The safety and efficacy of the combination of vidutolimod (CMP-001) and nivolumab (Opdivo) is currently under investigation in patients with PD-1–refractory advanced melanoma, as part of the ongoing phase 2 CMP-001-010 trial (NCT04698187).

In May 2021, patient dosing with the combination was initiated for the trial. Previously, dosing with vidutolimod/nivolumab was also initiated in another phase 2/3 trial (NCT04695977)

 that is examining the safety and efficacy of the frontline regimen compared with single-agent nivolumab in patients with metastatic or unresectable melanoma. Findings from both of the trials are expected to support a biologics license application for the doublet as a potential option for patients with PD-1–refractory advanced disease.

"Initiation of dosing in this pivotal trial is an important milestone as we move toward potential registration of vidutolimod in melanoma," Barry Labinger, president and chief executive officer of Checkmate Pharmaceuticals, stated in a press release. "Melanoma is estimated to be the fifth most diagnosed cancer in the United States, with more than 100,000 new cases and 7,000 deaths per year. There is a significant unmet medical need for patients who have progressed following treatment with anti–PD-1 therapy since there is no well-established standard of care."

Vidutolimod, an advanced generation toll-like receptor 9 agonist, is delivered as a biologic virus-like particle and utilizes CpG-A oligodeoxynucleotide as a key component. The mechanism of action of the agent provides it with the potential to produce tumor-targeted T cells that are able to eliminate a tumor locally and systemically when paired with checkpoint inhibitors.

 This combination has been hypothesized to improve outcomes for patients whose tumors are not responsive to immunotherapy agents.

The multicenter, open-label study plans to enroll an estimated 100 patients. To be eligible for enrollment, patients needed to be at least 18 years of age and have histopathologically-confirmed diagnosis of malignant melanoma that is metastatic or unresectable at the time of screening.

 Patients also needed to be refractory to PD-1 blockade either as monotherapy or in combination with other options. Additionally, patients had to have measurable disease, an ECOG performance status of 0 or 1, and acceptable organ function.

Those who have been diagnosed with uveal, acral, or mucosal melanoma; who have received radiation therapy; or have been treated with complementary therapy 2 weeks prior to the first study dose were not able to enroll to the trial. Additional exclusion criteria include those who require corticosteroids equal to 10 mg of prednisone per day, have a history of grade 4 immune-related adverse effects (AE) from an anti–PD-1 antibody, those who have not fully recovered from previous AEs, or those who have a history of, or active, pneumonitis or interstitial lung disease.

Patients enrolled to the trial will receive 10 mg of intravenous vidutolimod weekly for 7 doses followed by administration every 3 weeks. Additionally, patients will be given 360 mg of nivolumab intravenously every 3 weeks.

The primary outcome measure for the study is objective response rate (ORR). Key secondary outcomes include safety and tolerability, duration of response (DOR), treatment response in non-injected target lesions, progression-free survival, and overall survival, among others.

Vidutolimod was previously examined in combination with pembrolizumab

 (Keytruda) and was found to overcome PD-1 blockade resistance in patients with advanced melanoma.

 The results of the phase 1 CMP-001-001 trial (NCT02680184), which were presented during the 

, demonstrated that the combination elicited a best ORR per RECIST v1.1 criteria of 23.5% (95% CI, 15.5%-33.1%) Moreover, post-progression responders achieved a best ORR of 27.6% (95% CI, 19.0%-37.6%). Those who had previously progressed on PD-1 blockade experienced a DOR of 19.9 months.

Vidutolimod is alo under examination in combination with pembrolizumab in patients with recurrent or metastatic head and neck squamous cell carcinoma as part of a phase 2 study (NCT04633278).

 The trial will specifically be focused on patients who have not previously received a PD-1–blocking antibody.

Checkmate Pharmaceuticals announces initiation of patient dosing in potential registration trial of vidutolimod (CMP-001) in patients with anti-PD-1 refractory advanced melanoma. News release. Checkmate Pharmaceuticals, Inc. May 4, 2021. Accessed May 20, 2021. 

CMP-001 in combination with nivolumab compared to nivolumab monotherapy in subjects with advanced melanoma. ClinicalTrials.gov. Updated March 18, 2021. Accessed May 20, 2021. 

https://www.clinicaltrials.gov/ct2/show/NCT04695977

Mechanism of action: dedicated to harnessing the power of the immune system to combat cancer. Checkmate Pharmaceuticals. Accessed May 20, 2021. 

