Neoplasms

All Conditions

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Antirheumatic Agents

Gemcitabine

Paclitaxel

Hydroxychloroquine

Albumin-Bound Paclitaxel

Immunomodulating Agents

Nivolumab

Ipilimumab

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Antimalarials

Antiprotozoal Agents

Antiparasitic Agents

Enzyme Inhibitors

Nivolumab will be administered intravenously at 360 mg every 3 weeks for up to 2 years.

Nivolumab (Cohort A)

For Cohort A and B, ipilimumab will be administered intravenously at 1mg/kg every 6 weeks for up to 2 cycles. For Cohort C, ipilimumab will be administered intravenously at 1mg/kg on C2D1 and C4D1.

Ipilimumab (Cohort A, B and C)

Hydroxychloroquine will be administered orally daily for up to 2 years.

Hydroxychloroquine (HCQ) (Cohort B)

Nab-paclitaxel will be administered intravenously at 125 mg/m2 for 2 weeks on and 1 week off, for at least 24 weeks, unless treatment discontinuation criteria are met.

Nab-paclitaxel (nP) (Cohort A, B and C)

Gemcitabine will be administered intravenously at 1000 mg/m2 for 2 weeks on and 1 week off, for at least 24 weeks, unless treatment discontinuation criteria are met.

Gemcitabine (gem) (Cohort A, B and C)

NG-350A will be administered intravenously on Cycle 1 Days 15 (1e12 viral particles), 17 (3e12 viral particles), and 19 (3e12 viral particles).

NG350A (Cohort C)

Parker Institute for Cancer Immunotherapy

This trial is designed to evaluate multiple clinical hypotheses and mechanistically-defined combinations to evaluate the safety and efficacy of first-line chemo-immunotherapy combinations in participants with metastatic pancreatic ductal adenocarcinoma (mPDAC).

This is an open-label, non-randomized, exploratory platform trial designed to assess the safety and antitumor activity of immunotherapy, in combination with standard of care chemotherapy, in participants with mPDAC who have not received prior therapy. Where supportive mechanistic data are available, immunotherapy may also be combined with other treatment modalities (eg, radiation). Each cohort of this platform trial will test a different immunotherapy combination and consist of up to 2 stages: an initial stage (Stage 1) to evaluate safety, biomarkers, and/or clinical activity of the combination and an expanded cohort (Stage 2), when warranted, based on the safety, clinical activity, and/or biomarker results from Stage 1. The Sponsor intends to modify and/or add new combinations to the protocol as data emerge from scientific findings, in this and other trials.

This trial will be conducted in participants with histologically or cytologically documented diagnosis of mPDAC, with measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, who have not received prior systemic therapy for their disease in the metastatic setting. Participants must have adequate organ and hematologic function and acceptable performance status. Participants must consent to tumor biopsies, including a pre-treatment (baseline) and on-treatment samples.

Exploratory Platform Trial to Evaluate Immunotherapy Combinations With Chemotherapy for the Treatment of Patients With Previously Untreated Metastatic Pancreatic Adenocarcinoma

A Multicenter, Open-label, ExploRatory Platform Trial to EValuate ImmunOtherapy Combinations With Chemotherapy for the Treatment of Patients With PreviousLy UnTreated MetastatIc Pancreatic AdenOcarciNoma (REVOLUTION)

Defined as the proportion of participants who achieve a confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

Defined as the proportion of participants who achieve confirmed CR or PR or stable disease (SD) lasting at least 16 weeks

Defined as the time from first documentation of response (CR or PR) to first radiographic documentation of progressive disease (PD) or death due to any cause.

Defined as the time from initiation of study intervention to date of first documented radiographic progression of disease or death due to any cause.

Defined as the time from initiation of study intervention until death due to any cause.

