Dose Escalation Group: CPI-300 will be administered via intravenous infusion once every 2 weeks for up to 6 dose levels using an accelerated titration method followed by a conventional 3 + 3 study design

CPI-300 will be administered via intravenous infusion on Day 1 of a 14-Day cycle

CPI-300

This is a prospective, open-label, single arm, non-randomized study of CPI-300 in patients with advanced tumors. CPI-300 is administered via intravenous infusion using an accelerated titration method followed by a conventional 3 + 3 study design to identify the maximum tolerated dose (MTD).

Up to 6 dose levels of CPI-300 will be tested. MTD will be defined as the dose associated with a dose limiting toxicity (DLT) in less than or equal to 33% of patients at the dose level tested. Dose limiting toxicity (DLT) is defined as one of the following events occurring from the intravenous injection of CPI-300 within 28 days:

* Grade 4 or greater treatment related adverse events
* Any Grade 3 or greater treatment related non-hematologic, non-dermatologic toxicity (including nausea, vomiting or diarrhea lasting more than 72 hours)

Blood samples will be drawn to determine drug blood concentrations for pharmacokinetic assessment.

accelerated titration method followed by a conventional 3 + 3 dose escalation study design

Phase I Study of CPI-300 in Patients With Advanced Tumors

A Phase 1, First-in-Human Study Evaluating the Safety, Tolerability, and Pharmacokinetics of CPI-300 Via Intravenous Infusion in Patients With Advanced Solid Tumors

To determine the maximum tolerated dose (MTD), which is defined as the highest dose level at which number of patients reporting a dose limiting toxicity (DLT) is less than or equal to 33%

To assess clinical benefit by response rate and resolution of symptoms, which will be reported as response rate (%)

To assess adverse effect as either treatment-related or non-treatment-related as defined by CTCAE

To evaluate maximum plasma concentration (Cmax) of CPI-300 in patients tested

To evaluate area under the curve (AUC) of CPI-300 in patients tested

Coordination Pharmaceuticals, Inc.

* Dosage form: injection
* Specification: 240 mg / 8 ml/Vial

Dose-limiting toxicity (DLT) are assessed during the first 3 weeks (21 days) after initial administration. Then, the intended dosing frequency is every 2 weeks (Q2W).

Intravenous Infusion

Jian Zhang, Professor

This study is a single arm, non-randomized, open label, multiple doses phase I/II international, multicenter clinical trial to evaluate safety, tolerability, PK/PD, immunogenicity and preliminary efficacy in subjects with advanced malignant neoplasm. The study is consisted of two stages: dose escalation and clinical expansion.

Only Phase I has been submitted to US FDA,and the protocol number is still the same as 6MW3211-2021-CP101.The US title is : A Phase 1, First-in-Human (FIH), Multicenter, Open-Label, Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of 6MW3211 in Patients with Advanced Malignancies .

Six cohorts are included in dose escalation stage, at doses of 0.3\~45 mg/kg, respectively. Safety, tolerability, and dose-limiting toxicity (DLT) are assessed during the first 3 weeks (21 days) after initial administration. Then, the intended dosing frequency is every 2 weeks (Q2W), IV.

From the first study drug administration, some dosing cycles will be observed for phase I, initial tumor efficacy assessments will be performed at week 7, after that tumor efficacy assessment will be carry out for every 6 weeks.

A Clinical Study of 6MW3211 Injection in the Treatment of Advanced Malignant Neoplasm

Phase I/II Clinical Trial of 6MW3211 Injection to Evaluate Safety, Tolerability, PK/PD, Immunogenicity and Preliminary Efficacy in Subjects With Advanced Malignant Neoplasm.(Only Phase I Has Been Submitted to US FDA)

Time at which maximum concentration(Tmax)

Mabwell (Shanghai) Bioscience Co., Ltd.

Subjects will receive 6MW3511 by intravenous administration.

This is a phase I/II , open-label, multicenter single arm study designed to evaluate the safety, tolerability, pharmacokinetic (PK), and immunogenicity of 6MW3511.

This is a Phase I/II, open-label, dose-escalation trial with consecutive parallel-group expansion in selected solid tumor indications. The study consists of a dose escalation phase to determine the maximum tolerated dose (MTD), or recommended Phase 2 dose (RP2D) for 6MW3511, and a dose expansion phase which will characterize treatment of 6MW3511 at the RP2D.

