Elranatamab

Investigators in China report that a single intravenous infusion of ESO-T01, a nanobody-directed lentiviral vector linked to AstraZeneca, generated functional anti-BCMA CAR-T cells directly inside patients with relapsed or refractory multiple myeloma, bypassing the need for ex vivo cell manufacturing, according to a Phase I study published in Nature Medicine. The in vivo CAR-T approach produced objective responses in four of five treated patients, including three stringent complete remissions, without lymphodepleting chemotherapy or leukapheresis. The ESO-T01 clinical trial (NCT06791681), conducted at sites including Tongji Hospital and Union Hospital in Wuhan, enrolled five consecutively treated male patients with a median of three prior lines of therapy. A second Phase I study (NCT06691685) is also recruiting at Union Hospital. Full author affiliations and the corporate sponsor were not disclosed in the available abstract, though the proprietary product designation suggests involvement of a biotechnology company responsible for the vector’s development. Single infusion replaces weeks of manufacturing The study tested ESO-T01 at a dose of 0.2 × 10⁹ transduction units delivered as a single intravenous infusion. The vector is an immune-shielded lentiviral particle engineered with surface nanobodies that redirect its tropism to circulating T cells. Upon binding, the vector delivers a humanized anti-BCMA chimeric antigen receptor transgene that integrates into the T cell genome, converting the patient’s own T cells into CAR-T cells without removing them from the body. This approach eliminates three steps that define conventional CAR-T cell generation: leukapheresis to collect patient T cells, weeks-long ex vivo manufacturing at centralized facilities, and lymphodepleting chemotherapy conditioning prior to reinfusion. In the current study, patients received ESO-T01 without any of these interventions. CAR-positive T cells were detectable in peripheral blood as early as day 7 post-infusion, with peak expansion around days 10 to 14. Both CD4-positive and CD8-positive CAR-T cell populations were generated. The cells persisted throughout the follow-up period, which extended to approximately six months. Responses deepened over time in pretreated population Four of five patients achieved objective responses. Three reached stringent complete remission and one achieved very good partial response. Responses deepened over time, with patients progressing sequentially from partial response to deeper remission categories. All four evaluable responders achieved minimal residual disease negativity at a sensitivity threshold of 10⁻⁵ by day 60, and all maintained that status at last follow-up. Soluble BCMA levels declined to the normal range in responders, consistent with elimination of malignant plasma cells. One patient died before the first efficacy assessment due to spinal cord compression from progressive extramedullary myeloma. The investigators attributed this event to underlying disease rather than to ESO-T01. At a median follow-up of 6.0 months, all responses remained ongoing. No formal statistical comparisons were performed given the sample size of five patients. Safety profile No dose-limiting toxicities occurred at the tested dose. Cytokine release syndrome developed in four of five patients, but all events were grade 1 or grade 2 and were managed with standard supportive care, including tocilizumab in some cases. No immune effector cell-associated neurotoxicity syndrome was observed in any patient, a finding that contrasts with the approximately 10 to 20 percent incidence reported with approved ex vivo anti-BCMA CAR-T products such as idecabtagene vicleucel and ciltacabtagene autolcel. No severe or unexpected infections were reported. The absence of lymphodepleting chemotherapy in the treatment protocol preserved baseline immune function, which may have contributed to the infection profile. The investigators reported no evidence of insertional oncogenesis or off-target transduction of non-T cell lineages. The in vivo CAR-T landscape ESO-T01 was discovered by Belgium-based EsoBiotec and acquired by AstraZeneca in a March 2025 deal worth up to USD 1 billion. Multiple companies are pursuing in vivo CAR-T therapy through different delivery platforms. Umoja Biopharma has initiated a Phase I trial of UB-VV100, a lentiviral-based in vivo CAR-T targeting CD19 for B-cell malignancies. Capstan Therapeutics, acquired by Roche in 2024, is developing lipid nanoparticle-based mRNA delivery to T cells, an approach that produces transient rather than stable CAR expression. Kelonia Therapeutics, Orna Therapeutics, and Interius BioTherapeutics are pursuing related platforms at the preclinical stage. The approved multiple myeloma treatment landscape already includes two ex vivo anti-BCMA CAR-T products — idecabtagene vicleucel from BMS/2seventy bio and ciltacabtagene autolcel from Janssen/Legend Biotech — along with BCMA-targeting bispecific antibodies teclistamab and elranatamab. Bispecific antibodies are off-the-shelf and address the same accessibility problem that in vivo approaches aim to solve, but they require continuous dosing and have not demonstrated the depth of remission associated with CAR-T therapy. Several allogeneic CAR-T programs targeting BCMA, including Caribou Biosciences’ CB-011 and programs from Allogene Therapeutics and Poseida Therapeutics, are also in early clinical development. Your email address will not be published. Required fields are marked * Comment * Name * Email * Website