Bristol-Myers Squibb

Cancer Research Institute, New York City

Akamis Bio

Cancer Insight, LLC

Skin and Connective Tissue Diseases

Breast Neoplasms

Triple Negative Breast Neoplasms

Breast Diseases

Skin Diseases

Bevacizumab

Antibodies

Immunoglobulins

If patients were triple-negative breast cancer with IM subtype and HER2-low-positive

If patients were triple-negative breast cancer with IM subtype and HER2-zero

If patients were triple-negative breast cancer with BLIS subtype and HER2-low-positive

If patients were triple-negative breast cancer with BLIS subtype and HER2-zero

If patients were triple-negative breast cancer with LAR subtype and HER2-low-positive

If patients were triple-negative breast cancer with LAR subtype and HER2-zero

If patients were triple-negative breast cancer with MES subtype and HER2-low-positive

If patients were triple-negative breast cancer with MES subtype and HER2-zero

A1: an anti-HER2 antibody-drug conjugate (ADC)

A1: SHR-A1811

A2: SHR-A1811: an anti-HER2 antibody-drug conjugate (ADC)

Camrelizumab: an anti-programmed death-1 (PD-1) antibody

A2: SHR-A1811 with Camrelizumab

B1: an Trophoblast cell-surface antigen 2 (TROP2) ADC

B1: TROP2 ADC

B2: TROP2 ADC : an Trophoblast cell-surface antigen 2 (TROP2) ADC

Camrelizumab: an anti-programmed death-1 (PD-1) antibody

B2: TROP2 ADC with Camrelizumab

C1: an anti-HER2 antibody-drug conjugate (ADC)

C1: SHR-A1811

C2: SHR-A1811: an anti-HER2 antibody-drug conjugate (ADC)

BP102: a humanized recombinant monoclonal IgG1 antibody (biosimilar to bevacizumab)

C2: SHR-A1811 with BP102

D1: an Trophoblast cell-surface antigen 2 (TROP2) ADC

D1: TROP2 ADC

D2: TROP2 ADC : an Trophoblast cell-surface antigen 2 (TROP2) ADC

BP102: a humanized recombinant monoclonal IgG1 antibody (biosimilar to bevacizumab)

D2: TROP2 ADC with BP102

E1: an anti-HER2 antibody-drug conjugate (ADC)

E1: SHR-A1811

F1: an Trophoblast cell-surface antigen 2 (TROP2) ADC

F1: TROP2 ADC

G1: an anti-HER2 antibody-drug conjugate (ADC)

G1: SHR-A1811

H1: an Trophoblast cell-surface antigen 2 (TROP2) ADC

H1: TROP2 ADC

Zhimin Shao, M.D.

Yin Liu, M.D.

This is a Phase II, open-label, Single-center platform study research based on molecular subtypes to explore precision therapy in refractory triple-negative breast cancer.

This is a Phase II, open-label, Single-center platform study，Based on FUSCC four TNBC subtypes and the results of the previous FUTURE trial, the investigators designed this platform trial, which for combined the TNBC subtyping and genomic sequencing-guided precision targeted therapy for refractory metastatic TNBC patients. In this trial, refractory mTNBC patients eligible for inclusion can be divided into various precision treatment group according to molecular typing and subtyping to evaluate the efficacy and safety of multiple precision targeted treatment. The research therapy arm can be updated with the update of basic translational research in our center, especially the refinement of typing, the discovery of new targets and the development of novel targeted drugs.

FUSCC Refractory TNBC Platform Study (FUTURE2.0)

Precision Platform Study of Refractory Triple-negative Breast Cancer Based on Molecular Subtyping（(A Phase II, Open-label, Single-center Platform Study）

The proportion of participants whose best outcome is complete remission or partial remission (according to RECIST1.1)

Time to progressive disease (according to RECIST1.1)

Duration of whose best outcome is complete remission or partial remission (according to RECIST1.1)

The proportion of patients with the best overall response of CR, PR, or stable disease (SD)

To evaluate the rate of adverse effects of patient by the standard CTCAE scale (V5.0)