6MW3511 in Patients With Advanced Solid Tumor

A Phase I/II, Multicenter, Open-Label, Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Pharmacodynamics of 6MW3511 in Patients With Advanced Solid Tumor

DLTs will be assessed during the first 3 weeks of treatment for dose-escalation phase.

Characterization of incidence, severity and abnormal clinically significant laboratory findings of AEs.

The ORR is defined as the proportion of subjects with confirmed CR or confirmed PR, based on RECIST Version 1.1.

The DCR is defined as the proportion of subjects with CR, PR, or SD (subjects achieving SD will be included in the DCR if they maintain SD for ≥8 weeks) based on RECIST Version 1.1.

The endpoints for assessment of PK of 6MW3511 include serum concentrations of 6MW3511 at different timepoints after administration.

The immunogenicity of 6MW3511 will be assessed by summarizing the number of subjects who develop detectable anti-drug antibodies (ADAs).

Symptoms and General Pathology

All Conditions

Blood and Lymph Conditions

Neoplasms

Heart and Blood Diseases

Rare Diseases

Fibrosis

Myeloproliferative Disorders

Polycythemia Vera

Polycythemia

Primary Myelofibrosis

Thrombocytosis

Thrombocythemia, Essential

Splenomegaly

Bone Marrow Diseases

Hematologic Diseases

Bone Marrow Neoplasms

Hematologic Neoplasms

Blood Platelet Disorders

Hemostatic Disorders

Blood Coagulation Disorders

Hemorrhagic Disorders

Chronic Myeloproliferative Disorders

Essential Thrombocythemia

intravenous in dose cohorts of 70mg/m2 or 180 mg/m2

AVID200

John Mascarenhas, MD

Ruben Mesa, MD

Ronald Hoffman, MD

Increased levels of TGF-β1 were detected in serum, plasma and BM and positively correlated with both grade of BMF and extent of leukemic cell infiltration in the marrow. TGF-β likely plays a dual role in promoting myelofibrosis and myeloproliferation, both of which are the bone marrow morphologic hallmark of MF. AVID200 is a drug that targets TGF-β1 and TGF-β3. The study team hypothesizes that inhibiting the TGF-β signaling pathway in MF will decrease the fibrogenic stimuli leading to myelofibrosis and concomitantly interrupt myeloproliferation and restore normal hematopoiesis.

This is a first in human, open-label, multicenter, Phase I/Ib trial of AVID200. Patients must have intermediate-2 or higher primary myelofibrosis (PMF), post-essential thrombocythemia or polycythemia-vera related MF (Post ET/PV MF). This study will enroll up to 24 patients. AVID200 is delivered by IV infusion on day 1 of each 3 week cycle.

This is a first in human, open-label, multicenter, Phase I/Ib trial of AVID200. To date, there is no therapy for MF evaluated in the clinic that clearly demonstrates the ability to target the malignant HSC and result in effective and reproducible bone marrow morphologic, cytogenetic and molecular responses. Medicinal therapies that result in disease course modification are urgently needed in this chronic and progressive myeloid malignancy. TGF-β likely plays a dual role in promoting myelofibrosis and myeloproliferation, both of which are the bone marrow morphologic hallmark of MF. The study team proposes that inhibiting the TGF-β signaling pathway in MF will decrease the fibrogenic stimuli leading to myelofibrosis and concomitantly interrupt myeloproliferation and restore normal hematopoiesis. AVID200 is a fusion protein containing TGF-β receptor ectodomains fused to a human Fc IgG domain. AVID200 is a potent TGFβ trap with antibody-like properties which has pM potency against two of the three TGFβ ligands, TGFβ1 and β3.

MPN-RC 118 AVID200 in Myelofibrosis

Phase I Study of AVID200 in Patients With Myelofibrosis (Myeloproliferative Neoplasms Research Consortium [MPN-RC] 118)

Cohorts of 3 patients with a maximum evaluable sample size of 12 patients and a target toxicity rate of 30% to estimate the MTD. Each cycle is 21 days.

Subjects attaining at least a CI (clinical improvement) by IWG/ELN criteria, or a decrease in bone marrow fibrosis by ≥1 grade with otherwise stable disease, will be allowed to continue AVID200 in the extension phase of the trial.

response by IWG/ELN criteria at the end of Cycle 6 and Cycle 12. The IWG/ELN criteria: CR (complete remission), PR (partial remission), Clinical improvement, Anemia response, Spleen response, Symptoms response, PD (progressive disease), SD (stable disease), Relapse, Cytogenetic remission, and Molecular remission

bone marrow fibrosis grade at the end of Cycle 6 and 12. Bone marrow fibrosis (MF) is graded as MF-0 to MF-3, with higher number indicating more disease.