Novel Combination Regimen Positions Cemsidomide for Use in Earlier Lines of Therapy WATERTOWN, Mass., March 25, 2026 (GLOBE NEWSWIRE) -- C4 Therapeutics, Inc. (C4T) (Nasdaq: CCCC), a clinical-stage biopharmaceutical company dedicated to advancing targeted protein degradation science, today announced that the first patient has been dosed with cemsidomide, an oral IKZF1/3 degrader, in a Phase 1b trial evaluating cemsidomide and dexamethasone in combination with elranatamab (ELREXFIO ® ), an FDA-approved B-cell maturation antigen CD3 targeted bispecific antibody, for the treatment of relapsed/refractory multiple myeloma (RRMM). “Data from our Phase 1 trial support cemsidomide as a potential best-in-class, next-generation IKZF1/3 degrader and the initiation of this Phase 1b trial, along with our late-line Phase 2 MOMENTUM trial, enable an efficient path toward bringing cemsidomide to growing myeloma patient populations across multiple lines of therapy,” said Len Reyno, M.D., chief medical officer of C4 Therapeutics. “Bispecific T-cell engagers have quickly become a critical treatment pillar in multiple myeloma while IKZF1/3 degraders remain foundational therapies across multiple lines and combination regimens in multiple myeloma. In this combination with elranatamab, we see an opportunity to leverage cemsidomide’s potent direct anti-myeloma effect and its ability to enhance the immune environment which has the potential to deliver a deeper and more durable therapeutic response for patients, including those in earlier lines of therapy.” The Phase 1b trial is an open-label, multicenter study to establish an optimal dose for cemsidomide in combination with elranatamab by evaluating the safety and tolerability as well as preliminary anti-myeloma activity of cemsidomide in combination with elranatamab in RRMM patients. The trial will enroll up to 54 patients to evaluate cemsidomide in combination with elranatamab, beginning at the 75 µg dose of cemsidomide with the opportunity to explore 50 µg and 100 µg doses of cemsidomide. The primary endpoint is to assess the safety and tolerability of cemsidomide in combination with elranatamab. Secondary endpoints will evaluate anti-myeloma activity per the International Myeloma Working Group (IMWG) response criteria, which will include the overall response rate, minimal-residual disease (MRD)-negative complete response rate, duration of response and other relevant measures. In October 2025, C4T and Pfizer entered into a clinical trial collaboration supply agreement under which Pfizer provides elranatamab at no cost while C4T sponsors and conducts the clinical trial. Phase 1b data from all cohorts evaluating cemsidomide in combination with elranatamab is anticipated in mid-2027. The Phase 1b trial is part of a broader developmental strategy to support cemsidomide’s use across multiple lines of treatment. This strategy also includes the ongoing Phase 2 MOMENTUM Trial investigating the use of cemsidomide and dexamethasone in the fourth line of treatment or later. In addition to these two trials, C4T intends to evaluate cemsidomide in combination with other anti-myeloma agents, and remains on track to share these plans in mid-2026. About Cemsidomide Cemsidomide is an investigational, orally bioavailable molecular glue degrader (MonoDAC ® degrader) of IKZF1/3, transcription factors foundational to multiple myeloma biology. Data from the Phase 1 trial, which has completed enrollment, show cemsidomide’s differentiated safety and tolerability pro potentially class-leading anti-myeloma activity that support the potential for durable outcomes. About Cemsidomide in Combination with Elranatamab (ELREXFIO ® ) The Phase 1b trial is designed to evaluate the safety, tolerability and preliminary efficacy of cemsidomide and dexamethasone in combination with elranatamab, an FDA-approved B-cell maturation antigen CD3 targeted bispecific antibody. Data generated from the cemsidomide Phase 1 trial in relapsed/refractory multiple myeloma demonstrate robust T-cell activation and cytokine expression across multiple doses. By activating immune T-cells, cemsidomide, when combined with a BCMAxCD3 bispecific such as elranatamab, may amplify the anti-myeloma immune response and lead to deeper and more durable responses. The study will evaluate different cemsidomide dose levels (beginning with 75 µg, with the opportunity to simultaneously explore 50 µg and 100 µg) in patients who have received one to four