Fudan University

Professor

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Neuroendocrine Tumor

Neuroepithelioma

Spartalizumab

Participnats randomized to receive LAG525 at a dosage of 600 mg administered intravenously every 4 weeks, in combination with PDR001 at a dosage of 400 mg administered intravenously every 4 weeks

Participants randomized to receive INC280 orally at a dosage of 400 mg twice daily, in combination with PDR001 intravenously at a dosage of 400 mg every 4 weeks

Participants randomized to receive to receive ACZ885 at a dosage of 300 mg administered subcutaneously every 4 weeks, in combination with PDR001 at a dosage of 400 mg administered intravenously every 4 weeks

Participants randomized to receive LEE011 orally at a dosage of 600 mg once daily on Days 1-21 of a 28-day cycle, in combination with PDR001 intravenously at a dosage of 400 mg every 4 weeks

LAG-3 positive participants received LAG525 at a dosage of 600 mg administered intravenously every 4 weeks, in combination with PDR001 at a dosage of 400 mg administered intravenously every 4 weeks

400 mg of PDR001 administered every 4 weeks intravenously

PDR001

600 mg of LAG525 administered every 4 weeks intravenously

LAG525

400 mg of INC280 administered twice daily orally

INC280

200 mg of ACZ885 administered every 4 weeks subcutaneosuly

ACZ885

600 mg of LEE011 orally taken once daily on Days 1-21 of a 28-day cycle

LEE011

Novartis Pharmaceuticals

The primary purpose of this study is to evaluate the efficacy of novel spartalizumab (PDR001) combinations in previously treated unresectable or metastatic melanoma

This study was a randomized, open-label, two-part, multi-center, open platform phase II study designed to evaluate the efficacy and safety of the anti-PD-1 antibody PDR001 in combination with novel agents for previously treated unresectable or metastatic melanoma. Additionally, a non-randomized single-arm was added based on interim analysis findings to assess the efficacy and safety of PDR001 in combination with LAG525 in subjects with previously treated unresectable or metastatic LAG-3 positive melanoma.

The study consisted of two parts: the selection part and the expansion part, which were applicable to both the randomized and non-randomized sections. In the randomized section, participants were randomized to one of four combination arms available for enrollment:

* Arm 1: LAG525 600 mg intravenously (i.v.) every 4 weeks (Q4W) and PDR001 400 mg i.v. Q4W.
* Arm 2: INC280 400 mg orally (p.o.) twice daily (BID) and PDR001 400 mg i.v. Q4W.
* Arm 3: ACZ885 300 mg subcutaneously (s.c.) every 4 weeks (Q4W) and PDR001 400 mg i.v. Q4W.
* Arm 4: LEE011 600 mg p.o. once daily (QD) on Days 1-21 of a 28-day cycle and PDR001 400 mg i.v. Q4W.

At each interim analysis, the following determinations were made: (1) which arm met the pre-specified efficacy criteria and expanded to the expansion part, (2) which arms continued enrollment in selection part (up to 45 subjects), and (3) which arms were discontinued due to futility, considering efficacy, safety, and biomarker data. The expansion phase included enrollment of subjects only in the combination arms that met the pre-specified criteria in selection part.

In the non-randomized section, a single combination arm was opened for enrollment in selection part:

• Arm 1A: LAG525 600 mg i.v. Q4W and PDR001 400 mg i.v. Q4W, assessed in a population selected based on the LAG-3 status of their tumor.

Arm 1A would be eligible for enrollment in expansion part only if it met the pre-specified criterion for this arm.

Participants received the study treatment corresponding to their assigned arm on a 28-day cycle basis until disease progression, as determined by local assessment using RECIST v1.1 criteria, or until certain events occurred, such as unacceptable toxicity, initiation of subsequent anti-cancer therapy, withdrawal of consent, investigator's decision, loss to follow-up, death, or termination of the study by the sponsor. Following discontinuation of the study treatment, all subjects were monitored for safety evaluations for up to 150 days after their last dose of the study treatment.