CMP-001 in combination with nivolumab in subjects with advanced melanoma. ClinicalTrials.gov. Updated May 14, 2021. Accessed May 20, 2021. 

https://clinicaltrials.gov/ct2/show/NCT04698187

M, Zakharia Y, Davar D, et al. Intratumoral injection of CMP-001, a toll-like (TLR9) receptor agonist, in combination with pembrolizumab reversed programmed death receptor 1 (PD-1) blockade resistance in advanced melanoma. 

. 2020;8. doi:10.1136/jitc-2020-SITC2020.0304

CMP-001 in combination with pembrolizumab in subjects with recurrent or metastatic head and neck squamous cell carcinoma. ClinicalTrials.gov. Updated May 17, 2021. Accessed May 20, 2021. 

https://clinicaltrials.gov/ct2/show/NCT04633278

Articles

The safety and efficacy of the combination of vidutolimod and nivolumab is currently under investigation in patients with PD-1–refractory advanced melanoma.

Vidutolimod/Nivolumab Under Evaluation in PD-1–Refractory Advanced Melanoma

Daiichi Sankyo Inc. is collaborating with Guardant Health Inc. to develop a companion diagnostic for fam-trastuzumab deruxtecan-nxki (Enhertu), which is being studied to treat patients with advanced metastatic 

-mutated non‒small cell lung cancer (NSCLC).

“Lung cancer is an area where we have more and more specific therapies so identifying patients selectively for a specific therapy becomes more and more important,” said Gilles Gallant, BPharm, PhD, FOPQ, senior vice president, global head in oncology development, oncology R&D, at Daiichi Sankyo, told 

. “At diagnosis, a tumor biopsy is done, but for second-line treatment, there are risks for the patient in taking a biopsy. But we have to make sure patients have the mutation. This is extremely important for the drug to work.”

A blood-based assay would be faster, simpler, and less invasive for the patient, Gallant added. “Now, we need to demonstrate that those assays are good, if not better, than taking a piece of the tumor.”

Trastuzumab deruxtecan is currently being studied as a second-line treatment for patients with 

-mutated metastatic NSCLC after at least 1 regimen of prior anticancer therapy that must have contained a platinum-based chemotherapy drug.

Patients in the global phase 2 DESTINY-Lung02 trial (NCT04644237) will be randomized in a 2:1 ratio to receive either the 5.4 mg/kg or 6.4 mg/kg dose of trastuzumab deruxtecan. The primary end point of the study is objective response rate (ORR), as assessed by blinded independent central review (ICR). Secondary end points include disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), investigator-assessed ORR, overall survival (OS), pharmacokinetics, time to response, quality of life, and safety.

Trastuzumab deruxtecan has been approved by the FDA to treat patients with 

locally advanced or metastatic HER2-positve gastric or gastroesophageal junction adenocarcinoma

 who had previously received a trastuzumab (Herceptin)-based regimen.

Investigators presented an interim analysis from the phase 2 DESTINY-Lung01 trial (NCT03505710) at the 2020 ASCO Virtual Scientific Program. Data were presented from 42 patients with 

-mutant unresectable and/or metastatic nonsquamous NSCLC.

The primary end point of confirmed ORR, which was assessed by ICR, was 61.9% (95% CI, 45.6%-76.4%) with trastuzumab deruxtecan monotherapy (6.4 mg/kg). Patients who received the antibody-drug conjugate achieved a DCR of 90.5% (95% CI, 77.4%-97.3%), with a median PFS of 14.0 months (95% CI, 6.4-14.0). The median DOR and OS had not yet been reached at the time of data cutoff.

The DESTINY-Lung01 trial used data from tissue testing to confirm 

 mutation status, Gallant said. “However, we wanted a much easier test to identify those patients. A blood test opens up an easier way to identify potential patients for this agent.”

