Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Nervous System Diseases

Rare Diseases

Melanoma

Neoplasm Metastasis

Brain Neoplasms

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neoplastic Processes

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

HBI-8000 30 mg oral BIW + nivolumab IV at specific doses on specific days

Placebo oral BIW + nivolumab IV at specific doses on specific days

Patients will take 30 mg of HBI-8000 orally approximately 30 minutes after a full meal, beginning on Day 1 and continue every 3 to 4 days on the BIW schedule. On Day 1 of each cycle nivolumab IV will be administered by intravenous infusion at specific doses on specific days in accordance with OPDIVO® manufacturer regional product information insert and the institution's prescribing practice. In adolescent patients with body weight \< 40 kg, nivolumab will be dosed at specific doses on specific days.

HBI-8000 in combination with nivolumab

Patients will take 30 mg of Placebo orally approximately 30 minutes after a full meal, beginning on Day 1 and continue every 3 to 4 days on the BIW schedule. On Day 1 of each cycle nivolumab IV at specific doses will be administered by intravenous infusion in accordance with OPDIVO® manufacturer regional product information insert and the institution's prescribing practice.

Placebo in combination with nivolumab

M Tawashi

Nina Singh

Susan Poechhacker

Hong Shue, M.D.

Agnieszka Malczewski, M.D.

Virginia Murphy

Donna McIntyre

Sharad Sharma, MD

Carole Mott

Myron Klevansky, MD

Medical Oncology Clinical Trials Unit

Bavanthi Balkrishnar

Nursing

C Gedye, MD

John T Ning, MD, PhD

This is a phase 3 study to compare the efficacy and safety of HBI-8000 or Placebo combined with nivolumab on patients with unresectable or metastatic melanoma and eligible patients who are not adolescents or patients with new, progressive brain metastasis will be stratified by PD-L1 expression and LDH level.

This is a multicenter, randomized, double-blind, placebo-controlled Phase 3 study of HBI-8000 or Placebo combined with nivolumab. Randomization of eligible patients will be stratified by PD-L1 expression (positive, ≥1% expression level versus negative, \<1% expression level) and LDH (normal versus elevated) in the main study. Adults with new, progressive brain metastasis, or adolescents with or without new progressive brain metastasis will be enrolled in a separate, non-randomized, open-label cohort to receive the combination of HBI-8000 and nivolumab.

In the main study, eligible patients will be randomized within the appropriate stratum at a 1:1 ratio to the Test arm or the Control arm. Study treatment will be initiated within 3 days of randomization.

A treatment cycle consists of 28 days. Patients will be treated with one of the following:

Test arm: HBI-8000 30 mg oral BIW + nivolumab IV at specific doses on specific days

Control arm: Placebo oral BIW + nivolumab IV at specific doses on specific days

The Study Treatment (HBI-8000 or Placebo) is administered approximately 30 minutes after a full meal.

The Study Treatment (HBI-8000 or Placebo) will be administered twice a week on the following days of every 28-day cycle:

* CxW1: Days 1, 4
* CxW2: Days 8, 11
* CxW3: Days 15, 18
* CxW4: Days 22, 25

Study treatment must commence within 3 days after randomization and continue up to 2 years or until disease progression (confirmed), unacceptable toxicity or patient withdrawal of consent.

In addition to Study Treatment, nivolumab is administered at specific doses on specific days as an intravenous infusion over approximately 30 minutes. Nivolumab will be administered on Day 1 of each cycle.

For non-randomized cohort for special population, eligible subjects will receive HBI-8000 30 mg oral BIW and nivolumab IV at specific doses on specific days, under the same schedule as described above. For adolescents weighing \< 40 kg, nivolumab will be dosed at specific doses every 4 weeks. Nivolumab will be administered on Day 1 of each cycle.

This is a double-blind, placebo-controlled Phase 3 study of HBI-8000 or Placebo combined with nivolumab.

All Eligible patients will be randomized within the appropriate stratum at a 1:1 ratio to the Test arm or the Control arm, with the exception of Cohort for special population.

Study Comparing Investigational Drug HBI-8000 Combined With Nivolumab vs. Nivolumab in Patients With Advanced Melanoma

A Multicenter, Randomized, Double-Blind Phase 3 Study of HBI-8000 Combined With Nivolumab Versus Placebo With Nivolumab in Patients With Unresectable or Metastatic Melanoma Not Previously Treated With PD-1 or PD-L1 Inhibitors

Duration of Response (DoR) defined as the time from the first date of PR or better as determined by BIRC to the first date of PD or death from any cause.

