Studies highlight the range of targets and molecular approaches within the BMS multiple myeloma portfolio including bispecific T cell engager alnuctamab, first-in-class anti-BCMA CAR T cell therapy Abecma, GPRC5D CAR T (BMS-986393/CC-95266) and novel oral CELMoDTM agents mezigdomide and iberdomide
PRINCETON, NJ, USA I December 12, 2022 IBristol Myers Squibb (NYSE: BMY) today announced the first disclosure of results and presentation of new research from its multiple myeloma portfolio across targets and molecular approaches at the 64th American Society of Hematology (ASH) Annual Meeting and Exposition, underscoring the company’s commitment to raising standards to transform multiple myeloma outcomes for every patient.
“At ASH this year, we are highlighting the next wave of advances from our diverse multiple myeloma portfolio, reflecting our strategy of leveraging an array of approaches and targets against the disease,” said Samit Hirawat, M.D., executive vice president, chief medical officer, Global Drug Development, Bristol Myers Squibb. “Through continued partnership with the multiple myeloma community, we are working to push toward a reality in which every patient would have an opportunity to receive a tailored treatment option that offers the best possible outcomes.”
Results being presented at ASH highlight scientific progress across bispecific T cell engagers (TCE), chimeric antigen receptor (CAR) T cell therapies and novel CELMoDTM agents in advancing the treatment of relapsed/refractory multiple myeloma and include:
- First multicenter results from the Phase 1 study of bispecific TCE alnuctamab, administered subcutaneously every four weeks after six months, showing a reduction in inflammatory toxicity relative to intravenous administration, while maintaining anti-tumor activity with deep responses (Oral Presentation #162)
- First disclosure of Phase 1 results for GPRC5D CAR T (BMS-986393/CC-95266), demonstrating deep and durable responses with a manageable safety profile across all dose levels, including patients previously treated with a B-cell maturation antigen (BCMA)-directed CAR T cell therapy (Oral Presentation #364)
- Two first disclosures of results from cohorts 2a and 2c of the Phase 2 KarMMa-2 trial evaluating Abecma® (idecabtagene vicleucel), demonstrating durable responses and predictable safety in patients with multiple myeloma after early relapse or suboptimal response to stem cell transplant (Oral Presentation #361, Poster Presentation #3314)
- First results from the dose expansion cohort of the mezigdomide Phase 1/2 study evaluating the novel oral CELMoD agent with dexamethasone (DEX), showing durable efficacy and a manageable safety profile in patients who were highly refractory to multiple prior therapies (Oral Presentation #568)
- New results from a cohort with patients previously exposed to a BCMA-targeted therapy of the iberdomide Phase 1/2 study, evaluating the novel oral CELMoD agent with DEX, demonstrating clinically meaningful efficacy and safety regardless of type of prior anti-BCMA treatment (Poster Presentation #1918)
“Multiple myeloma continues to be an immensely challenging disease which affects patients across a number of demographics, fitness levels and comorbidities. While scientific advances have driven significant improvements in survival, the disease remains characterized by relapses and a disease burden that greatly impacts a patient’s quality of life,” said Brian Durie, M.D., chairman of the board of the International Myeloma Foundation. “These promising data at ASH represent important progress, and I am encouraged by the next wave of potential advances across a diverse range of targets and platforms, which may provide treating physicians with many options that can be tailored for unique patient needs.”
Alnuctamab (BMS-986349/CC-93269) Phase 1 Study Results
Alnuctamab is a bispecific T cell engager (TCE) that simultaneously binds myeloma cells expressing B-cell maturation antigen (BCMA) and T cells (via CD3) in a unique 2:1 fashion. This interaction aims to drive myeloma cell death by inducing T cell activation and release of proinflammatory cytokines and cytolytic enzymes.
In the ongoing alnuctamab CC-93269-MM-001 open-label, Phase 1 study, 138 patients with relapsed/refractory (R/R) multiple myeloma were enrolled (as of November 1, 2022) to receive escalating doses of alnuctamab administered either intravenously (IV) (n=70) or subcutaneously (SC) (n=68). Intravenous alnuctamab was administered as previously reported at target doses of 0.15–10 mg, with both fixed and step-up dosing, while SC alnuctamab was given to patients in two step-up doses (3 mg and 6 mg) followed by escalating target doses of 10, 15, 30, and 60 mg, given every one week for three months, then every two weeks for three months, followed by every four weeks after those six months.
In interim results, SC alnuctamab (n=68) showed an improved safety profile compared to IV delivery, with cytokine release syndrome (CRS) limited to low-grade, short-lived events, allowing for dose escalation to higher target doses. Intravenous and SC alnuctamab both exhibited promising pharmacodynamic effects, triggering the release of the hallmark cytokines of TCEs(e.g., IL-1 and IL-6). However, SC alnuctamab triggered reduced and delayed cytokine production compared to more potent CRS induced by IV delivery. Subcutaneous alnuctamab also demonstrated encouraging dose-dependent anti-tumor activity across all target doses, particularly in patients who received the 30 mg target dose.
| Alnuctamab CC-93269-MM-001 Study |
| Safety |
IV alnuctamab
(n=70) |
Cytokine Release Syndrome (CRS) – Any Grade |
76% (53/70) |
| Grade >3 CRS |
7% (5/70) |
SC alnuctamab
(n=68) |
CRS – Any Grade |
50% (34/68) |
| Grade >3 CRS |
0 |
| Median time to onset of CRS |
3 days (range: 1-20) |
| Median duration of CRS |
2 days (range: 1-11) |
SC alnuctamab efficacy
(n=68) |
| Overall response rate (ORR) |
53% (36/68) |
| ORR in patient treated with 30 mg dose |
65% (44/68) |
| Median duration of response (DOR) |
NR
(90% of responses ongoing at data cut-off) |
| Minimal residual disease (MRD)-negativity among patients who achieved a response (n=20 evaluable patients) |
80% (16/20) |
| |
|
|
|
GPRC5D CAR T (BMS-986393/CC-95266) Phase 1 Study Results
GPRC5D has been identified as an orphan receptor that is highly expressed on multiple myeloma cells, with limited expression in other tissues. BMS-986393 is a GPRC5D-directed autologous CAR T cell therapy.