Guardant360 CDx is an FDA-approved liquid biopsy that provides comprehensive genomic profiling results to guide treatment in all solid tumors. “It is approved for 55 genes for tumor profiling, which gives the physician a broad view of each patient to use in therapy selection,” Justin Odegaard, MD, PhD, vice president of clinical development at Guardant Health, told 

“A companion diagnostic indication for FDA is built around 2 basic things. First, is the test accurate and analytically correct?” Odegaard questioned. “And second, do patients identified by the test respond to the drug?” Odegaard further added that the goal for this specific companion diagnostic approval is to improve overall patient access to optimal therapy. “We are working to help physicians determine who is eligible to receive trastuzumab deruxtecan,” Odegaard noted.

Guardant360 CDx is also an approved companion diagnostic for osimertinib (Tagrisso) to identify patients with NSCLC who have tumors that harbor 

The test is also being pursued as a companion diagnostic for other therapies to treat patients with NSCLC. Amgen and Guardant Health are collaborating to develop a test for sotorasib for patients with NSCLC who have the 

The FDA is currently reviewing a new drug application for sotorasib

 for this indication under its Real-Time Oncology Review (RTOR) pilot program. The application has a received a priority review designation.

Janssen Biotech and Guardant worked together to develop a companion diagnostic for 

, an investigational EGFR/MET bispecific antibody that has recently received FDA approval for use in adult patients with NSCLC who harbor 

regulatory agency gave the green light to Guardant360 CDx

 to determine which patients may derive benefit from amivantamab after progressing on, or after platinum-based chemotherapy.

Guardant Health announces collaboration with Daiichi Sankyo to develop Guardant360 CDx as a companion diagnostic for Enhertu in advanced metastatic non‒small cell lung cancer. News release. Guardant Health. April 27, 2021. Accessed May 25, 2021. 

DESTINY-Lung02 phase 2 trial of Enhertu initiated in patients with HER2 mutated non‒small cell lung cancer. News release. Daiichi Sankyo. March 29, 2021. Accessed May 25, 2021. 

Enhertu. Prescribing information. Daiichi Sankyo; 2021. Accessed May 18, 2021. 

Smit EF, Nakagawa K, Nagasaka M, et al. Trastuzumab deruxtecan (T-DXd; DS-8201) in patients with HER2-mutated metastatic non–small cell lung cancer (NSCLC): interim results of DESTINY-Lung01. 

. 2020;38(suppl 15):9504. doi:10.1200/JCO.2020.38.15_suppl.9504

Guardant Health announces collaboration with Amgen to develop a global liquid biopsy companion diagnostic for AMG 510 KRAS G12C inhibitor. News release. Guardant Health. January 13, 2020. Accessed May 25, 2021. 

FDA grants sotorasib priority review designation for the treatment of patients with KRAS G12C mutated locally advanced or metastatic non‒small cell lung cancer. News release. Amgen. February 16, 2021. Accessed May 25, 2021. 

Guardant Health announces collaboration with Janssen to develop liquid biopsy companion diagnostic. News release. Guardant Health. July 8, 2020. Accessed May 18, 2021. 

Guardant360 CDx receives FDA approval as companion diagnostic for Janssen’s RYBREVANT (amivantamab-vmjw) for use in patients with advanced non-small cell lung cancer with EGFR exon 20 insertion mutations. News release. May 21, 2021. Accessed May 25, 2021. 

Daiichi Sankyo Inc. is collaborating with Guardant Health Inc. to develop a companion diagnostic for fam-trastuzumab deruxtecan-nxki, which is being studied to treat patients with advanced metastatic HER2-mutated non‒small cell lung cancer.

Daiichi Sankyo and Guardant Health Team Up for Companion Diagnostic for Trastuzumab Deruxtecan in Advanced NSCLC

The University of Texas MD Anderson Cancer Center and the immuno-oncology company TriSalus™ Life Sciences announced a strategic research collaboration to evaluate SD-101, an investigational toll-like receptor 9 (TLR9) agonist, in combination with checkpoint inhibitors for the treatment of patients with pancreatic cancer and hepatocellular carcinoma (HCC).

The initial study of the collaboration will enroll patients with uveal melanoma–related liver metastases, with other studies planned in metastatic pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer. Additional trials in HCC and locally advanced PDAC are being developed.

“Tumors in the pancreas and liver are notoriously difficult to treat effectively, and these patients need new therapeutic options. Our collaboration with TriSalus provides a unique opportunity to evaluate immunotherapy in combination with a novel delivery approach,” said Sapna Patel, BA, MD, an associate professor, uveal melanoma program director, fellowship program director, and director of online media in the Department of Melanoma Medical Oncology at The University of Texas MD Anderson Cancer Center.