Disease Control Rate (DCR) defined as the percentage of patients enrolled in each study arm with best overall response of CR, PR or stable disease (SD) as determined by BIRC.

Objective Response Rate (ORR) defined as the percentage of patients enrolled in each study arm with a best response of Complete Response (CR) or Partial Response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1), as determined by the blinded independent review committee (BIRC).

Progression-free Survival (PFS) defined as the time from the date of randomization to the first date of documented disease progression as determined by BIRC, or the date of death due to any cause, whichever occurs first.

Overall Survival (OS) defined as the time from date of randomization to the date of death due to any cause.

Safety defined as incidence rate of adverse events (AEs), severity (CTCAE v.5.0), causal relationship assessment, and outcomes of reported AEs.

Bristol-Myers Squibb

HUYABIO International, LLC.

Dose Escalation: Subjects will be administered orally at 140mg, 160mg, 180mg, 220mg, QD during the study, until disease progression or intolerable toxicity.

Dose Expansion: Subjects with unresectable or metastatic melanoma will be administered orally at recommended phase II dose from phase Ib once daily during the study, until disease progression or intolerable toxicity.

ST-1898 tablets

Jun GUO, MD

Chuanliang CUI, MD

ST-1898 is a receptor tyrosine kinase (RTK) inhibitor for multi-targets, especially for VEGFR2, c-MET, AXL, PDGFRA, RET, KIT etc. This trial is to evaluate its safety, tolerability, pharmacokinetic, and efficacy in subjects with unresectable or metastatic melanoma.

In phase Ib, the primary objectives are to assess the safety and tolerability, and to determine Recommended Phase 2 dose (RP2D) of ST-1898 tablets in subjects with unresectable or metastatic melanoma. Secondary objectives are to assess the plasma concentration of ST-1898 and to evaluate the efficacy.

In phase II, the primary objective is to assess the anti-tumor activities of ST-1898 tablets in subjects with unresectable or metastatic melanoma. The secondary objective is to evaluate the safety of ST-1898 tablets.

A Study of ST-1898 for Unresectable or Metastatic Melanoma

A Phase Ib/II Study to Evaluate the Efficacy and Safety of ST-1898 in Subjects With Unresectable or Metastatic Melanoma

AEs and SAEs will be assessed according to the National Cancer Institute (NCI) CTCAE v5.0

RP2D was determined according to MTD. MTD was defined as the highest dose level at which no more than 1 in 6 participants experienced a dose-limiting toxicity (DLT) during the first cycle (21days) of treatment.

ORR is defined as the percentage of participants who experience a CR or PR based on RECIST 1.1 (CR: Complete Response, Disappearance of all target lesions, PR: Partial Response, At least a 30% decrease in the sum of diameters of target lesions)

To assess plasma pharmacokinetics (PK) of oral administration of ST-1898

Objective Response Rate (ORR) per RECIST 1.1

Progression-Free Survival (PFS) per RECIST 1.1

DoR Duration of Response (DoR) per RECIST 1.1

Disease Control Rate (DCR) per RECIST 1.1

The AEs and SAEs will be assessed according to the National Cancer Institute (NCI) CTCAE v5.0.

To assess plasma Trough concentration of oral administration of ST-1898 in subjects with unresectable or metastatic melanoma

To assess plasma Peak concentration of oral administration of ST-1898 in subjects with unresectable or metastatic melanoma

Beijing Scitech-Mq Pharmaceuticals Limited

Pharmaceutical Solutions

Paclitaxel

Carboplatin

Albumin-Bound Paclitaxel

Dacarbazine

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Alkylating

Alkylating Agents

BMS-936558 3 mg/kg solution for injection by intravenous (IV), every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

Dacarbazine: 1000mg/m2, Powder for IV solution, IV, every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

Carboplatin: Area under the concentration-time curve (AUC) 6, solution for injection, IV, every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

Paclitaxel: 175 mg/ m2, solution for injection, IV, every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

BMS-936558

The purpose of the study is to estimate the response rate and compare overall survival of patients taking BMS-936558 to those taking study physician's choice of either Dacarbazine or Carboplatin and Paclitaxel

A Study to Compare BMS-936558 to the Physician's Choice of Either Dacarbazine or Carboplatin and Paclitaxel in Advanced Melanoma Patients That Have Progressed Following Anti-CTLA-4 Therapy (CheckMate 037)

A Randomized Open-Label Phase 3 Trial of BMS-936558 (Nivolumab) Versus Investigator's Choice in Advanced (Unresectable or Metastatic) Melanoma Patients Progressing Post Anti-CTLA-4 Therapy

Objective response rate (ORR) per Independent Review Committee (IRC) is defined as the number of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of randomized participants using RECIST 1.1

Overall Survival (OS) was defined the time between the date of randomization to the date of death. For participants without documentation of death, OS was censored on the last date the participant was known to be alive. Unit of measure (months) is the median survival time.