After approval of protocol amendment 5 (26Jun2020), a non-randomized single arm was added

Study of Efficacy and Safety of Novel Spartalizumab Combinations in Patients With Previously Treated Unresectable or Metastatic Melanoma

A Randomized, Open-label, Phase II Open Platform Study Evaluating the Efficacy and Safety of Novel Spartalizumab (PDR001) Combinations in Previously Treated Unresectable or Metastatic Melanoma

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.

ORR defined as the percentage of patients with a best overall response of either confirmed complete response (CR) or partial response (PR) as per local review by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) and assessed by computed tomography (CT)/ magnetic resonance imaging (MRI).

CR:Disappearance of all non-nodal target and non-target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

DOR defined as the time from date of first documented CR or PR to date of first documented disease progression (as per local review by RECIST v1.1 and assessed by CT/MRI) or death due to any cause. Subjects continuing without progression or death due to underlying cancer were censored at the date of their last adequate tumor assessment.

CR:Disappearance of all non-nodal target and non-target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

OS was defined as the time from date of randomization (or date of first dose of study treatment in non-randomized part) to date of death due to any cause. The OS distribution was estimated using the Kaplan-Meier method, and the medians and 95% confidence intervals of the medians were presented.

PFS was defined as the time between the date of randomization (or date of first dose of study treatment in non-randomized section) to the date of event defined as the first documented disease progression (as per local review by RECIST v1.1 and assessed by CT/MRI) or death due to any cause. If a subject had not had an event before leaving study or initiation of subsequent anticancer therapy, PFS was censored at the date of last adequate tumor assessment. The PFS distribution was estimated using the Kaplan-Meier method, medians and 95% confidence interval of the medians were presented.

DCR was defined as the percentage of participants with best overall response of CR, PR or stable disease (SD) (as per local review by RECIST v1.1 and assessed by CT/MRI).

CR:Disappearance of all non-nodal target and non-target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease.

Percentage of participants who had a PDR001 ADA positive result at baseline.

Percentage of participants who had a LAG525 ADA positive result at baseline. Only applicable for participants enrolled in Arm 1 and Arm 1A.

Percentage of participants who had an ACZ885 ADA positive result at baseline. Only applicable for subjects enrolled in Arm 3.

Percentage of participants who tested positive for treatment-induced ADA for PDR001 (subjects with ADA-negative sample at baseline with at least one post-baseline ADA positive sample) as well as treatment-boosted ADA for PDR001 (subjects with baseline positive ADA titre that was boosted to a 4-fold or higher-level following treatment).

Percentage of participants who tested positive for treatment-induced ADA for LAG525 (subjects with ADA-negative sample at baseline with at least one post-baseline ADA positive sample) as well as treatment-boosted ADA for LAG525 (subjects with baseline positive ADA titre that was boosted to a 4-fold or higher-level following treatment). Only applicable for subjects enrolled in Arm 1 and Arm 1A.

Percentage of participants who tested positive for treatment-induced ADA for ACZ885 (subjects with ADA-negative sample at baseline with at least one post-baseline ADA positive sample) as well as treatment-boosted ADA for ACZ885 (subjects with baseline positive ADA titre that was boosted to a 4-fold or higher-level following treatment). Only applicable for subjects enrolled in Arm 3.

Biomarker parameters included: 1) number of tumor infiltrating T cells (TIL), 2) activation level of TIL, and 3) changes in immune response gene expression signatures. For the number of TILs, an increase in tumoral CD8+ cell numbers compared to baseline was considered favorable. The activation level of TIL was assessed by the percentage of tumoral CD8+ cells expressing GzmB (a marker for cytotoxic activity) or Ki67 (a marker for cell proliferation), where an increase in either GZMB+/CD8+ or KI67+/CD8+ post-baseline was considered favorable. Changes in immune response gene expression signatures were evaluated by the levels in T-cell inflamed signature (TIS), where an increase from baseline was considered favorable.

