SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT02346955

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

A Phase 1, Open-Label, Multicenter, Multi-Dose Escalation Study of CM-24 (MK-6018) as Monotherapy and In Combination With Pembrolizumab (MK-3475) in Subjects With Selected Advanced or Recurrent Malignancies

The purpose of this study is to evaluate the safety and tolerability of humanized IgG4 (kappa) isotype monoclonal antibody against CEACAM1 (CM-24 [MK-6018]), administered intravenously as monotherapy and in combination with Pembrolizumab (MK-3475), in participants with selected advanced or recurrent malignancies. Escalating multiple doses will be evaluated to determine the recommended dose for Phase 2 clinical studies.

NCT02346955 Non-small Cell Lung Carcinoma (NSCLC) Melanoma Bladder Cancer Colorectal Cancer Gastric Cancer Ovarian Cancer
MeSH: Colorectal Neoplasms Urinary Bladder Neoplasms Lung Neoplasms Carcinoma, Non-Small-Cell Lung
HPO: Bladder neoplasm Neoplasm of the large intestine Neoplasm of the lung Non-small cell lung carcinoma

2 Interventions

Name: CM-24 (MK-6018)

Description: humanized IgG4 (kappa) isotype monoclonal antibody against CEACAM1 by intravenous (IV) infusion

Type: Biological

Cohort A Monotherapy Dose Escalation Cohort B Combination Dose Escalation Cohort C Monotherapy Expansion Cohort D Monotherapy Expansion Cohort E Monotherapy Expansion Cohort C1 Combination Expansion Cohort D1 Combination Expansion Cohort E1 Combination Expansion Cohort F Combination Expansion

Name: Pembrolizumab (MK-3475)

Description: 200 mg of Pembrolizumab by IV infusion

Type: Biological

Cohort B Combination Dose Escalation Cohort C1 Combination Expansion Cohort D1 Combination Expansion Cohort E1 Combination Expansion Cohort F Combination Expansion


Primary Outcomes

Measure: Number of participants with Adverse Events (AEs)

Time: From time of first dose until the end of follow-up (up to 123 weeks)

Measure: Number of participants discontinuing study drug due to AEs

Time: From time of first dose until the end of follow-up (up to 105 weeks)

Measure: Number of participants with a Dose Limiting Toxicity (DLT)

Time: From time of first dose until the end of follow-up (up to 12 weeks)

Secondary Outcomes

Measure: Maximum drug concentration in serum/plasma (Cmax)

Time: For Cycles 1-35: all infusions at pre-infusion. For Cycle 1 first & fourth infusion: at end of infusion; 1, 4, 8 hours post-infusion; and Days 2, 3, 5, 8 post-infusion. For Cycle 1 fourth infusion also at Days 15, 22, 36 post-infusion.

Measure: Time to reach Cmax in serum/plasma (Tmax)

Time: For Cycles 1-35: all infusions at pre-infusion. For Cycle 1 first & fourth infusion: at end of infusion; 1, 4, 8 hours post-infusion; and Days 2, 3, 5, 8 post-infusion. For Cycle 1 fourth infusion also at Days 15, 22, 36 post-infusion.

Measure: Terminal-phase elimination half-life in serum/plasma (t1/2)

Time: For Cycles 1-35: all infusions at pre-infusion. For Cycle 1 first & fourth infusion: at end of infusion; 1, 4, 8 hours post-infusion; and Days 2, 3, 5, 8 post-infusion. For Cycle 1 fourth infusion also at Days 15, 22, 36 post-infusion.

Measure: Area under the plasma/serum concentration versus time curve from time zero to the last measured time (AUC 0-T)

Time: For Cycles 1-35: all infusions at pre-infusion. For Cycle 1 first & fourth infusion: at end of infusion; 1, 4, 8 hours post-infusion; and Days 2, 3, 5, 8 post-infusion. For Cycle 1 fourth infusion also at Days 15, 22, 36 post-infusion.

