CARGO Therapeutics to Discontinue FIRCE-1 Phase 2 Study of Firi-cel; Advances Remaining Programs While Evaluating Strategic Options

Rhea-AI Summary

CARGO Therapeutics (NASDAQ: CRGX) announced the discontinuation of FIRCE-1, its Phase 2 clinical study of firi-cel for large B-cell lymphoma patients resistant to CD19 CAR T-cell therapy. The decision follows an ad hoc analysis showing unfavorable benefit-risk profile, with data from 51 patients showing 77% overall response rate and 43% complete response rate, but only 18% durability at three months.

The study revealed concerning safety data, with 18% of patients developing severe immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS), including grade 4 and 5 serious adverse events. In response, CARGO will implement a 50% workforce reduction to preserve cash. The company will continue advancing CRG-023, its tri-specific CAR T, into Phase 1 trials and develop its allogeneic platform while evaluating strategic options. With $368.1 million in preliminary cash as of December 31, 2024, CARGO expects to extend its runway into mid-2028.

Positive

• Strong cash position of $368.1 million extending runway into mid-2028
• Phase 1 dose escalation study for CRG-023 on track for Q2 2025
• 50% workforce reduction will significantly decrease operational costs

Negative

• Discontinuation of key Phase 2 FIRCE-1 study due to poor efficacy and safety
• Only 18% durability of complete response at three months
• 18% of patients developed severe IEC-HS, including grade 4 and 5 adverse events
• 50% workforce reduction indicates significant operational restructuring

Insights

Oncology Research Analyst

The discontinuation of CARGO's lead program firi-cel marks a critical inflection point for the company, with multiple significant implications for investors. The trial results reveal a concerning safety profile, with 18% of patients experiencing grade 3 or higher IEC-HS, including life-threatening complications. This, combined with the disappointing 18% complete response durability at three months, falls substantially short of current treatment standards for relapsed/refractory LBCL.

The company's strategic response demonstrates prudent financial management. The 50% workforce reduction, while significant, will help extend the cash runway from their $368.1 million reserve into mid-2028. This provides a substantial runway for their remaining pipeline, particularly CRG-023 and their allogeneic platform. The extended cash position offers important flexibility as they evaluate strategic options.

Key considerations for investors:

• The pivot to CRG-023, a tri-specific CAR T therapy, represents a potential differentiation strategy in an increasingly competitive cell therapy landscape
• The allogeneic platform development could provide longer-term value, as off-the-shelf cell therapies remain a highly sought-after approach in the industry
• The extended cash runway provides significant optionality for strategic alternatives, including potential partnerships or M&A opportunities

While this setback is significant, CARGO's strong cash position and pipeline diversification strategy may help mitigate the impact. However, investors should closely monitor the upcoming Phase 1 initiation of CRG-023 in Q2 2025, as this program now becomes critical for the company's near-term value proposition.

• CARGO elects to discontinue FIRCE-1, a Phase 2 clinical study of firicabtagene autoleucel (firi-cel)¹; Company believes results do not support a competitive benefit-risk profile for patients.
• CARGO to implement a workforce reduction of approximately 50%.
• Phase 1 dose escalation study enrollment for CRG-023 on track to initiate in Q2 2025.
  

SAN CARLOS, Calif., Jan. 29, 2025 (GLOBE NEWSWIRE) -- CARGO Therapeutics, Inc. (Nasdaq: CRGX), a clinical-stage biotechnology company advancing next generation, potentially curative cell therapies for cancer patients, today announced that it has elected to discontinue FIRCE-1, a Phase 2 clinical study of firi-cel for patients with large B-cell lymphoma (LBCL) whose disease relapsed or was refractory (R/R) to CD19 CAR T-cell therapy. In-line with this decision, the Company will reduce its workforce to extend cash runway and prioritize the advancement of CRG-023 to Phase 1 proof-of-concept data as well as its novel allogeneic platform.