 “We look forward to our work together to advance new treatments aimed at improving clinical outcomes and the lives of our patients.”

The TLR9 agonist is thought to bind to the TLR9 receptors present on suppressive immune cells, including myeloid-derived suppressor cells and antigen-presenting immune cells.

 These receptors contribute to the innate immune system and provide a bridge to adaptive immunity. As such, activating TLR9 may prime immune cells to promote antitumor T-cell function.

SD-101 is delivered intravascularly via TriSalus™ Life Sciences’s FDA cleared, proprietary Pressure-Enabled Drug Delivery™ (PEDD™) technology. PEDD™ offers the potential to deliver SD-101 in a way not previously possible with standard direct injection delivery.

Small prospective and retrospective studies reported that more therapy was able to be delivered into the vasculature of liver metastases and pancreatic solid tumors with PEDD™ technology vs standard end-hole microcatheters.

 The novel approach has the potential to overcome barriers of the tumor microenvironment, such as abnormal vascularity, interstitial fluid pressure, and solid stress.

Moreover, this approach could make treating certain solid tumor malignancies, such as pancreatic cancer and HCC, more feasible.

Previously, SD-101 in combination with pembrolizumab (Keytruda) demonstrated early efficacy signals and tolerability in phase 1b/2 studies for patients with PD-1 inhibitor–naïve recurrent or metastatic head and neck squamous cell carcinoma (NCT02521870)4, PD-1/PD-L1 inhibitor–resistant advanced or metastatic melanoma (NCT02521870)5, and PD-1/PD-L1 inhibitor–naïve advanced melanoma (NCT02521870)6.

Notably, these data suggest that SD-101 can stimulate innate immune cells and favorably program T cells to enhance responses to checkpoint inhibitors.

“We’re pleased to collaborate with MD Anderson in pursuit of our collective goal to improve outcomes for patients with tumors of the liver and pancreas. The goal of these studies is to augment the potential of existing therapies through novel drug delivery technology and to investigate the strategic modulation of immune microenvironments with investigational candidate SD-101,” said Steven Katz, MD, chief medical officer of TriSalus™ Life Sciences.

TriSalus Life Sciences and MD Anderson announce strategic research collaboration to evaluate treatment of solid tumors. Business Wire. News release. April 8, 2021. Accessed May 21, 2021. 

SD-101 an investigational TLR9 agonist. TriSalus™ Life Sciences. 2021. Accessed May 21, 2021. https://trisaluslifesci.com/pipeline-overview/sd-101/.

Proprietary drug delivery technology. TriSalus™ Life Sciences. 2021. Accessed May 21, 2021. 

https://trisaluslifesci.com/drug-delivery/

Cohen EEW, Nabell L, Wong DJL, et al. Phase 1b/2, open label, multicenter study of intratumoral SD-101 in combination with pembrolizumab in anti-PD-1 treatment naïve patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). 

. 2019;37(suppl 15):6039. doi:10.1200/JCO.2019.37.15_suppl.6039

Amin A, Milhem MM, Long GV, et al. Phase 1b/2, open label, multicenter, study of the combination of SD-101 and pembrolizumab in patients with advanced/metastatic melanoma resistant to anti-PD-1/PD-L1 therapy. 

. 2019;37(suppl 15):9555. doi:10.1200/JCO.2019.37.15_suppl.9555

Milhem MM, Long GV, Hoimes CJ, et al. Phase 1b/2, open label, multicenter, study of the combination of SD-101 and pembrolizumab in patients with advanced melanoma who are naïve to anti-PD-1 therapy. 

. 2019;37(suppl 15):9534. doi:10.1200/JCO.2019.37.15_suppl.9534

The University of Texas MD Anderson Cancer Center and the immuno-oncology company TriSalus™ Life Sciences announced a strategic research collaboration to evaluate SD-101 in pancreatic cancer and hepatocellular carcinoma.

Pipeline Report: May 2021

Articles

Vidutolimod/Nivolumab Under Evaluation in PD-1–Refractory Advanced Melanoma

Daiichi Sankyo and Guardant Health Team Up for Companion Diagnostic for Trastuzumab Deruxtecan in Advanced NSCLC