prior lines of therapy, which must have consisted of at least one IKZF1/3 degrader. Exclusion criteria for patients include those who have received prior treatment with a BCMA-directed T-cell engager or BCMA-directed CAR-T therapy. More information is available at clinicaltrials.gov (NCT07280013). About the MOMENTUM Trial MOMENTUM (Multi-center trial Of cemsidoMidE iN relapsed/refracTory mUltiple Myeloma) is a Phase 2, open-label, single-arm, study to evaluate efficacy, safety, pharmacokinetics and pharmacodynamics of cemsidomide in combination with dexamethasone in patients with relapsed/refractory multiple myeloma. Data from the Phase 1 trial identified 100 µg as the recommended Phase 2 dose. The primary endpoint is overall response rate per International Myeloma Working Group response criteria, as assessed by an independent review committee. Approximately 100 patients who have received at least three prior anti-myeloma regimens that must have included an IKZF1/3 degrader, a proteasome inhibitor, an anti-CD38 antibody, and a T-cell engager or CAR-T therapy will be enrolled in the trial. More information is available at clinicaltrials.gov (NCT07284758). About Multiple Myeloma Multiple myeloma (MM) is a rare blood cancer affecting plasma cells. Approximately 36,000 people in the United States are diagnosed with MM each year. Approved IKZF1/3 degraders remain foundational therapies across lines of MM treatment. Despite advances, including immune-directed approaches, most patients ultimately relapse, underscoring a growing need for new therapeutics options that continue to leverage IKZF1/3 degradation to drive myeloma cell death and T-cell activation. About C4 Therapeutics C4 Therapeutics (C4T) (Nasdaq: CCCC) is a clinical-stage biopharmaceutical company dedicated to delivering on the promise of targeted protein degradation science to create a new generation of medicines that transforms patients’ lives. C4T is progressing targeted oncology programs through clinical studies and leveraging its TORPEDO ® platform to efficiently design and optimize small-molecule medicines to address difficult-to-treat diseases. C4T’s degrader medicines are designed to harness the body’s natural protein recycling system to rapidly degrade disease-causing proteins, offering the potential to overcome drug resistance, drug undruggable targets and improve patient outcomes. For more information, please visit . Forward Looking Statements This press release contains “forward-looking statements” of C4 Therapeutics, Inc. within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements may include, but may not be limited to, express or implied statements regarding our ability to develop potential therapies for patients; the design and potential efficacy of our therapeutic approaches; the predictive capability of our TORPEDO ® platform in the development of novel, selective, orally bioavailable BiDAC™ and MonoDAC ® degraders; the potential timing, design and advancement of our preclinical studies and clinical trials, including the potential timing for and receipt of regulatory authorization related to clinical trials and other clinical development activities including clinical trial commencement and patient enrollment; our ability and the potential to successfully manufacture and supply our product candidates for clinical trials; our ability to replicate results achieved in our preclinical studies or clinical trials in any future studies or trials; our ability to replicate interim or early-stage results from our clinical trials in the results obtained when those clinical trials are completed or when those therapies complete later-stage clinical trials; regulatory developments in the United States and foreign countries; the anticipated timing and content of presentations of data from our clinical trials; and our ability to fund our future operations. Any forward-looking statements in this press release are based on management’s current expectations and beliefs of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: uncertainties related to the initiation, timing, advancement and conduct of preclinical and clinical studies and other development requirements for our product candidates; the risk that any one or more of our product candidates will cost more to develop or may not be successfully developed and commercialized; and the risk that sufficient capital to fund our future operations will be available to us on acceptable terms or at the times required. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled “Risk Factors” in C4 Therapeutics’ most recent Annual Report on Form 10-K and/or Quarterly Report on Form 10-Q, as filed with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and C4 Therapeutics undertakes no duty to update this information unless required by law. Contacts: Investors: Courtney Solberg Associate Director, Investor Relations CSolberg@c4therapeutics.com Media: Loraine Spreen Senior Director, Corporate Communications & Patient Advocacy LSpreen@c4therapeutics.com