2018 AACR Annual Meeting Highlights


Highlights from the 2018 AACR Annual Meeting.

Welcome to OncLive News Network! I’m Gina Columbus.

Initial findings from the phase III CheckMate-227 trial, presented at the meeting, demonstrated that the combination of nivolumab and ipilimumab more than tripled the 1-year progression-free survival rate versus chemotherapy for treatment-naïve patients with non—small cell lung cancer with high tumor mutation burden. The results were also published in the New England Journal of Medicine.

The 1-year PFS rate was 43% for patients with high TMB who were treated with the immunotherapy combination versus 13% for those assigned to platinum-doublet chemotherapy. The median PFS was 7.2 months versus 5.5 months, respectively, representing a 42% reduction in risk of disease progression or death.

The combination was well tolerated and safety was similar to previous results with the therapies.

The objective response rate was 45.3% with the immunotherapy combination versus 26.9% with chemotherapy. Among responders, 68% had an ongoing response after 1 year with nivolumab/ipilimumab, versus 25% with chemotherapy.

Overall survival data are not yet mature, but are said to be encouraging. Additionally, the median PFS did not favor the combination in the overall population though the combination was associated with a higher 1-year PFS rate.


BLU-667, a next-generation tyrosine kinase inhibitor, appeared to be well tolerated and had broad clinical benefit among patients with advanced, RET-altered solid tumors who progressed on prior therapies.

According to phase I data of the ARROW trial presented at the conference, RET is a rare driver of multiple, diverse tumor types including more than 60% of medullary thyroid cancers, approximately 10% of papillary thyroid tumors, about 1% to 2% of non-small cell lung cancers, and only about 1% of patients with esophageal cancer, breast cancer, melanoma, colorectal cancer, and leukemia.

In the open-label, first-in-human, phase I study, BLU-667 demonstrated broad antitumor activity with a best overall response rate of 37% in patients with advanced solid tumors with RET alterations who received doses greater than 60 mg and had at least 1 post-baseline response assessment. In particular, patients with NSCLC and MTC had a best ORR of 50% and 40%, respectively. Among those with RET fusions and mutations, the ORR was 45%.

Of the 40 evaluable patients, 1 experienced a complete response, 17 had partial responses, 20 patients achieved stable disease, and 2 patients had progressive disease. The maximum-tolerated dose was not reached.

BLU-667 appeared to be well-tolerated, with grade 1 constipation as the most common adverse event. The researchers recorded 3 dose-limiting toxicities and no grade 4 to 5 AEs occurred. At of the data cutoff, 41 of 51 RET-altered patients remained on treatment.


In non—small cell lung cancer, a pilot study found that neoadjuvant treatment with nivolumab demonstrated a 45% major pathologic response rate in patients with resectable stage I to III disease irrespective of PD-L1 expression.

The PD-1 inhibitor also was associated with a tolerable safety profile and was not associated with any delays in surgery.

At a median follow-up of 12 months, 16 of 20 patients who underwent surgical resection were alive and recurrence-free. Additionally, the 18-month recurrence-free survival rate was 73% and the median RFS had not yet been reached.

Nine of 20 patients achieved a major pathologic response, and 3 patients had a pathologic complete response. Of the 21 patients with evaluable radiographic results, 2 had a partial response, 18 had stable disease, and 1 had disease progression. Pathological down-staging occurred in 8 of 20 patients who underwent resection.

Though major pathologic responses were observed in patients’ tumors regardless of PD-L1 expression, tumor mutational burden was a closer factor in predicting response.


Preliminary results presented at the meeting showed that combination therapy with CMP-001, an intratumoral toll-like receptor 9 agonist, and pembrolizumab had clinical activity in reversing PD-1 checkpoint inhibition resistance in patients with metastatic melanoma.

While pembrolizumab is the standard of care for this patient population, over 50 percent of patients with metastatic melanoma develop resistance.

In the ongoing study, researchers evaluated the combination use of CMP-001 with checkpoint inhibition in patients with advanced melanoma who had either not responded to or had progressed during prior anti—PD-1 therapy.

Data showed that among the intent-to-treat population, the objective response rate was 22%, including 2 complete responses and 13 partial responses. The ORR was 23% in those who received treatment weekly and 15% in those who were given the regimen every 3 weeks.

Enrollment into an expansion phase of the trial is ongoing, and clinical investigation in other tumor types is underway.


Finally, treatment with crizotinib elicited an objective response rate of 50% for patients with ALK-positive advanced, inoperable inflammatory myofibroblastic tumors, according to phase II findings presented at the meeting.

In the EORTC 90101 trial, which was also known as the CREATE study, 12 patients with ALK-positive IMT were evaluable for response to crizotinib. Of these patients, 2 experienced a confirmed complete response and 4 had a confirmed partial response. The remaining 6 patients had either stable disease or a non-confirmed PR, leading to an overall disease control rate of 100% for crizotinib.

At the data cutoff in November 2017, 4 patients with ALK-positive IMT continued to respond to treatment with crizotinib. The median duration of response was 9 months. The 1-year PFS rate was 73.3% and the 2-year PFS rate was 48.9%. Additionally, both the 1-year and 2-year overall survival rates were 81.8%.

Crizotinib is currently approved by the FDA for the treatment of patients with ALK-positive or ROS1-positive non—small cell lung cancer.


That’s all for today.

Thank you for watching OncLive News Network! I’m Gina Columbus.

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