To be categorized as having a pFBP, a subject must meet the favorable criteria for at least two of the three biomarker parameters. The percentage of participants with pFBP was assessed.

Any sign or symptom that occurs during the conduct of the trial and safety follow-up. Deaths in the post treatment survival follow-up are not considered AEs. The total number at risk in the post treatment survival includes patients that entered the post treatment survival follow-up period. Safety analyses were performed in the safety set, including all participants who received at least one dose of treatment

AEs collected during on-treatment period (up to 30 days post-treatment)

Arm 1: LAG525 + PDR001 (Randomized Part)- On-treatment Period

AEs collected during extended safety follow-up period (from day 31 post-treatment up to 150 days post last dose of PDR001 \[if \>30 days post-treatment\])

Arm 1: LAG525 + PDR001 (Randomized Part)- Extended Safety Follow-up

Deaths collected in the post- treatment survival follow-up period (starting from day 151 post- treatment). No AEs were collected during this period

Arm 1: LAG525 + PDR001 (Randomized Part)- Post-treatment Survival Follow-up

Arm 2: INC280+PDR001 (Randomized Part)- On-treatment Period

Arm 2: INC280+PDR001 (Randomized Part) - Extended Safety Follow-up

Arm 2: INC280+PDR001 (Randomized Part)- Post-treatment Survival Follow-up

Arm 3: ACZ885 + PDR001 (Randomized Part)- On-treatment Period

Arm 3: ACZ885 + PDR001 (Randomized Part)- Extended Safety Follow-up

Arm 3: ACZ885 + PDR001 (Randomized Part)- Post-treatment Survival Follow-up

Arm 4: LEE011 + PDR001 (Randomized Part)- On-treatment Period

Arm 4: LEE011 + PDR001 (Randomized Part)- Extended Safety Follow-up

Arm 4: LEE011 + PDR001 (Randomized Part)- Post-treatment Survival Follow-up

Arm 1A: LAG525 + PDR001 (Non-randomized Part)- On-treatment Period

Arm 1A: LAG525 + PDR001 (Non-randomized Part)- Extended Safety Follow-up

Arm 1A: LAG525 + PDR001 (Non-randomized Part)- Post-treatment Survival Follow-up

Participants randomized to receive LAG525 at a dosage of 600 mg administered intravenously every 4 weeks, in combination with PDR001 at a dosage of 400 mg administered intravenously every 4 weeks

Arm 1: LAG525 + PDR001 (Randomized Section)

Participants randomized to receive INC280 orally at a dosage of 400 mg twice daily, in combination with PDR001 at a dosage of 400 mg administered intravenously every 4 weeks

Arm 2: INC280+PDR001 (Randomized Section)

Participants randomized to receive ACZ885 at a dosage of 300 mg administered subcutaneously every 4 weeks, in combination with PDR001 at a dosage of 400 mg administered intravenously every 4 weeks

Arm 3: ACZ885 + PDR001 (Randomized Section)

Participants randomized to receive LEE011 orally at a dosage of 600 mg once daily on Days 1-21 of a 28-day cycle, in combination with PDR001 at a dosage of 400 mg administered intravenously every 4 weeks

Arm 4: LEE011 + PDR001 (Randomized Section)

Arm 1A: LAG525 + PDR001 (Non-randomized Section)

Total

Age, Categorical

Sex: Female, Male

Race (NIH/OMB)

Study director

Randomized section: All participants to whom study treatment was assigned by randomization.

Non-randomized section: All participants who received at least one dose of study treatment

Overall Response Rate (ORR)

Randomized section: All participants to whom study treatment was assigned by randomization for whom best overall response was complete response or partial response.

