SYS6002 (CRB-701) A Next-Generation Nectin-4 Targeting Antibody Drug Conjugate Continues to Demonstrate Encouraging Safety and Efficacy Observed in Patients with Nectin-4 Positive Tumors in a Clinical Update Presented at ASCO 2024

Rhea-AI Summary

Corbus Pharmaceuticals announced promising clinical data for SYS6002 (CRB-701), a Nectin-4 targeting antibody drug conjugate, during the ASCO 2024 conference.

The Phase 1 trial has enrolled 37 patients since January 2024, with 25 evaluated for efficacy. SYS6002 showed a 44% ORR and 78% DCR in metastatic urothelial cancer (mUC), and a 43% ORR and 86% DCR in cervical cancer at doses ≥ 1.2 mg/Kg.

No dose-limiting toxicities were observed up to 4.5 mg/Kg. Notable adverse events included three cases of skin rash and one instance of grade 1 neuropathy, all resolved. Pharmacokinetic data demonstrated lower free MMAE levels than enfortumab vedotin across all doses.

The trial continues to show SYS6002's safety and efficacy, with the U.S. clinical study expected to complete in Q4 2024, with data presentation in Q1 2025.

Positive

• 44% ORR and 78% DCR in mUC at doses ≥ 1.2 mg/Kg.
• 43% ORR and 86% DCR in cervical cancer at doses ≥ 1.2 mg/Kg.
• No dose-limiting toxicities observed up to 4.5 mg/Kg.
• Lower free MMAE levels than enfortumab vedotin across all doses.
• No grade 4 or 5 adverse events reported.
• Confirmed partial and stable disease responses at multiple dose levels.

Negative

• Three cases of skin rash, including one grade 3.
• One instance of grade 1 neuropathy.
• Two grade 3 corneal disorders reported.
• Over 50% of patients had corneal disorders or dry eye at baseline.

Insights

Medical Research Analyst

The clinical update on SYS6002 (CRB-701), a next-generation Nectin-4 targeting antibody-drug conjugate (ADC), offers an insightful look into its evolving safety and efficacy profile. From a medical research perspective, the 44% ORR and 78% DCR in metastatic urothelial cancer (mUC) and 43% ORR and 86% DCR in cervical cancer are promising indicators of the drug's efficacy. Moreover, the absence of dose-limiting toxicities (DLTs) up to 4.5 mg/Kg suggests a favorable safety profile.

The emerging clinical pharmacology data is particularly noteworthy. The report indicates a dose-proportional increase in ADC and MMAE exposure up to 2.7 mg/Kg, with a leveling off beyond this dose. The lower average levels of free MMAE compared to enfortumab vedotin are especially significant, as they suggest a potentially better safety profile. Given that SYS6002 (CRB-701) is well-tolerated with mainly grade 1 or 2 adverse events (AEs) and no new serious adverse events (SAEs) since the January update, the data support the continued development of this ADC.

For retail investors, this clinical update offers a promising outlook on the drug's potential, particularly in terms of safety and efficacy. However, it is important to consider that these are still early-stage results and further data, particularly from larger patient cohorts and longer follow-ups, are necessary to confirm these findings.

Oncology Doctor

From an oncology perspective, the data on SYS6002 (CRB-701) is compelling. The drug targeting Nectin-4 positive tumors shows an overall response rate (ORR) and disease control rate (DCR) that are quite impressive for early-phase clinical trials. Specifically, an ORR of 44% in mUC and 43% in cervical cancer could indicate meaningful clinical benefits for patients who have failed or are intolerant to standard treatments. This is particularly important in these patient populations, where treatment options are often limited.

The safety profile of SYS6002 (CRB-701), with manageable adverse events and no grade 4 or 5 toxicities, is another positive aspect. The occurrence of skin rashes and neuropathy are common in this class of drugs, but the fact that these were all resolved without dose interruption is reassuring. Such a safety profile may enhance patient compliance and overall quality of life during treatment.

For investors, these results suggest that SYS6002 (CRB-701) has a strong potential to advance in clinical trials and could become a viable treatment option in the oncology market. The differentiation from enfortumab vedotin due to lower free MMAE levels could also position this drug favorably in a competitive landscape.

Financial Analyst

From a financial perspective, the promising clinical data for SYS6002 (CRB-701) is likely to positively impact Corbus Pharmaceuticals' stock. The high ORR and DCR rates in both mUC and cervical cancer suggest that the drug has significant potential market applicability. The absence of dose-limiting toxicities and serious adverse events further strengthens the case for continued investment in its development.

The differentiation from existing treatments like enfortumab vedotin, particularly in terms of lower free MMAE levels, could position SYS6002 (CRB-701) as a superior option in the Nectin-4 ADC market. This could potentially lead to increased market share and revenue for Corbus Pharmaceuticals if the drug progresses successfully through clinical trials.