Progression Free Survival (PFS) is defined as the time from randomization to the date of the first documented progression, as determined by the Independent Review Committee (IRC) using RECIST 1.1, or death due to any cause, whichever occurs first. Participants who died without a reported progression were considered to have progressed on the date of their death. Participants who did not progress or die were censored on the date of their last evaluable tumor assessment before subsequent anti-cancer therapy. Unit of measure (months) is the median survival time.

Objective Response Rate (ORR) is defined as the number of participants with a Best Overall Response (BOR) of complete response (CR) or partial response (PR) divided by number of randomized participants. PD-L1 expression evaluated for ORR.

Overall Survival (OS) by PD-L1 expression was defined the time between the date of randomization to the date of death. For participants without documentation of death, OS was censored on the last date the participant was known to be alive.

Health-related Quality of Life (HRQoL) was assessed with the EORTC QLQ-C30 questionnaire, which is the most commonly used quality-of-life instrument in oncology trials. The instrument's 30 items were divided among 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, pain, nausea/vomiting, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties), and a global health/quality of life scale. Raw scores for the EORTC QLQ-C30 were transformed to a 0-100 metric.

Higher scores for all functional scales and Global Health Status=better HRQoL Increase from baseline indicates improvement in HRQoL. Lower scores for symptom scales=better HRQoL Decline from baseline for symptom scales =improvement in symptoms compared to baseline.

A 10 point difference on a 100 point scale between treatments was considered clinically significant.

Dacarbazine: 1000 mg/m\^2 IV over 30 to 60 minutes Q3W, or Carboplatin: Area under the concentration-time curve (AUC) 6 IV over 30 minutes Q3W, and Paclitaxel: 175 mg/m\^2 IV over 180 minutes Q3W

Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel)

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

White

Black or African American

Asian

American Indian or Alaska Native

Native Hawaiian or Other Pacific Islander

Other

Race/Ethnicity, Customized

Bristol-Myers Squibb Study Director

Objective Response Rate (ORR)

Hazard Ratio is Nivolumab 3 mg/kg (IV) over Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel)

Dacarbazine: 1000 mg/m\^2 IV Q3W Carboplatin: Area under the concentration-time curve (AUC) 6 IV Q3W Paclitaxel: 175 mg/m\^2 IV Q3W

Overall Survival (OS)

Progression Free Survival (PFS)

For \<5% PD-L1 expression. Ratio of Nivolumab over Investigator's Choice

For \>=5% PD-L1 expression. Ratio of Nivolumab over Investigator's Choice

<5% PD-L1 expression

>=5% PD-L1 expression

Objective Response Rate (ORR) by Baseline PD-L1 Expression

All PD-L1 positive evaluable participants for OS

Overall Survival (OS) by PD-L1 Positive

All PD-L1 negative evaluable participants for OS

Overall Survival (OS) by PD-L1 Negative

Physical Functioning Follow-Up 1

Physical Functioning Follow-Up 2

Role Functioning Follow-Up 1

Role Functioning Follow-Up 2

Emotional Functioning Follow-Up 1

Emotional Functioning Follow-Up 2

Cognitive Functioning Follow-Up 1

Cognitive Functioning Follow-Up 2

Social Functioning Follow-Up 1

Social Functioning Follow-Up 2

Global Health Status Follow-Up 1

Global Health Status Follow-Up 2

Dyspnea Follow-Up 1

Dyspnea Follow-Up 2

Insomnia Follow-Up 1

Insomnia Follow-Up 2

Apatite loss Follow-Up 1

Apatite loss Follow-Up 2

Constipation Follow-Up 1

Constipation Follow-Up 2

Diarrhea Follow-Up 1

Diarrhea Follow-Up 2

Financial Difficulties Follow-Up 1

Financial Difficulties Follow-Up 2

Fatigue Follow-Up 1

Fatigue Follow-Up 2

Nausea and Vomiting Follow-Up 1

Nausea and Vomiting Follow-Up 2

Pain Follow-Up 1

Pain Follow-Up 2

Mean Change From Baseline in Health-related Quality of Life (HRQoL)