Non-randomized section: All participants who received at least one dose of study treatment for whom best overall response was complete response or partial response

Duration of Response (DOR)

Overall Survival (OS)

Progression Free Survival (PFS)

Disease Control Rate (DCR)

Randomized section: Participants to whom study treatment was assigned by randomization with a determinant baseline immunogenicity sample for PDR001.

Non-randomized section: Participants who received at least one dose of treatment with a determinant baseline immunogenicity sample for PDR001.

Percentage of Participants With PDR001 Anti-drug Antibodies (ADA) Positive Result at Baseline

Randomized section: Participants randomized to Arm 1 with a determinant baseline immunogenicity sample for LAG525.

Non-randomized section: Participants who received at least one dose of treatment with a determinant baseline immunogenicity sample for LAG525.

Percentage of Participants With LAG525 Anti-drug Antibodies (ADA) Positive Result at Baseline

Participants randomized to Arm 3 with a determinant baseline immunogenicity sample for ACZ885.

Percentage of Participants With ACZ885 Anti-drug Antibodies (ADA) Positive Result at Baseline

Randomized section: Participants to whom study treatment was assigned by randomization with a determinant baseline immunogenicity sample and at least one determinant post-baseline immunogenicity sample.

Non-randomized section: Participants who received at least one dose of study treatment with a determinant baseline immunogenicity sample and at least one determinant post-baseline immunogenicity sample.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Exploratory Platform Trial to Evaluate Immunotherapy Combinations With Chemotherapy for the Treatment of Patients With Previously Untreated Metastatic Pancreatic Adenocarcinoma	NCT04787991	Metastatic Panc...	Nivolumab (Coho... Ipilimumab (Coh... Hydroxychloroqu... Nab-paclitaxel ... Gemcitabine (ge... NG350A (Cohort ...	18 Years -	Cancer Insight, LLC
FUSCC Refractory TNBC Platform Study (FUTURE2.0)	NCT05749588	Triple-negative...	A1: SHR-A1811 A2: SHR-A1811 w... B1: TROP2 ADC B2: TROP2 ADC w... C1: SHR-A1811 C2: SHR-A1811 w... D1: TROP2 ADC D2: TROP2 ADC w... E1: SHR-A1811 F1: TROP2 ADC G1: SHR-A1811 H1: TROP2 ADC	18 Years -	Fudan University
Study of Efficacy and Safety of Novel Spartalizumab Combinations in Patients With Previously Treated Unresectable or Metastatic Melanoma	NCT03484923	Melanoma	PDR001 LAG525 INC280 ACZ885 LEE011	18 Years -	Novartis
Study of Efficacy and Safety of Novel Spartalizumab Combinations in Patients With Previously Treated Unresectable or Metastatic Melanoma	NCT03484923	Melanoma	PDR001 LAG525 INC280 ACZ885 LEE011	18 Years -	Novartis
Optimal Precision TherapIes to CustoMISE Care in Childhood and Adolescent Cancer	NCT06208657	Childhood Cance... Childhood Solid... Childhood Brain... Recurrent Cance... Refractory Canc...	Paxalisib, Irin... Pimasertib	0 Years - 21 Years	Australian & New Zealand Children's Haematology/Oncology Group
Phase 2 Platform Study in Patients With Advanced Non-Small Lung Cancer Who Progressed on First-Line Osimertinib Therapy (ORCHARD)	NCT03944772	Non-Small Cell ...	Osimertinib Savolitinib Gefitinib Necitumumab Durvalumab Carboplatin Pemetrexed Alectinib Selpercatinib Selumetinib Etoposide Cisplatin Datopotamab der...	18 Years - 130 Years	AstraZeneca
Platform Study for the Treatment of Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma (PRISM Study)	NCT03527147	NHL DLBCL Non-hodgkin's L... Diffuse Large B...	AZD9150 Acalabrutinib AZD6738 Hu5F9-G4 Rituximab AZD5153	18 Years - 130 Years	Acerta Pharma BV

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