Measure: Area under the plasma/serum concentration versus time curve from time zero to infinity (AUC 0-∞)

Time: For Cycles 1-35: all infusions at pre-infusion. For Cycle 1 first & fourth infusion: at end of infusion; 1, 4, 8 hours post-infusion; and Days 2, 3, 5, 8 post-infusion. For Cycle 1 fourth infusion also at Days 15, 22, 36 post-infusion.

Measure: Objective Response Rate (ORR) defined using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria

Time: From time of screening until the end of follow-up (up to 123 weeks)

Measure: Time from ORR to disease progression or death (DOR)

Time: From time of screening until the end of follow-up (up to 123 weeks)

Purpose: Treatment

Allocation: Non-Randomized

Single Group Assignment


There are 2 SNPs

SNPs


1 V600E

- Participants in the Monotherapy Expansion Cohort must have one of the following advanced or recurrent malignancies: cutaneous melanoma showing primary progression following treatment with an anti-programmed cell death (PD) or anti-PDL1 regimen; or anti-PD1 or anti-PD-L1 treatment-naïve colorectal or gastric cancer, including gastroesophageal junction cancer of Siewert Type II and Type III. - Participants in the Combination Expansion Cohorts must have one of the following advanced or recurrent malignancies: non-small cell lung adenocarcinoma or cutaneous melanoma showing primary progression following treatment with an anti-PD1 or anti-PD-L1 regimen; or anti-PD1 or anti-PD-L1 treatment-naïve colorectal or gastric cancer, including gastroesophageal junction cancer of Siewert Type II and Type III. - Melanoma with BRAF V600E or V600K mutation-positive melanoma must have progressed on, or were intolerant to, prior BRAF- or MEK-inhibitor therapy - Must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 with progressing or new tumors since last antitumor therapy - Must have adequate hematologic, renal, and liver function - Eastern Cooperative Oncology Group (ECOG) performance status 0-1 - Females must not be pregnant (negative human chorionic gonadotropin test within 72 hours prior to receiving the first dose of study medication) or breastfeeding - Women of childbearing potential and male participants must agree to use adequate contraception throughout the study and for up to 180 days after study treatment - An estimated life expectancy of at least 3 months - Must consent to provide an archival tumor biopsy sample at any time point from screening to study exit - Must consent to allow the acquisition of new tissue biopsy samples during the study Exclusion Criteria: - History of severe hypersensitivity reactions or immune related adverse events to other monoclonal antibodies - History of other active malignancy within the prior 2 years - History of insulin-dependent or uncontrolled Diabetes Mellitus - History of inflammatory bowel disease - Autoimmune disorders - Known HIV and/or Hepatitis B or C infections - Known systemic bleeding or platelet disorder - Receipt of live vaccines with 4 weeks (28 days) of study - History or evidence of non-infectious pneumonitis that required steroids or current pneumonitis Inclusion Criteria: - Males and females ≥18 years of age - Participants in the Dose Escalation portion must have one of the following advanced or recurrent malignancies: gastrointestinal (colorectal or gastric); ovarian; melanoma; non-small cell lung adenocarcinoma; or bladder. --- V600E ---