For retail investors, the ongoing positive clinical developments suggest that Corbus Pharmaceuticals is on a promising trajectory. However, it's essential to remain mindful of the inherent risks in biopharmaceutical development, including the potential for unexpected adverse events or regulatory hurdles. Nevertheless, the current data supports a cautiously optimistic outlook for the company's future prospects.

• An additional 19 patients have been enrolled since January 2024 bringing the total to 37 of whom 25 were evaluable for efficacy
  
• SYS6002 (CRB-701) demonstrated 44% ORR and 78% DCR in mUC and 43% ORR and 86% DCR in cervical cancer to date at doses ≥ 1.2mg/Kg
• No dose limiting toxicities (DLTs) have been observed to date in doses up to and including 4.5 mg/Kg (cohort 7)
• Three cases of skin rash (including one grade 3) and one case of grade 1 neuropathy seen to date; all were resolved
• Early PK data demonstrate consistently lower levels of free MMAE than enfortumab vedotin across all doses in study including 4.5 mg/Kg
  

NORWOOD, Mass., June 01, 2024 (GLOBE NEWSWIRE) -- Corbus Pharmaceuticals Holdings, Inc. (NASDAQ: CRBP) (“Corbus” or the “Company”), announced today, that the Poster [#296] Clinical Update Related to the First-In-Human Trial of SYS6002 (CRB-701), A Next-Generation Nectin-4 Targeting Antibody Drug Conjugate, has been presented at American Society of Clinical Oncology (ASCO) Annual Conference by Dr. Jian Zhang, Chief Physician (Oncology), Deputy Director of Administration, Clinical director of Phase 1 Centre, Fudan University Shanghai Cancer Center.

The Phase 1 study, sponsored by CSPC Pharmaceuticals Group Limited in China, is evaluating the safety and tolerability of SYS6002 (CRB-701) in patients with advanced solid tumors who have failed or were intolerant to standard treatment. Patients were enrolled based on Nectin-4 staining with the exception of metastatic urothelial cancer (mUC) patients who were considered to be Nectin-4 positive. The poster presents data as of the end of April 2024 from the dose escalation spanning 7 dose levels (0.2, 0.6, 1.2, 1.8, 2.7, 3.6 & 4.5 mg/Kg Q3W) and PK cohorts (2.7 and 3.6 mg/Kg).

“This latest data update provides additional insight following the initial observations from our partner CSPC’s January 2024 data cut,” said Dr. Dominic Smethurst, Chief Medical Officer at Corbus. “This larger set of patient data, along with additional confirmed responses, increases our confidence that CRB-701 is clinically active. Similarly, we find the emerging safety data reassuring with its low rates of skin rash and peripheral neuropathy and very few grade 3 adverse events. Lastly, it is satisfying to observe the translation from the pre-clinical to the clinic of significantly lower levels of free MMAE due to the stability of this ADC construct.”

Emerging clinical safety profile:

• SYS6002 (CRB-701) was generally well tolerated with mainly grade 1 or 2 AEs.
• No DLTs or grade 4 or 5 AEs have been observed to date.
• Anemia and eye-related treatment emergent AEs (TEAEs) were the most common.
• One patient exhibited a grade 3 rash which lasted for eight days and did not result in a reduction or interruption in dosing (2.7 mg/Kg). Two milder cases of skin rash were recorded (grade 1 and grade 2). Both also resolved with no need for change or interruption in dosing.
• No new drug-related SAEs have been encountered since the January 2024 data update.
• To date, a single case of peripheral neuropathy (grade 1) has been reported (numb hands) associated with hypokalemia (grade 3). It resolved in parallel with the hypokalemia after ten days of combined oral and/or parenteral K⁺ replacement therapy.
• Two grade 3 corneal disorders were reported in patients who received 2.7 mg/Kg and 3.6 mg/Kg, respectively. Preventative eye measures have been introduced and no such cases have been seen so far at the 4.5 mg/Kg dose. Over 50% of patients enrolled had corneal disorders or dry eye at baseline.
  

Emerging efficacy profile:

• Anti-tumor responses across multiple doses continue to be observed, with the first confirmed stable disease at 0.6 mg/Kg and the first confirmed partial response (PR), at 1.2 mg/Kg.
• To date, SYS6002 (CRB-701) resulted in 44% overall response rate (ORR) and 78% disease control rate (DCR) in mUC (n=9, 4 PRs, 1 unconfirmed) and 43% ORR and 86% DCR in cervical cancer (n=7, 3PRs, 1 unconfirmed).
• For all the tumor types combined at doses ≥ 2.7 mg/Kg, SYS6002 (CRB-701) resulted in 40% ORR and 73% DCR (n=15, 6 PRs, 2 unconfirmed). An additional PR was confirmed at the 1.2 mg/Kg for an mUC patient. Two unconfirmed PR’s reported at ASCO-GU have since been confirmed.
  