MF-SAFv4.0,each of the items are scored 0 to 10, with total summation from 0 to 100, with higher score indicating more symptoms.

EORTC QLQ-C30, 28 item scored from 1 (not at all) to 4 (very much), and 2 items scored 1 (very poor) to 7 (excellent). Total score from 28 - 126, with higher score indicating poorer health

Formation Biologics

National Cancer Institute (NCI)

Myeloproliferative Neoplasm Research Consortium (MPN-RC)

John Mascarenhas

Associate Professor

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Neuroendocrine Tumor

Pancreatic Neuroendocrine Tumor

Neuroepithelioma

Pharmaceutical Solutions

All Drugs and Chemicals

Hematinics

Somatostatin

Liver Extracts

Lutetium Lu 177 dotatate

Radiopharmaceuticals

Patients will undergo a routine 68Ga-DOTATATE PET/CT. Patients with sufficient tumor uptake will be offered therapy with 177Lu-DOTATATE. The treatment regimen will consist of four administrations of 177Lu-DOTATATE-two intra-arterial followed by two intravenous, two months apart (+/- 2 weeks), with renal protective amino acid solution co-administration.

The treatment regimen will consist of four administrations of 177Lu-DOTATATE-two intra-arterial followed by two intravenous, two months apart (+/- 2 weeks), with renal protective amino acid solution co-administration. The activity per cycle will be fixed for each patient: patients will receive two intra-arterial cycles of 7.4 GBq, unless toxicity occurs requiring dose modifications.

177Lu-DOTATATE

Lisa Bodei, MD, PhD

This study will look at whether it is practical and safe to give Lutathera directly into an artery of the liver (hepatic intraarterial infusion). The researchers will compare the effects of hepatic intraarterial infusion in the liver with the effects of the standard approach (intravenous infusion in the arm). The researchers will also determine whether Lutathera is effective against participants' cancer.

This is an early-phase trial in which a total of 10 patients with progressive, inoperable, liver-dominant, metastatic GEP, bronchial or unknown primary NETs will be enrolled in this combined intraarterial/intravenous therapeutic approach with 177Lu-DOTATATE.

Lutathera in People With Gastroenteropancreatic (GEP), Bronchial or Unknown Primary Neuroendocrine Tumors That Have Spread to the Liver

A Pilot Study Investigating Intrahepatic Arterial And Intravenous Infusion Of The Radiolabeled Somatostatin Agonist 177Lu-DOTATATE In Patients With Liver-Dominant Metastatic Gastroenteropancreatic (GEP), Bronchial or Unknown Primary Well Differentiated Neuroendocrine Tumors

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Feasibility will be defined as at least 7 or more patients out of 10 patients who successfully complete 2 IA injections.

classified according to RECIST 1.1 criteria

Memorial Sloan Kettering Cancer Center

Nervous System Diseases

Cancer Pain

Pain

Breakthrough Pain

Neurologic Manifestations

Adjuvants, Anesthesia

Analgesics

Central Nervous System Depressants

Fentanyl

Analgesics, Opioid

Breakthrough pain control by bolus based IV patient-controlled anagesia Fentanyl bolus = MME \* 15%

Breakthrough pain control by sublingual fentanyl Fentanyl 100mcg/200mcg/300mcg according to the around-the-clock opioid requirement.

IV PCA(fentanyl) Fentanyl bolus = MME \* 15%

subligual fentanyl(Narco®) Fentanyl 100mcg/200mcg/300mcg according to the around-the-clock opioid requirement.

Sublingual Tablet

Jee Youn Moon, MD, PhD

Proportional dose of sublingual fentanyl tablet (Narco®) based on daily opioid requirement versus intravenous PCA for breakthrough cancer pain: A prospective, randomized, open-label, noninferiority trial.

Based on the previous around-the-clock analgesic demand compared to IV PCA in cancer pain patients to prepare the basis for the administration of fentanyl sublingual tablets with an initial dose.