Pre-Treatment

Treatment

Ipilimumab

Nivolumab 3 mg/kg solution intravenously every 2 weeks plus Placebo matching with Ipilimumab 0 mg/kg solution intravenously on weeks 1, 4 and Placebo matching with Nivolumab on weeks 4 for cycles 1 and 2, until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

Nivolumab 1 mg/kg solution intravenously combined with Ipilimumab 3 mg/kg solution intravenously every 3 weeks for 4 doses then Nivolumab 3 mg/kg solution intravenously every 2 weeks plus Placebo matching with Nivolumab on weeks 3 and 5 for cycles 1 and 2, until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

Ipilimumab 3 mg/kg solution intravenously every 3 weeks for a total of 4 doses plus Placebo matching with Nivolumab 0 mg/kg solution intravenously on weeks 3 and 5 for cycles 1 and 2, until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends (Placebo matching with Nivolumab is no longer required)

Placebo for Nivolumab

Placebo for Ipilimumab

The purpose of this study is to show that Nivolumab and/or Nivolumab in combination with Ipilimumab will extend progression free survival and overall survival compared to Ipilimumab alone.

Phase 3 Study of Nivolumab or Nivolumab Plus Ipilimumab Versus Ipilimumab Alone in Previously Untreated Advanced Melanoma (CheckMate 067)

A Phase 3, Randomized, Double-Blind Study of Nivolumab Monotherapy or Nivolumab Combined With Ipilimumab Versus Ipilimumab Monotherapy in Subjects With Previously Untreated Unresectable or Metastatic Melanoma

PFS was defined as the time between the date of randomization and the first date of documented progression, as determined by the Investigator, or death due to any cause, whichever occurred first. Progression is defined, using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, and an absolute increase of at least 5 mm. Participants who died without a reported progression were considered to have progressed on the date of their death. Participants who did not progress or die were censored on the date of their last evaluable tumor assessment. Participants who did not have any on study tumor assessments and did not die were censored on their date of randomization. Participants who started anti-cancer therapy without prior reported progression were censored on the date of their last evaluable tumor assessment prior to the initiation of subsequent anti-cancer therapy.

OS was defined as the time between the date of randomization and the date of death. For participants without documentation of death, OS was censored on the last date the participant was known to be alive.

OS was defined as the time between the date of randomization and the date of death. For participants without documentation of death, OS was censored on the last date the participant was known to be alive. The overall survival rate at time T (6, 12, or 24 months) was defined as the probability that a participant was alive at time T following randomization.

PFS was defined as the time between the date of randomization and the first date of documented progression, as determined by the Investigator, or death due to any cause, whichever occurred first. Participants who died without a reported progression were considered to have progressed on the date of their death. Participants who did not progress or die were censored on the date of their last evaluable tumor assessment. Participants who did not have any on study tumor assessments and did not die were censored on their date of randomization. Participants treated beyond progression were considered to have progressive disease at the time of the initial progression event regardless of subsequent tumor response. Participants who started anti-cancer therapy without a prior reported progression were censored on the date of their last evaluable tumor assessment prior to the initiation of subsequent anti-cancer therapy.

PFS data is presented as it was in Primary Outcome Measure #1. The statistical analysis following this outcome measure (#5) reports on a secondary objective comparing PFS between the Nivolumab and Nivolumab + Ipilimumab arms.

OS data is presented as it was in Primary Outcome Measure #2. The statistical analysis following this outcome measure (#6) reports on a secondary objective comparing OS between the Nivolumab and Nivolumab + Ipilimumab arms.

The ORR was defined as the number of participants with a best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized participants for each arm. The BOR was defined as the best response designation, as determined by the Investigator, recorded between the date of randomization and the date of progression, as assessed by the Investigator per RECIST 1.1 or the date of subsequent anticancer therapy (including tumor-directed radiotherapy and tumor-directed surgery), whichever occurred first. For participants without evidence of RECIST 1.1 progression or subsequent anticancer therapy, all available response designations contributed to the BOR assessment. CR= Disappearance of all evidence of disease, confirmed by PET scan; PR= Regression of measureable disease and no new sites; Stable Disease (SD)= Failure to attain CR/PR or PD; Progressive Disease (PD)= Any new lesion or increase by \>=50% of previously involved sites from nadir.