Based on an ad hoc analysis of FIRCE-1 prompted by recent safety events, the Company believes the results do not support a competitive benefit-risk profile of firi-cel for the intended patient population. While data from 51 patients with at least one post baseline scan demonstrated an overall response rate of 77% and complete response rate (CR) of 43%, the durability of CR at three months was 18%. Safety data indicated 18% of patients developed immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS) that were grade 3 or higher, including grade 4 and grade 5 serious adverse events. IEC-HS is a toxicity that is associated with CAR T-cell therapy and firi-cel in other clinical studies.

The Company is implementing a workforce reduction of approximately 50% to preserve cash. Further, CARGO will continue to advance CRG-023, its tri-specific CAR T, into a Phase 1 dose escalation study and its allogeneic platform to lead vector candidate selection while evaluating its strategic options. With preliminary cash, cash equivalents and marketable securities of $368.1 million⁽²⁾ as of December 31, 2024, the Company expects its cash runway to be extended into mid-2028.

“We are disappointed with these unexpected results from our Phase 2 study. Durability of complete response is an important clinical goal for LBCL patients who are R/R to CD19 CAR T-cell therapy. Combined with a higher-than-expected occurrence and severity of IEC-HS, the data generated so far does not meet our expectations of a competitive benefit-risk profile for patients in the context of available treatment options. Therefore, we believe it is in the best interest of both patients and shareholders to discontinue the study,” said Gina Chapman, President and Chief Executive Officer of CARGO Therapeutics. “While we continue to advance CRG-023 into the clinic this year and progress our novel allogeneic platform, we will also evaluate our strategic options. We are grateful for the patients, caregivers and families who were involved in the FIRCE-1 study, as well as the investigators who partnered closely with us and with whom we look forward to continuing to collaborate. I’d also like to recognize and thank all of our employees at CARGO, including those being impacted by today’s decision, who have worked tirelessly on behalf of patients and made meaningful contributions to our Company’s mission.”

CARGO intends to present an analysis of the FIRCE-1 Phase 2 study at a future medical conference.

About CARGO Therapeutics

CARGO Therapeutics, Inc. is a clinical-stage biotechnology company advancing next-generation, best-in-class, and potentially curative cell therapies for cancer patients. CARGO’s programs, platform technologies, and manufacturing strategy are designed to directly address the limitations of approved cell therapies, including limited durability of effect, safety concerns and availability. CARGO has a focused pipeline that includes its CRG-023 product candidate, a CD19/CD20/CD22 tri-specific CAR T developed using a tri-cistronic construct and designed to address several known causes of relapse, resulting in a potential best-in-class CAR T-cell therapy across a broad range of B-cell malignancies with the goal of providing more patients with a durable complete response. CARGO’s latest program advancement, a novel allogeneic platform, is a universal vector solution designed to limit immune-based rejection and enable durable response of CAR T-cell therapy. The universal allogeneic-enabling vector is intended to be paired with any CAR vector to create an allogeneic CAR T-cell therapy, with the potential to maintain the efficacy, durability, and safety of autologous cell therapy while broadening availability to more people with cancer. CARGO’s leadership and team have significant experience in designing, developing and delivering oncology and cell therapy products. For more information, please visit the CARGO Therapeutics website at https://cargo-tx.com/.

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⁽¹⁾ Firicabtagene autoleucel (firi-cel) is CARGO Therapeutics’ autologous CD22 CAR T-cell product candidate. The underlying CAR of which CARGO exclusively in-licensed from the National Cancer Institute was the construct evaluated by Stanford Medicine in a Phase 1 clinical trial in patients with large B-cell lymphoma whose disease relapsed or was refractory to CD19 CAR T-cell therapy. CARGO’s firi-cel Investigational New Drug application included a comprehensive package in which CARGO performed and demonstrated analytical comparability of CRG-022 produced using the intended commercial process to the CRG-022 produced using the process used for the Stanford Phase 1 clinical trials. CARGO cannot assure that the FDA will agree with its claim of comparability and the sufficiency of the data to support it when it files its Biologics License Application.