Proportional Dose of Sublingual Fentanyl Tablet Based on Daily Opioid Requirement

Proportional Dose of Sublingual Fentanyl Tablet Based on Daily Opioid Requirement Versus Intravenous PCA for Breakthrough Cancer Pain: A Prospective, Randomized, Open Label, Non Inferiority Trial

Change in pain score compared to baseline Score '0' representing one pain extreme (e.g. "no pain") to '10' representing the other pain extreme (e.g. "pain as bad as you can imagine" or "worst pain imaginable"

sum of pain intensity change compared to baseline difference

number of additional doses fentanyl bolus or subligual

The severity of depression using Beck Depression Inventory(BDI) 1-10: These ups and downs are considered normal 11-16: Mild mood disturbance 17-20: Borderline clinical depression 21-30: Moderate depression 31-40: Severe depression over 40: Extreme depression

Satisfaction check using 5 Likert-scale

(1) Very dissatisfied; (2) Not satisfied; (3) Neutral; (4) Satisfied; (5) Very satidfied

Seoul National University

Dose Escalation Group: CPI-200 will be administered via intravenous infusion once every 3 weeks for up to 7 dose levels using an accelerated titration method followed by a conventional 3 + 3 study design

Dose Expansion Group: Maximum tolerated dose or the recommended Phase 2 dose (RP2D) from dose escalation group

CPI-200 will be administered via intravenous infusion on Day 1 of a 21-Day cycle

CPI-200

This is a prospective, open-label, single arm, non-randomized study of CPI-200 in patients with advanced tumors. CPI-200 is administered via intravenous infusion using an accelerated titration method followed by a conventional 3 + 3 study design to identify the maximum tolerated dose (MTD)

Primary Objectives:

• To determine the safety, tolerability and maximum tolerated dose (MTD) of CPI-200 in patients with advanced tumors

Secondary Objectives:

* To evaluate the pharmacokinetics (PK) of CPI-200
* To evaluate clinical response and resolution of symptoms after CPI-200 treatment
* To characterize adverse events of CPI-200 in patients with advanced cancers

Up to 7 dose levels of CPI-200 will be tested using an accelerated titration method followed by a conventional 3 + 3 dose escalation study design. MTD will be defined as the dose associated with a dose limiting toxicity (DLT) in less than or equal to 33% of patients at the dose level tested. Dose limiting toxicity (DLT) is defined as one of the following events occurring from the intravenous injection of CPI-200 within 21 days:

* All Grade 4 or greater adverse events as determined by CTCAEv5 criteria, excluding toxicities clearly related to disease progression or inter-current illness
* Any Grade 3 or greater non-hematologic, non-dermatologic toxicity with the exception of Grade 3 nausea, vomiting or diarrhea if lasting less than 72 hours, alopecia, or Grade 3 fatigue if lasting less than 7 days as determined by CTCAEv5 criteria
* Grade 3 thrombocytopenia in the presence of bleeding
* Grade 3 or greater febrile neutropenia
* Any hematologic or non-hematologic adverse events or abnormal laboratory value(s) related to CPI-200 that result(s) in permanent study discontinuation of study treatment

Accelerated titration method followed by a conventional 3 + 3 study design

Study of CPI-200 in Patients With Advanced Tumors

A Phase 1, First-in-Human Study Evaluating the Safety, Tolerability, and Pharmacokinetics of CPI-200 Via Intravenous Infusion in Patients With Advanced Solid Tumors

The data will not be shared due to confidentiality agreements.

• To determine the maximum tolerated dose (MTD), which is defined as the dose level at which fewer than 33% of patients experience a dose limiting toxicity (DLT) using a 3+3 strategy as assessed by CTCAE

• To assess clinical benefit by response rate and resolution of symptoms, which will be reported as response rate (%) of participants

• To assess adverse effect as either treatment-related or non-treatment-related as defined by CTCAE, which will be reported as % of participants

• To evaluate maximum plasma concentration (Cmax) of CPI-200 in patients tested

• To evaluate area under the curve (AUC) of CPI-200 in patients tested

Antineoplastic Agents

Capecitabine

Antimetabolites

Dose Escalation Groups:

CPI-100 will be administered via intravenous infusion once every 2 weeks (Q2W) for up to 5 dose levels and once every 3 weeks (Q3W Arm A) for up to 4 dose levels in a 3 + 3 dose escalation study

Dose Expansion Group: Maximum tolerated dose or the recommended Phase 2 dose (RP2D) from dose escalation group

CPI-100 will be administered via intravenous infusion once every 3 weeks in combination with oral capecitabine for up to 4 dose levels in a dose escalation study (Q3W Arm B)

CPI-100 will be administered via intravenous infusion on Day 1 of a 14-Day cycle

CPI-100

Capecitabine will be administered 1000 mg/m2 orally twice a day for 2 weeks followed by a 7-day rest period

This is a prospective, open-label, 2-arm, non-randomized study of CPI-100 in patients with advanced tumors. CPI-100 is administered via intravenous infusion in a 3 + 3 study design to identify the maximum tolerated dose (MTD).