- Participants in the Monotherapy Expansion Cohort must have one of the following advanced or recurrent malignancies: cutaneous melanoma showing primary progression following treatment with an anti-programmed cell death (PD) or anti-PDL1 regimen; or anti-PD1 or anti-PD-L1 treatment-naïve colorectal or gastric cancer, including gastroesophageal junction cancer of Siewert Type II and Type III. - Participants in the Combination Expansion Cohorts must have one of the following advanced or recurrent malignancies: non-small cell lung adenocarcinoma or cutaneous melanoma showing primary progression following treatment with an anti-PD1 or anti-PD-L1 regimen; or anti-PD1 or anti-PD-L1 treatment-naïve colorectal or gastric cancer, including gastroesophageal junction cancer of Siewert Type II and Type III. - Melanoma with BRAF V600E or V600K mutation-positive melanoma must have progressed on, or were intolerant to, prior BRAF- or MEK-inhibitor therapy - Must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 with progressing or new tumors since last antitumor therapy - Must have adequate hematologic, renal, and liver function - Eastern Cooperative Oncology Group (ECOG) performance status 0-1 - Females must not be pregnant (negative human chorionic gonadotropin test within 72 hours prior to receiving the first dose of study medication) or breastfeeding - Women of childbearing potential and male participants must agree to use adequate contraception throughout the study and for up to 180 days after study treatment - An estimated life expectancy of at least 3 months - Must consent to provide an archival tumor biopsy sample at any time point from screening to study exit - Must consent to allow the acquisition of new tissue biopsy samples during the study Exclusion Criteria: - History of severe hypersensitivity reactions or immune related adverse events to other monoclonal antibodies - History of other active malignancy within the prior 2 years - History of insulin-dependent or uncontrolled Diabetes Mellitus - History of inflammatory bowel disease - Autoimmune disorders - Known HIV and/or Hepatitis B or C infections - Known systemic bleeding or platelet disorder - Receipt of live vaccines with 4 weeks (28 days) of study - History or evidence of non-infectious pneumonitis that required steroids or current pneumonitis Non-small Cell Lung Carcinoma (NSCLC) Melanoma Bladder Cancer Colorectal Cancer Gastric Cancer Ovarian Cancer Colorectal Neoplasms Urinary Bladder Neoplasms Lung Neoplasms Carcinoma, Non-Small-Cell Lung null --- V600E ---


2 V600K

- Participants in the Monotherapy Expansion Cohort must have one of the following advanced or recurrent malignancies: cutaneous melanoma showing primary progression following treatment with an anti-programmed cell death (PD) or anti-PDL1 regimen; or anti-PD1 or anti-PD-L1 treatment-naïve colorectal or gastric cancer, including gastroesophageal junction cancer of Siewert Type II and Type III. - Participants in the Combination Expansion Cohorts must have one of the following advanced or recurrent malignancies: non-small cell lung adenocarcinoma or cutaneous melanoma showing primary progression following treatment with an anti-PD1 or anti-PD-L1 regimen; or anti-PD1 or anti-PD-L1 treatment-naïve colorectal or gastric cancer, including gastroesophageal junction cancer of Siewert Type II and Type III. - Melanoma with BRAF V600E or V600K mutation-positive melanoma must have progressed on, or were intolerant to, prior BRAF- or MEK-inhibitor therapy - Must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 with progressing or new tumors since last antitumor therapy - Must have adequate hematologic, renal, and liver function - Eastern Cooperative Oncology Group (ECOG) performance status 0-1 - Females must not be pregnant (negative human chorionic gonadotropin test within 72 hours prior to receiving the first dose of study medication) or breastfeeding - Women of childbearing potential and male participants must agree to use adequate contraception throughout the study and for up to 180 days after study treatment - An estimated life expectancy of at least 3 months - Must consent to provide an archival tumor biopsy sample at any time point from screening to study exit - Must consent to allow the acquisition of new tissue biopsy samples during the study Exclusion Criteria: - History of severe hypersensitivity reactions or immune related adverse events to other monoclonal antibodies - History of other active malignancy within the prior 2 years - History of insulin-dependent or uncontrolled Diabetes Mellitus - History of inflammatory bowel disease - Autoimmune disorders - Known HIV and/or Hepatitis B or C infections - Known systemic bleeding or platelet disorder - Receipt of live vaccines with 4 weeks (28 days) of study - History or evidence of non-infectious pneumonitis that required steroids or current pneumonitis Inclusion Criteria: - Males and females ≥18 years of age - Participants in the Dose Escalation portion must have one of the following advanced or recurrent malignancies: gastrointestinal (colorectal or gastric); ovarian; melanoma; non-small cell lung adenocarcinoma; or bladder. --- V600E --- --- V600K ---

