- |||||||||| Unbiased Drug Discovery Approaches to Identify Novel Radiosensitizers from Cancer Therapy Evaluation Program (CTEP) Portfolio of Drugs in Pancreatic Cancer (Room W176) - Sep 24, 2019 - Abstract #ASTRO2019ASTRO_3533;
The cell dispensing was automated to ensure uniform seeding of cell number and the drugs were added at six different concentrations ranging from 0.1nM to 10uM at three incubation time points (1h, 2h, 4h) before or after 2 Gy exposure with or without capecitabine (10 uM)...Selumetinib, dabrafenib, and veliparib showed radiosensitization in HPAC cells; alisertib, dasatinib, AZD8186, copanlisib, and VX-970 showed radiosensitization in Panc1 cells; and AMG 232, temsirolimus, and olaparib showed radiosensitization in both Panc1 and HPAC cells... High-throughput clonogenic assays coupled with validation by classical clonogenic assays may provide an unbiased in vitro approach to compare putative radiosensitizers head-to-head and allow rational advancement of select agents for additional evaluation for repurposing as radiosensitizers.
- |||||||||| KRT-232 / Amgen, Kartos Therapeutics, selumetinib (AZD6244) / Merck (MSD), AstraZeneca
The combination of MEK and MDM2 inhibitors demonstrates promising antitumor efficacy in MAPK altered patient-derived thyroid and colorectal cancer models (Board 80: Level 2 - Hall D) - Sep 18, 2019 - Abstract #AACRNCIEORTC2019AACR_NCI_EORTC_512; Treatment/Control ratio % ((median tumor volume of treatment group / control group) x 100) was obtained from each combination arm across in vivo experiments (31 % (range 12%-62%)) and it was greater than monotherapy alone (Selumetinib 51%; range 21%-76%, AMG232 77%; range 38%-100%). Conclusion Our preclinical findings demonstrate enhanced anti-tumor efficacy when combining Selumetinib with AMG232, which supports further evaluation of MEK/MDM2 inhibition in patients with MAPK altered colorectal and thyroid cancer with wild-type TP53 status.
- |||||||||| KRT-232 / Amgen, Kartos Therapeutics
MDM2 inhibitor KRT-232 extends survival in glioblastoma patient-derived xenograft models (Board 51: Level 2 - Hall D) - Sep 18, 2019 - Abstract #AACRNCIEORTC2019AACR_NCI_EORTC_483; Despite low BBB penetration as determined by pharmacokinetic studies, KRT-232 alone and in combination with RT is an effective treatment in a pre-clinical model of glioblastoma. Future studies will evaluate KRT-232 pharmacodynamic responses as well as PDX orthotopic combination therapy in additional MDM2 amplified and non-amplified/p53 wildtype lines to understand if this therapy can be used in a larger population of GBM tumors.
- |||||||||| M7583 / EMD Serono, Telios Pharma
Trial primary completion date, Combination therapy, Monotherapy: MS200662_0001: Phase I/II, FIH, Dose Escalation Trial of TL-895 and Expansion of TL-895 Monotherapy and Combination Therapy With Navtemadlin in Tx-Na (clinicaltrials.gov) - May 3, 2019 P1/2, N=18, Active, not recruiting, N=80 --> 46 Trial primary completion date: May 2018 --> May 2019
- |||||||||| navtemadlin (KRT-232) / Kartos Therap
Trial completion, Trial completion date, Trial primary completion date, Metastases: A Phase 1b/2a Study Evaluating AMG 232 in Metastatic Melanoma (clinicaltrials.gov) - Dec 17, 2018 P1b/2a, N=31, Completed, Initiation date: Oct 2018 --> Jan 2019 Active, not recruiting --> Completed | Trial completion date: Oct 2019 --> Dec 2018 | Trial primary completion date: Oct 2019 --> Dec 2018
- |||||||||| M7583 / EMD Serono, Telios Pharma
Trial primary completion date, Combination therapy, Monotherapy: MS200662_0001: Phase I/II, FIH, Dose Escalation Trial of TL-895 and Expansion of TL-895 Monotherapy and Combination Therapy With Navtemadlin in Tx-Na (clinicaltrials.gov) - Oct 18, 2018 P1/2, N=18, Active, not recruiting, Suspended --> Recruiting Trial primary completion date: Aug 2018 --> May 2018
- |||||||||| navtemadlin (KRT-232) / Kartos Therap
Trial completion date, Metastases: A Phase 1b/2a Study Evaluating AMG 232 in Metastatic Melanoma (clinicaltrials.gov) - Oct 12, 2018 P1b/2a, N=31, Active, not recruiting, Trial primary completion date: Aug 2018 --> May 2018 Trial completion date: Aug 2021 --> Oct 2019
- |||||||||| KRT-232 / Amgen, Kartos Therap
Journal: Radiosensitization of adenoid cystic carcinoma with MDM2 inhibition. (Pubmed Central) - May 26, 2018 Post treatment analysis revealed that while both AMG 232 and RT alone induced TP53 tumor suppressive activities, combination therapy amplified this response with potent induction of apoptosis after combination treatment. These data identify that MDM2 inhibition can provide potent radiosensitization in TP53-WT ACC. In light of the absence of effective systemic agents for ACC, the powerful response profile observed here suggests that clinical trial evaluation of this drug/RT combination may be warranted to improve local control in this challenging malignancy.