Primary Objectives:

• To determine the safety, tolerability and maximum tolerated dose (MTD) of CPI-100 as once every two weeks (Q2W) and once every three weeks (Q3W) regimens in patients with advanced tumors

Secondary Objectives:

* To evaluate the pharmacokinetics (PK) of CPI-100
* To evaluate clinical response and resolution of symptoms after CPI-100 treatment
* To characterize adverse events of CPI-100 monotherapy and CPI-100 in combination with capecitabine in patients with advanced cancers

Up to 5 dose levels of CPI-100 Q2W, 4 dose levels of Q3W regimen of CPI-100 monotherapy (Q3W Arm A) and 4 dose levels of Q3W regimen of CPI-100 in combination with capecitabine (Q3W Arm B) will be tested in a dose escalation study. MTD will be defined as the dose associated with a dose limiting toxicity (DLT) in less than or equal to 33% of patients at the dose level tested. Dose limiting toxicity (DLT) is defined as one of the following events occurring from the intravenous injection of CPI-100 within 28 days (Q2W) or 42 days (Q3W):

* Grade 4 or greater treatment related adverse events
* Any Grade 3 or greater treatment related non-hematologic, non-dermatologic toxicity (including nausea, vomiting or diarrhea lasting more than 72 hours)

Study of CPI-100 in Patients With Advanced Tumors

A Phase 1, First-in-Human Study Evaluating the Safety, Tolerability, and Pharmacokinetics of CPI-100 Via Intravenous Infusion in Patients With Advanced Solid Tumors

The data will not be shared due to confidentiality agreements

• To determine the maximum tolerated dose (MTD), which is defined as the dose level at which fewer than 33% of patients experience a dose limiting toxicity (DLT) using a 3+3 strategy as assessed by CTCAE5

• To assess clinical benefit by response rate and resolution of symptoms, which will be reported as response rate (%)

• To assess adverse effect as either treatment-related or non-treatment-related as defined by CTCAE

• To evaluate maximum plasma concentration (Cmax) of CPI-100 in patients tested

• To evaluate area under the curve (AUC) of CPI-100 in patients tested

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase I Study of CPI-300 in Patients With Advanced Tumors	NCT04808453	Advanced Tumors	CPI-300	18 Years -	Coordination Pharmaceuticals, Inc.
A Clinical Study of 6MW3211 Injection in the Treatment of Advanced Malignant Neoplasm	NCT05048160	Advanced Malign...	Intravenous Inf...	18 Years -	Mabwell (Shanghai) Bioscience Co., Ltd.
6MW3511 in Patients With Advanced Solid Tumor	NCT05524194	Solid Tumors	Intravenous Inf...	18 Years - 80 Years	Mabwell (Shanghai) Bioscience Co., Ltd.
MPN-RC 118 AVID200 in Myelofibrosis	NCT03895112	Primary Myelofi... Post-essential ... Post-polycythem... Post ET MF Post PV MF	AVID200	18 Years -	Icahn School of Medicine at Mount Sinai
Lutathera in People With Gastroenteropancreatic (GEP), Bronchial or Unknown Primary Neuroendocrine Tumors That Have Spread to the Liver	NCT04544098	Neuroendocrine ... Liver-Dominant ...	177Lu-DOTATATE	18 Years -	Memorial Sloan Kettering Cancer Center
Lutathera in People With Gastroenteropancreatic (GEP), Bronchial or Unknown Primary Neuroendocrine Tumors That Have Spread to the Liver	NCT04544098	Neuroendocrine ... Liver-Dominant ...	177Lu-DOTATATE	18 Years -	Memorial Sloan Kettering Cancer Center
Proportional Dose of Sublingual Fentanyl Tablet Based on Daily Opioid Requirement	NCT05053308	Cancer Pain Breakthrough Pa...	Intravenous Inf... Sublingual Tabl...	19 Years - 80 Years	Seoul National University
Study of CPI-200 in Patients With Advanced Tumors	NCT03953742	Advanced Solid ...	CPI-200	18 Years -	Coordination Pharmaceuticals, Inc.
Study of CPI-100 in Patients With Advanced Tumors	NCT03781362	Advanced Tumors	CPI-100 Capecitabine	18 Years -	Coordination Pharmaceuticals, Inc.

Spots Global Cancer Trial Database for intravenous infusion