Emerging clinical pharmacology:

• After a single IV infusion of SYS6002 (CRB-701), the exposure of ADC and MMAE generally increased in a dose proportional manner up to 2.7 mg/Kg.
• Dosing beyond the 2.7 mg/Kg level showed a leveling off of free MMAE.
• All dose levels studied to date are showing lower average levels of free MMAE than enfortumab vedotin at the reference dose (1.25 mg/Kg dosed on days 1, 8 and 15 of a 28-day cycle).
  

“We are encouraged by this latest data release,” said Dr. Yuval Cohen, Chief Executive Officer at Corbus. “The corresponding U.S. clinical study is progressing well and is expected to be on schedule for completion in Q4 with data presentation in Q1 2025. We believe the emerging dataset positions CRB-701 to be a differentiated Nectin-4 ADC. We look forward to generating more data in a number of specific Nectin-4 solid tumors.”

About CRB-701
CRB-701 (SYS6002) is a next-generation antibody drug conjugate (ADC) targeting Nectin-4 with a third-generation, site-specific cleavable linker and a homogenous drug antibody ratio of 2, using MMAE as the payload. Nectin-4 is a clinically validated, tumor-associated antigen in urothelial cancer. SYS6002 (CRB-701) is currently being explored in a dose escalation on a Q3W schedule, with a view to reducing free MMAE concentrations in plasma, reducing the associated toxicities that are believed to dose limit the Nectin-4 ADC PADCEV^® (enfortumab vedotin). Additionally, by administering SYS6002 (CRB-701) on a Q3W schedule there is an opportunity to increase clinical convenience and patient compliance.

About Corbus
Corbus Pharmaceuticals Holdings, Inc. is a precision oncology company with a diversified portfolio and is committed to helping people defeat serious illness by bringing innovative scientific approaches to well understood biological pathways. Corbus’ pipeline includes CRB-701, a next-generation antibody drug conjugate that targets the expression of Nectin-4 on cancer cells to release a cytotoxic payload, CRB-601, an anti-integrin monoclonal antibody which blocks the activation of TGFβ expressed on cancer cells, and CRB-913, a highly peripherally restricted CB1 inverse agonist for the treatment of obesity. Corbus is headquartered in Norwood, Massachusetts. For more information on Corbus, visit corbuspharma.com. Connect with us on Twitter, LinkedIn and Facebook.

Forward-Looking Statements
This press release contains certain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934 and Private Securities Litigation Reform Act, as amended, including those relating to the Company's trial results, product development, clinical and regulatory timelines, including timing for completion of trials and presentation of data, market opportunity, competitive position, possible or assumed future results of operations, business strategies, potential growth opportunities and other statement that are predictive in nature. These forward-looking statements are based on current expectations, estimates, forecasts and projections about the industry and markets in which we operate and management's current beliefs and assumptions.

These statements may be identified by the use of forward-looking expressions, including, but not limited to, “expect,” “anticipate,” “intend,” “plan,” “believe,” “estimate,” “potential,” “predict,” “project,” “should,” “would” and similar expressions and the negatives of those terms. These statements relate to future events or our financial performance and involve known and unknown risks, uncertainties, and other factors on our operations, clinical development plans and timelines, which may cause actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. Such factors include those set forth in the Company's filings with the Securities and Exchange Commission. Prospective investors are cautioned not to place undue reliance on such forward-looking statements, which speak only as of the date of this press release. The Company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.

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INVESTOR CONTACT:

Sean Moran
Chief Financial Officer
Corbus Pharmaceuticals
smoran@corbuspharma.com

Bruce Mackle
Managing Director
LifeSci Advisors, LLC
bmackle@lifesciadvisors.com

FAQ

What are the latest results for CRBP's SYS6002 (CRB-701) in mUC patients?

SYS6002 demonstrated a 44% overall response rate (ORR) and 78% disease control rate (DCR) in metastatic urothelial cancer (mUC) patients at doses ≥ 1.2 mg/Kg.

How did SYS6002 (CRB-701) perform in cervical cancer patients?

SYS6002 achieved a 43% overall response rate (ORR) and 86% disease control rate (DCR) in cervical cancer patients at doses ≥ 1.2 mg/Kg.

Were there any dose-limiting toxicities observed with SYS6002 (CRB-701)?

No dose-limiting toxicities were observed up to 4.5 mg/Kg of SYS6002 (CRB-701).

What adverse events were reported in the SYS6002 (CRB-701) trial?

Reported adverse events included three cases of skin rash, one instance of grade 1 neuropathy, and two grade 3 corneal disorders. All cases resolved without major issues.

How did SYS6002 (CRB-701) compare with enfortumab vedotin in terms of free MMAE levels?

SYS6002 demonstrated lower levels of free MMAE compared to enfortumab vedotin across all studied doses.

When will the U.S. clinical study data for SYS6002 (CRB-701) be presented?

The U.S. clinical study data for SYS6002 (CRB-701) is expected to be presented in Q1 2025.