- |||||||||| navtemadlin (KRT-232) / Kartos Therap
Enrollment open, Combination therapy: Testing the Addition of KRT-232 (AMG 232) to Usual Chemotherapy for Relapsed Multiple Myeloma (clinicaltrials.gov) - Apr 24, 2018 P1, N=40, Recruiting, These data identify that MDM2 inhibition can provide potent radiosensitization in TP53-WT ACC. In light of the absence of effective systemic agents for ACC, the powerful response profile observed here suggests that clinical trial evaluation of this drug/RT combination may be warranted to improve local control in this challenging malignancy. Suspended --> Recruiting
- |||||||||| navtemadlin (KRT-232) / Kartos Therap
Enrollment closed, Enrollment change, Trial primary completion date, Metastases: A Phase 1b/2a Study Evaluating AMG 232 in Metastatic Melanoma (clinicaltrials.gov) - Feb 19, 2018 P1b/2a, N=31, Active, not recruiting, Not yet recruiting --> Recruiting | Initiation date: Jan 2018 --> Feb 2018 Recruiting --> Active, not recruiting | N=138 --> 31 | Trial primary completion date: Apr 2018 --> Oct 2019
- |||||||||| M7583 / EMD Serono, Telios Pharma
Enrollment closed, Enrollment change, Trial completion date, Trial primary completion date, Combination therapy, Monotherapy: MS200662_0001: Phase I/II, FIH, Dose Escalation Trial of TL-895 and Expansion of TL-895 Monotherapy and Combination Therapy With Navtemadlin in Tx-Na (clinicaltrials.gov) - Feb 19, 2018 P1/2, N=20, Active, not recruiting, Recruiting --> Active, not recruiting | N=138 --> 31 | Trial primary completion date: Apr 2018 --> Oct 2019 Recruiting --> Active, not recruiting | N=60 --> 20 | Trial primary completion date: Oct 2019 --> Nov 2018 | Trial completion date: Dec 2019 --> Oct 2019
- |||||||||| navtemadlin (KRT-232) / Kartos Therap
Enrollment open, Trial primary completion date, Combination therapy: Testing the Addition of KRT-232 (AMG 232) to Usual Chemotherapy for Relapsed Multiple Myeloma (clinicaltrials.gov) - Nov 6, 2017 P1, N=40, Recruiting, Not yet recruiting --> Recruiting Not yet recruiting --> Recruiting | Trial primary completion date: Jul 2018 --> Mar 2019 | Not yet recruiting --> Recruiting | Trial primary completion date: Jul 2018 --> Mar 2019
- |||||||||| M7583 / EMD Serono, Telios Pharma
Enrollment change, Combination therapy, Monotherapy: MS200662_0001: Phase I/II, FIH, Dose Escalation Trial of TL-895 and Expansion of TL-895 Monotherapy and Combination Therapy With Navtemadlin in Tx-Na (clinicaltrials.gov) - Aug 14, 2017 P1/2, N=60, Recruiting, Active, not recruiting --> Completed N=20 --> 60
- |||||||||| M7583 / EMD Serono, Telios Pharma
Enrollment change, Trial primary completion date, Combination therapy, Monotherapy: MS200662_0001: Phase I/II, FIH, Dose Escalation Trial of TL-895 and Expansion of TL-895 Monotherapy and Combination Therapy With Navtemadlin in Tx-Na (clinicaltrials.gov) - Jul 6, 2017 P1/2, N=20, Recruiting, Trial primary completion date: Dec 2017 --> Apr 2018 N=60 --> 20 | Trial primary completion date: Jun 2019 --> Oct 2019
- |||||||||| M7583 / EMD Serono, Telios Pharma
Enrollment open, Combination therapy, Monotherapy: MS200662_0001: Phase I/II, FIH, Dose Escalation Trial of TL-895 and Expansion of TL-895 Monotherapy and Combination Therapy With Navtemadlin in Tx-Na (clinicaltrials.gov) - Oct 18, 2016 P1/2, N=60, Recruiting, Recruiting --> Active, not recruiting | N=130 --> 36 Not yet recruiting --> Recruiting
- |||||||||| navtemadlin (KRT-232) / Kartos Therap
Enrollment closed, Enrollment change, Trial primary completion date, Metastases: A Phase 1 Study Evaluating AMG 232 in Advanced Solid Tumors or Multiple Myeloma (clinicaltrials.gov) - Sep 28, 2016 P1, N=107, Active, not recruiting, Trial primary completion date: Jun 2018 --> Dec 2017 Recruiting --> Active, not recruiting | N=155 --> 107 | Trial primary completion date: Aug 2016 --> Mar 2017
- |||||||||| navtemadlin (KRT-232) / Kartos Therap
Phase classification, Metastases: A Phase 1b/2a Study Evaluating AMG 232 in Metastatic Melanoma (clinicaltrials.gov) - Aug 19, 2016 P1b/2a, N=138, Recruiting, Recruiting --> Active, not recruiting | N=155 --> 107 | Trial primary completion date: Aug 2016 --> Mar 2017 Phase classification: P1/2 --> P1b/2a
|