ASCO: With hopes high, Regeneron misses mark with just one complete response in solid tumor trial so far

With analysts looking for a meaningful increase in the number of responses for Regeneron's phase 1/2 solid tumor trial, a fresh data slice shows just one complete response across 94 patients. 

Regeneron’s costimulatory bispecific antibody REGN7075 is being tested in patients with advanced solid tumors in the split-phase trial, according to new data shared May 23. Regeneron previously presented preliminary phase 1/2 data on a combination of REGN7075 and the biopharma's Libtayo in November 2022. At that time, out of 18 patients treated with up to 30 mg of REGN7075, only one patient receiving 1 mg achieved a partial response.

Now, Regeneron says that out of 94 evaluable patients, just one complete response and two partial responses were recorded. Patients received a REGN7075 monotherapy lead-in dose, followed by the investigational combination therapy. The new data show a 6% (three patients) overall response rate (ORR) and 29% (15 patients) at a disease control rate (DCR).  

Among the 94 patients, 65% (61) had microsatellite stable colorectal cancer (MSS CRC), a form of cancer that has historically been unresponsive to immunotherapy. The MSS CRC data will be presented during an oral presentation at the American Society of Clinical Oncology (ASCO) annual meeting, which begins next week. 

Among the MSS CRC subset, 51 patients were treated at the undisclosed active dosing level. Among those 51 patients, a subset of 15 did not have liver metastases. That group includes the three patients who responded, bringing the subset’s ORR to 20%. And, in 36 patients who did have liver metastases, three patients had stable disease and all responders were without liver metastases at data cutoff.

“The presence of liver metastases is increasingly being recognized as a sign of a tougher immune suppressed environment to overcome,” Israel Lowy, M.D., Ph.D., senior vice president of translational and clinical oncology at Regeneron, told Fierce Biotech. “Since then, we actually have seen a response in a patient with a liver metastasis—it's not part of the data cut being presented.”

“What we are most excited about is that we're actually seeing responses in this group of patients that we know the response rate with the PD-1 alone is essentially zero,” Lowy added. “So, it's a start.”

Despite the low number of responses, Regeneron continues to tout the agent’s combination potential for specific patient groups that don't respond to standard treatments. 

Ahead of the expected ASCO data release, analysts from Leerink Partners had hoped to see therapeutic doses inducing strong responses without a high rate of unmanageable adverse events or deaths. If achieved, Leerink Partners said its confidence would increase in Regeneron’s costimulatory bispecifics platform, a method designed to bridge T-cells to cancer cells and change CD28 signaling to boost anti-tumor activity in combination with the PD-1 inhibitor Libtayo or a CD3 bispecific.   

Leerink Partners was also hoping to see more patients evaluable at this ASCO data cutoff with additional tumor types, a longer time on the drug and higher dose levels of REGN7075. Regeneron is expected to boost dosing up to 900 mg, eventually. 

"We’re hoping to see a meaningful increase in the number of responses and possibly an update that the study will move into the dose expansion phase of the trial," the analysts wrote. 

But the firm's meaningful increase criteria may not have been met with this cut.

On the safety side, treatment-related adverse events (TRAEs) led to discontinuation in 5% of patients, while three other patients discontinued due to grade 2 infusion-related reactions.

Safety was assessed in 84 remaining patients, with the investigational combo demonstrating an “acceptable safety profile” and the maximum tolerated dose not yet reached, according to Regeneron’s May 23 release. The safety data shared had a different cutoff date than the new efficacy data, though the data set includes patients through the same dose level from which efficacy is reported, a Regeneron spokesperson told Fierce Biotech.

Treatment-emergent adverse events—events that occur after the start of treatment—of any grade occurred in 98% of patients.

Meanwhile, TRAEs occurred in 90% of patients, with 7% of cases reported as grade 3 or 4 events, which are severe or life-threatening, respectively. The rest of the events were classified as lower grades. The most common low-grade events (58%) were infusion-related reactions that were manageable with premedication and dosing adjustments.

As of the safety data cutoff, there were no dose-limiting toxicities and no treatment-related deaths.

In 2023, two deaths occurred in a Regeneron trial testing out a separate costimulatory program, a prostate cancer bispecific dubbed REGN5678, or nezastomig. The asset is designed to bind to CD28 on cytotoxic T-lymphocytes and PSMA on tumor cells. The company amended its study protocol after the deaths, lowering the dose levels of Libtayo and other immunotherapy modalities.    

The immune-mediated adverse events prompted Regeneron to “slow down a little bit,” said Lowy, who added that the company worked to “separate the immune mediated adverse events from the clinical toxicity.”

“So far, we have not observed these kinds of immune mediated adverse events with the EGFR by CD28 costim,” Lowy said, referring to REGN7075. The company also has a third costim candidate, dubbed REGN5668, a MUC16xCD28 for ovarian cancer.

“We're doing multiple ones because we don't know what the rules are for how this class of agents will behave,” Lowy explained. “And I think what we’ll find out is that there are ways in which each one might be a little unique.”

Regeneron said the new solid tumor results are positive, emphasizing the fact that the patient population is a group that has exhausted standard treatment options.

“Microsatellite stable colorectal cancer has historically been unresponsive to immunotherapy,” Neil Segal, M.D., Ph.D., research director of gastrointestinal oncology at Memorial Sloan Kettering Cancer Center and a trial investigator, said in Regeneron’s release. “This combination is one of the first immunotherapy regimens to show clinical activity in microsatellite stable colorectal cancer, and we are excited to advance this trial in additional tumor types.”

The open-label trial is still recruiting patients with metastatic and locally advanced solid tumors, with an expected enrollment of 769 participants, according to The study includes an ongoing phase 1 dose-escalation portion and a phase 2 dose-expansion period and has a primary completion date slated for August 2026.

The company is exploring how REGN7075 acts not only with Libtayo but also other combinations such as CD3 biospecifics or other chemotherapies, Lowy said.

He also said the company thinks some of the CAR-T programs recently acquired from 2seventy bio in January may benefit from the addition of a costimulatory agent.

Editor's note: This article was updated at 10:15 a.m. ET on May 24 to clarify only a specific subgroup of data will be presented as ASCO.