selected advanced solid tumor
 malignancies.
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 Key Criteria:
 Parts 1a and 1b (Dose Escalation + Fulvestrant):
 - Patient has histological or cytological confirmation of breast cancer.
 - Patient has metastatic disease or locoregionally recurrent disease which is refractory
 or intolerant to existing therapy(ies) known to provide clinical benefit.
 - Patient has had prior chemotherapy, endocrine therapy, or other therapy as follows:
 - Minimum of one prior line of therapy for advanced/metastatic disease.
 - Maximum of five prior lines of therapy for advanced/metastatic disease.
 - Recurrence or progression on at least one line of endocrine therapy in the
 advanced/metastatic disease setting.
 - Prior treatment has included a CDK4/6 inhibitor.
 - Tumor is ER+ (defined as ER IHC staining > 0%).
 Cohort EMNK:
 - Patient has undergone treatment with platinum-based chemotherapy and an anti-PD-1/L1
 agent, if appropriate.
 - Tumor has a known KRAS-activating mutation; Patients with KRAS G12C mutations are
 excluded.
 Cohort EMBF:
 - Patient has had prior chemotherapy, endocrine therapy, or other therapy as follows:
 - Minimum of one prior line of therapy for advanced/metastatic disease.
 - Maximum of five prior lines of therapy for advanced/metastatic disease.
 - Recurrence or progression on at least one line of endocrine therapy in the
 advanced/metastatic disease setting, which may include combination therapy (eg,
 with a CDK4/6 inhibitor).
 - Tumor is ER+ (defined as ER IHC staining > 0%) and has FGFR amplification.
 Cohort EMBH:
 - Patient has had prior chemotherapy, endocrine therapy, or other therapy as follows:
 - Minimum of one prior line of therapy for advanced/metastatic disease.
 - Minimum of one line of HER2-directed therapy Note: Prior treatment with CDK4/6
 inhibitors is permitted.
 - Tumor is ER+ (defined as ER IHC staining > 0%) and HER2+ (defined as HER2 3+ IHC
 staining or HER2 2+ and FISH+).
 Cohort ECNS:
 - Patient has histologically or cytologically confirmed stage IIIB (pleural or
 pericardial effusion) or stage IV NSCLC.
 - Patient has undergone treatment with platinum-based chemotherapy and an anti-PD-1/L1
 agent, if appropriate. Note: Patients who have declined approved therapy(ies) or who
 per treating physician are not eligible for approved therapy(ies) (eg, due to
 intolerance) may be eligible following discussion with the Medical Monitor.
 - Tumor has a known G12C KRAS-activating mutation. Note: Patients who have been
 previously treated with KRAS-specific therapy are excluded.
 Cohort ECBF:
 - Patient has had prior chemotherapy, endocrine therapy, or other therapy as follows:
 - Minimum of one prior line of therapy for advanced/metastatic disease.
 - Maximum of five prior lines of therapy for advanced/metastatic disease.
 - Recurrence or progression on at least one line of endocrine therapy in the
 advanced/metastatic disease setting.
 - Prior treatment has included a CDK4/6 inhibitor.
 - Tumor is ER+ (defined as ER IHC staining > 0%).
 Cohort ECBF+A:
 - Patient has had prior chemotherapy, endocrine therapy, or other therapy as follows:
 - Minimum of one prior line of therapy for advanced/metastatic disease.
 - Maximum of five prior lines of therapy for advanced/metastatic disease.
 - Recurrence or progression on at least one line of endocrine therapy in the
 advanced/metastatic disease setting.
 - Tumor is ER+ (defined as ER IHC staining > 0%) and HER2- (defined as absence of HER2
 3+ IHC staining and/or absence of FISH+).
 Cohort ECBT:
 - Patient has progressed after treatment with at least one approved anti-HER2 agent and
 has been administered at least one line of chemotherapy.
 - Tumor is HER2+ (defined as HER2 3+ IHC staining or HER2 2+ and FISH+). Cohorts EMBF,
 EMBH, ECBF, ECBF+A: There is no limit on the number of lines of prior endocrine
 therapies.
 Cohort ECBF-D1:
 - Patient has metastatic disease or locoregionally recurrent disease which is refractory
 or intolerant to existing therapy(ies) known to provide clinical benefit.
 - Patient has had prior chemotherapy, endocrine therapy, or other therapy as follows:
 - Minimum of one prior line of therapy for advanced/metastatic disease.
 - Maximum of five prior lines of therapy for advanced/metastatic disease.
 - Recurrence or progression on at least one line of endocrine therapy in the
 advanced/metastatic disease setting.
 - Prior treatment has included a CDK4/6 inhibitor.
 - Tumor is ER+ (defined as ER IHC staining > 0%).
 - Tumor has amplification of Cyclin D1 as determined by next generation sequencing or in
 situ hybridization.