- Participants in the Monotherapy Expansion Cohort must have one of the following advanced or recurrent malignancies: cutaneous melanoma showing primary progression following treatment with an anti-programmed cell death (PD) or anti-PDL1 regimen; or anti-PD1 or anti-PD-L1 treatment-naïve colorectal or gastric cancer, including gastroesophageal junction cancer of Siewert Type II and Type III. - Participants in the Combination Expansion Cohorts must have one of the following advanced or recurrent malignancies: non-small cell lung adenocarcinoma or cutaneous melanoma showing primary progression following treatment with an anti-PD1 or anti-PD-L1 regimen; or anti-PD1 or anti-PD-L1 treatment-naïve colorectal or gastric cancer, including gastroesophageal junction cancer of Siewert Type II and Type III. - Melanoma with BRAF V600E or V600K mutation-positive melanoma must have progressed on, or were intolerant to, prior BRAF- or MEK-inhibitor therapy - Must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 with progressing or new tumors since last antitumor therapy - Must have adequate hematologic, renal, and liver function - Eastern Cooperative Oncology Group (ECOG) performance status 0-1 - Females must not be pregnant (negative human chorionic gonadotropin test within 72 hours prior to receiving the first dose of study medication) or breastfeeding - Women of childbearing potential and male participants must agree to use adequate contraception throughout the study and for up to 180 days after study treatment - An estimated life expectancy of at least 3 months - Must consent to provide an archival tumor biopsy sample at any time point from screening to study exit - Must consent to allow the acquisition of new tissue biopsy samples during the study Exclusion Criteria: - History of severe hypersensitivity reactions or immune related adverse events to other monoclonal antibodies - History of other active malignancy within the prior 2 years - History of insulin-dependent or uncontrolled Diabetes Mellitus - History of inflammatory bowel disease - Autoimmune disorders - Known HIV and/or Hepatitis B or C infections - Known systemic bleeding or platelet disorder - Receipt of live vaccines with 4 weeks (28 days) of study - History or evidence of non-infectious pneumonitis that required steroids or current pneumonitis Non-small Cell Lung Carcinoma (NSCLC) Melanoma Bladder Cancer Colorectal Cancer Gastric Cancer Ovarian Cancer Colorectal Neoplasms Urinary Bladder Neoplasms Lung Neoplasms Carcinoma, Non-Small-Cell Lung null --- V600E --- --- V600K ---



HPO Nodes


HPO:
Bladder neoplasm
Genes 22
PTEN HRAS APC KRAS RB1 AAGAB FLCN PIK3CA COL14A1 RNF43 AKT1 EP300 NTHL1 FGFR3 AXIN2 ATP7A SRC CTNNB1 DLC1 BUB1B NRAS DCC
Neoplasm of the large intestine
Genes 71
FOXE1 PMS1 CDKN2A KRAS MST1 TGFBR2 STK11 MSH6 TCF4 BMPR1A PMS2 KLLN MLH3 DLC1 NRAS BRCA1 BRCA2 PDGFRA DOCK8 PIK3CA GPR35 POLD1 NTHL1 POLE SRC BUB1 SH3KBP1 BUB1B CHEK2 APC MLH1 PRKAR1A FLCN COL14A1 AKT1 RPS19 RPS20 HABP2 MSH2 FGFR3 MSH3 KEAP1 GREM1 MINPP1 SEMA4A CTNNB1 DCC BUB3 PTEN MDM2 CEP57 ENG AAGAB TRIP13 KIT EPCAM DICER1 RNF43 PALLD EP300 PALB2 SEC23B MUTYH SDHA TP53 SDHB SDHC SDHD AXIN2 SMAD4 FAN1
Neoplasm of the lung
Genes 43
WT1 KRAS SLC22A18 STK11 IRF1 AKT1 C11ORF95 PRKN PPP2R1B ERBB2 TRPV3 TSC1 POU6F2 TSC2 EWSR1 RELA KEAP1 REST DIS3L2 SFTPA2 GPC3 MBTPS2 LMNA PTEN BRAF BRCA2 EGFR RB1 TRIP13 PDGFRB TERT SFTPC PIK3CA TRIM28 DICER1 MAP3K8 HPGD SLCO2A1 H19 TP53 NOTCH3 BAP1 WRN
Non-small cell lung carcinoma
Genes 2
TP53 BAP1