SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT02404441

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

Open Label Multicenter Phase I/II Study of the Safety and Efficacy of PDR001 Administered to Patients With Advanced Malignancies

The purpose of this "first-in-human" study of PDR001 is to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and antitumor activity of PDR001 administered i.v. as a single agent to adult patients with solid tumors. By blocking the interaction between PD-1 and its ligands, PD-L1 and PD-L2, PDR001 inhibits the PD-1 immune checkpoint, resulting in activation of an antitumor immune response by activating effector T-cells and inhibiting regulatory T-cells. This study has been designed as a phase I/II, multi-center, open-label study starting with a phase I dose escalation part followed by a phase II part. PDR001 will be administered every 2 weeks until patient experiences unacceptable toxicity, progressive disease per immune related Response Criteria (irRC) and/or treatment is discontinued at the discretion of the investigator or the patient.

NCT02404441 Melanoma NSCLC Triple Negative Breast Cancer Anaplastic Thyroid Cancer Other Solid Tumors
MeSH: Thyroid Neoplasms Triple Negative Breast Neoplasms Thyroid Carcinoma, Anaplastic
HPO: Anaplastic thyroid carcinoma Neoplasm of the thyroid gland Thyroid adenoma Thyroid carcinoma Thyroid follicular adenoma

1 Interventions

Name: PDR001

Description: anti-PD1 antibody

Type: Biological

patients with solid tumors Selected tumor types


Primary Outcomes

Description: To estimate the recommended phase 2 dose (RP2D) and/or the maximum tolerated dose (MTD) for PDR001

Measure: Part l: The exposure (AUC(0-336h)) after first dose of treatment

Time: First 28 days of treatment

Description: To estimate the RP2D and/or the MTD for PDR001

Measure: Part l: Incidence of dose limiting toxicities (DLTs)

Time: First 28 days of treatment

Description: As per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 - to estimte the anti-tumor activity of PDR001. Each cycle = 28 days

Measure: Part ll: Overall response Rate (ORR)

Time: when all patients have completed at least 6 cycles of treatment or discontinued treatment. An average of 1 year duration is expected.

Secondary Outcomes

Description: Safety as assessed by Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), including changes in laboratory parameters, vital signs and electrocardiograms (ECGs) Tolerability as assessed by dose interruptions, reductions and dose intensity

Measure: Safety and Tolerability as assessed by incidence and severity of adverse events, dose interruptions, reductions and dose intensity

Time: continuously during study until 30 days after post study treatment

Description: To assess emergence of anti-PDR001 antibodies following one or more intravenous (i.v.) infusions of PDR001. Each cycle = 28 days; End of treatment = expected to be in average 1 year after the start of study treatment

Measure: Presence and/or concentration of anti-PDR001

Time: Cycle 1 day 1; Cycle 2 day 1; Cycle 3 day 1; Cycle 4 day 1; Cycle 5 day 1; Cycle 6 day 1; End of Treatment.

Description: Preliminary antitumor activity of PDR001

Measure: Overall Response Rate (ORR) - Phase l only

Time: every 8 weeks until cycle 11 and then every 12 weeks from the start of study until end of disease progression follow-up. An average of 1 year duration is expected.

Description: Preliminary antitumor activity of PDR001

Measure: Progression Free Survival (PFS) - Phase l/ll

Time: every 8 weeks until cycle 11 and then every 12 weeks from the start of study until end of disease progression follow-up. An average of 1 year duration is expected.

Description: Preliminary antitumor activity of PDR001

Measure: Duration of Response (DOR) - Phase l/ll

Time: every 8 weeks until cycle 11 and then every 12 weeks from the start of study until end of disease progression follow-up. An average of 1 year duration is expected.

Description: Preliminary antitumor activity of PDR001

Measure: Disease Control Rate (DCR) - Phase l/ll

Time: every 8 weeks until cycle 11 and then every 12 weeks from the start of study until end of disease progression follow-up. An average of 1 year duration is expected.

Description: Preliminary antitumor activity of PDR001

Measure: Overall Response Rate (ORR) per immune related Response Criteria - Phase ll only

Time: every 8 weeks until cycle 11 and then every 12 weeks from the start of study until end of disease progression follow-up. An average of 1 year duration is expected.

Description: e.g., AUC, Cmax, Tmax, half-life to characterize the pharmacokinetic profile of PDR001. End of treatment = expected to be in average 1 year after the start of study treatment

Measure: Composite Serum pharmacokinetics (PK) parameters

Time: cycles 1 days 1, 2, 3, 4, 8, 11, 15. Cycle 2 day 1. Cycle 3 days 1, 2, 3, 4, 8, 11, 15. Cycle 4 day 1, Cycle 5 day 1, Cycle 6 day 1, End of Treatment.

Description: To characterize the pharmacokinetic profile of PDR001. End of treatment = expected to be in average 1 year after the start of study treatment

Measure: Serum concentration vs. time profiles

Time: cycles 1 days 1, 2, 3, 4, 8, 11, 15. Cycle 2 day 1. Cycle 3 days 1, 2, 3, 4, 8, 11, 15. Cycle 4 day 1, Cycle 5 day 1, Cycle 6 day 1, End of Treatment.

Purpose: Treatment

Allocation: Non-Randomized

Single Group Assignment


There is one SNP

SNPs


1 L858R

Only patients with EGFR mutation-negative tumor are eligible (defined as negative for exon 19 deletions and for the L858R mutation in EGFR at a minimum; however, if more extensive EGFR mutation testing has been performed, the tumor must not harbor any known activating EGFR mutations in Exons 18-21 in order to be considered EGFR mutation-negative). --- L858R ---



HPO Nodes


HPO:
Anaplastic thyroid carcinoma
Neoplasm of the thyroid gland
Genes 61
FOXE1 CDKN1A PMS1 CDKN1B KRAS CDKN2B CDKN2C TGFBR2 MSH6 RASGRP1 SEMA3D SEMA3C BMPR1A PMS2 KLLN MLH3 NRAS LMNA NRTN PIK3CA NTRK1 SLC26A4 JAG1 KCNJ10 WRN HRAS APC MLH1 PRKAR1A FLCN CASP10 PRKCD AKT1 RPS20 HABP2 MSH2 MSH3 CDC73 KEAP1 GREM1 MINPP1 GNAS SEMA4A RET PTEN ECE1 FAS FASLG EPCAM GDNF DICER1 SEC23B EDN3 EDNRB SDHB SDHC SDHD FOXI1 MEN1 FAN1 TG
Thyroid adenoma
Genes 16
PTEN CDKN1A FAS CDKN1B FASLG PRKAR1A CDKN2B CDKN2C PIK3CA CASP10 PRKCD RASGRP1 AKT1 MSH3 CDC73 MEN1
Thyroid carcinoma
Genes 34
FOXE1 HRAS APC PRKAR1A FLCN CASP10 PRKCD RASGRP1 AKT1 BMPR1A HABP2 KLLN CDC73 KEAP1 GREM1 MINPP1 RET NRAS PTEN FAS FASLG PIK3CA DICER1 NTRK1 SEC23B SLC26A4 JAG1 KCNJ10 SDHB SDHC SDHD FOXI1 TG WRN
Thyroid follicular adenoma