⁽²⁾ The Company’s actual consolidated cash, cash equivalents, marketable securities as of December 31, 2024 may differ from this preliminary estimate due to the completion of the Company’s year-end closing and auditing procedures.

Cautionary Note Regarding Forward-Looking Statements

This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. In some cases, you can identify forward-looking statements by terminology such as “aim,” “anticipate,” “assume,” “believe,” “contemplate,” “continue,” “could,” “design,” “due,” “estimate,” “expect,” “goal,” “intend,” “may,” “objective,” “plan,” “positioned,” “potential,” “predict,” “seek,” “should,” “target,” “will,” “would” and other similar expressions that are predictions of or indicate future events and future trends, or the negative of these terms or other comparable terminology. All statements other than statements of historical facts contained in this press release are forward-looking statements. These forward-looking statements include, but are not limited to, statements about: the indication, timing, progress, advancement and results of CARGO’s clinical and preclinical programs; CARGO’s strategic plans for its business and product candidates, including its ongoing evaluation of strategic options; the Company’s expectations and estimates regarding the planned reduction in force and discontinuation of the clinical development of firi-cel; and CARGO’s estimated cash, cash equivalents and marketable securities as of December 31, 2024 and CARGO’s expectations that its current cash, cash equivalents and marketable securities will be sufficient to fund its expected operations into mid-2028. Forward-looking statements are not guarantees of future performance and are subject to risks and uncertainties that could cause actual results and events to differ materially from those anticipated, including, but not limited to, risks and uncertainties related to: the Company’s ability to obtain necessary capital to fund its clinical programs; the early stages of clinical development of the Company’s product candidates and the product candidates involving novel technologies; clinical and preclinical development being a lengthy and expensive process with uncertain outcomes; data from the Company’s clinical trials and preclinical studies, including the performance and characteristics of the Company’s product candidates, including any undesirable side effects or other properties discovered or detected in the Company’s clinical trials and preclinical studies; the Company’s ability to obtain regulatory approval of and successfully commercialize its product candidates, if approved; the Company’s reliance on third-party suppliers and manufacturers, including CROs; the outcomes of future collaboration agreements; and the Company’s ability to adequately maintain intellectual property rights for its product candidates. For a detailed discussion of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to CARGO’s business in general, please refer to the risk factors identified in the Company’s filings with the Securities and Exchange Commission, including but not limited to its Quarterly Report on Form 10-Q for the quarter ended September 30, 2024 filed on November 12, 2024. Any forward-looking statements that the Company makes in this press release are made pursuant to the Private Securities Litigation Reform Act of 1995, as amended, and speak only as of the date of this press release. Except as required by law, the Company undertakes no obligation to publicly update any forward-looking statements, whether as a result of new information, future events or otherwise.

Media Contact:
Denise Powell
denise@redhousecomms.com

Investor Contact:
Jessica Serra
jserra@cargo-tx.com

Laurence Watts
laurence@newstreetir.com

FAQ

What were the key results that led to CRGX discontinuing the FIRCE-1 Phase 2 study?

The study showed only 18% durability of complete response at three months, despite a 77% overall response rate. Additionally, 18% of patients developed severe IEC-HS, including grade 4 and 5 adverse events, leading to an unfavorable benefit-risk profile.

How will the FIRCE-1 study discontinuation impact CRGX's financial position?

CARGO has $368.1 million in cash as of December 31, 2024, and expects to extend its runway into mid-2028, supported by a 50% workforce reduction to preserve cash.

What are CRGX's next steps following the FIRCE-1 study discontinuation?

CARGO will advance CRG-023, its tri-specific CAR T, into Phase 1 dose escalation study in Q2 2025, continue developing its allogeneic platform, and evaluate strategic options.

What was the safety profile of CRGX's firi-cel in the FIRCE-1 study?

18% of patients developed grade 3 or higher immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS), including grade 4 and 5 serious adverse events.