PD-L1 expression was defined as the percent of tumor cells demonstrating plasma membrane PD-L1 staining of any intensity using an IHC assay. Tumor biopsy specimens without measurable PD-L1 expression were classified as indeterminate if the staining was hampered for reasons attributed to the biology of the specimen and not because of improper specimen preparation or handling. Missing specimens, specimens that were not optimally collected (ie not evaluable), and all other specimens were classified as unknown. Participants must have been classified as PD-L1 \>=5% or PD-L1 \<5% per a verified IHC assay, or as indeterminate (ie not unknown), in order to be randomized.

Health Related Quality of Life was assessed using the EORTC QLQ-C30 questionnaire Version 3. With the exception of 2 items included in the global health/quality of life scale, for which responses range from 1 (Very poor) to 7 (Excellent), item responses range from 1 (Not at all) to 4 (Very much). Raw scores for the EORTC QLQ-C30 are transformed to a 0-100 metric such that higher scores for all functional scales and Global Health Status indicate better HRQoL; an increase from baseline indicates improvement in HRQoL compared to baseline. The mean score for all participants in an arm at a given week was subtracted from the mean score of the participants in that arm at baseline. Mean changes from baseline score is presented for all participants in an arm that remained on treatment and completed the EORTC-QLQ-C30 questionnaire at that time point.

Health Related Quality of Life was assessed using the EORTC QLQ-C30 questionnaire Version 3. With the exception of 2 items included in the global health/quality of life scale, for which responses range from 1 (Very poor) to 7 (Excellent), item responses range from 1 (Not at all) to 4 (Very much). Raw scores for the EORTC QLQ-C30 are transformed to a 0-100 metric such that higher scores for all functional scales and Global Health Status indicate better HRQoL; an increase from baseline indicates improvement in HRQoL compared to baseline.

Nivolumab monotherapy 3 mg/kg intravenous (IV) once every 2 weeks (Q2W) until disease progression or unacceptable toxicity

NIVOLUMAB

Nivolumab 1 mg/kg IV combined with Ipilimumab 3 mg/kg IV once every 3 weeks (Q3W) for 4 doses followed by nivolumab 3 mg/kg IV Q2W until disease progression or unacceptable toxicity

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study Comparing Investigational Drug HBI-8000 Combined With Nivolumab vs. Nivolumab in Patients With Advanced Melanoma	NCT04674683	Unresectable or... Progressive Bra...	HBI-8000 in com... Placebo in comb...	12 Years -	HUYABIO International, LLC.
A Study of ST-1898 for Unresectable or Metastatic Melanoma	NCT06359860	Unresectable or...	ST-1898 tablets	18 Years -	Beijing Scitech-Mq Pharmaceuticals Limited
A Study to Compare BMS-936558 to the Physician's Choice of Either Dacarbazine or Carboplatin and Paclitaxel in Advanced Melanoma Patients That Have Progressed Following Anti-CTLA-4 Therapy (CheckMate 037)	NCT01721746	Unresectable or...	BMS-936558 Dacarbazine Carboplatin Paclitaxel	18 Years -	Bristol-Myers Squibb
A Study to Compare BMS-936558 to the Physician's Choice of Either Dacarbazine or Carboplatin and Paclitaxel in Advanced Melanoma Patients That Have Progressed Following Anti-CTLA-4 Therapy (CheckMate 037)	NCT01721746	Unresectable or...	BMS-936558 Dacarbazine Carboplatin Paclitaxel	18 Years -	Bristol-Myers Squibb
Phase 3 Study of Nivolumab or Nivolumab Plus Ipilimumab Versus Ipilimumab Alone in Previously Untreated Advanced Melanoma (CheckMate 067)	NCT01844505	Unresectable or...	Nivolumab Ipilimumab Placebo for Niv... Placebo for Ipi...	18 Years -	Bristol-Myers Squibb
Prolgolimab 250 mg Q3W in Patients With Unresectable or Metastatic Melanoma	NCT05783882	Unresectable or...	Prolgolimab	18 Years -	Biocad
A Study to Compare BMS-936558 to the Physician's Choice of Either Dacarbazine or Carboplatin and Paclitaxel in Advanced Melanoma Patients That Have Progressed Following Anti-CTLA-4 Therapy (CheckMate 037)	NCT01721746	Unresectable or...	BMS-936558 Dacarbazine Carboplatin Paclitaxel	18 Years -	Bristol-Myers Squibb

Spots Global Cancer Trial Database for unresectable or metastatic melanoma