This Phase 1, first-in-human, multicenter, open-label study is evaluating BMS-986393 in patients with R/R multiple myeloma who had received three or more prior lines of therapy. Prior BCMA-targeted treatment, including CAR T cell therapy, was allowed. Primary objectives of the study were to determine safety and tolerability of BMS-986393 and inform the recommended dose for future development.
At the time of the interim analysis, BMS-986393 demonstrated a well-tolerated safety profile with mostly low-grade and short-lived occurrences of CRS and neurotoxicity across all tested dose levels. Neurotoxicity was infrequent and low-grade, with no Grade 3 or 4 events reported, and events were reversible with steroid treatment. All on-target off-tumor adverse events were Grade 1, and the majority (78.6%) did not require treatment. Preliminary efficacy also supports the potential of BMS-986393 to elicit deep and durable responses.
| BMS-986393 Phase 1 Study |
Safety
(n=33) |
| CRS – Any Grade |
63.6% (21/33) |
| Grade 3/4 CRS |
6% (2/33) |
| Median time to onset CRS |
3 days (range: 1-9) |
| Median duration of CRS |
4 days |
| Neurotoxicity – Grade 1/2 |
6% (2/33) |
| Duration of neurotoxicity |
1-3 days |
| On-target off-tumor AEs – Grade 1 |
30% (10/33) |
| Dysgeusia/taste disorder |
15% (5/33) |
| Nail disorder |
9.1% (3/33) |
| Dysphagia |
3% (1/33) |
Efficacy
(n=19)
Median follow-up: 5.82 months |
| ORR |
89.5% (17/19) |
CRR
- CR – Patients treated with prior BCMA-directed CAR T cell therapies
- CR – Patients treated with prior BCMA-directed therapies
|
47.4% (9/19)
7 patients
2 patients |
| Patients treated with prior BCMA-directed therapies subgroup (n=9)
|
77.8% (7/9)
44.4% (4/9) |
| Patients remaining in follow-up |
78.9% (15/19) |
Abecma® (idecabtagene vicleucel) KarMMa Phase 2 Cohorts 2a and 2c Study Results
KarMMa-2 (NCT03601078) is a multi-cohort, open-label, multicenter Phase 2 trial evaluating Abecma in patients with relapsed and refractory multiple myeloma (Cohort 1), patients with multiple myeloma who have progressive disease within 18 months of initial treatment including autologous stem cell transplant (ASCT) (Cohort 2a), or in patients with inadequate response following ASCT during initial treatment (Cohort 2c). Based on results from Cohorts 2a and 2c, Abecma demonstrated complete and durable responses in a significant proportion of patients, alongside a well-established and predictable safety profile with mostly low-grade occurrences of CRS and neurotoxicity. Abecma is being jointly developed and commercialized in the U.S. as part of a Co-Development, Co-Promotion, and Profit Share Agreement between Bristol Myers Squibb and 2seventy bio.
Abecma KarMMa-2 Study COHORT 2a
(n=37)
Patients with multiple myeloma who had early relapse after frontline ASCT |
| Efficacy |
| CRR (primary efficacy endpoint) |
45.9%
(95% CI: 29.5-63.1) |
| ORR |
83.8%
(95% CI: 68-93.8) |
| Median DOR |
15.7 months
(95% CI: 7.6-19.8) |
| Safety |
| CRS – Grade 1/2 |
81.1% (30/37) |
| CRS – Grade 3 |
2.7% (1/37) |
| Neurotoxicity – Grade 1/2 |
21.6% (8/37) |
| *Median follow-up – 21.5 months |
COHORT 2c
(n=31)
Patients with newly diagnosed multiple myeloma who had an inadequate response to ASCT |
| Efficacy |
| CRR |
74.2%
(95% CI: 55.4-88.1) |
| ORR |
87.1%
(95% CI: 70.2-96.4) |
| Safety |
| CRS – Grade 1 |
45.2% (14/31) |
| CRS – Grade 2 |
12.9% (4/31) |
| Neurotoxicity |
6.5% (2/31)
Grade 1 – 1/31
Grade 3 – 1/31 |
| *Median follow-up – 27.9 months |
Novel CELMoD™ agents mezigdomide (CC-92480) and iberdomide (CC-220) Phase 1/2 Study Results
Cereblon E3 ligase modulators (CELMoD) are a class of oral immunomodulatory therapeutics that are designed to stimulate the immune system and directly kill cancer cells by inducing the degradation of tumor-promoting proteins. Bristol Myers Squibb is investigating two novel CELMoD agents, mezigdomide and iberdomide, for multiple myeloma that were intentionally designed to improve upon the demonstrated efficacy of the IMiD® agents, along with manageable tolerability, ease of administration, and the potential to improve patient outcomes. These agents co-opt cereblon to induce degradation of target proteins Ikaros and Aiolos, which inhibits tumor cell proliferation, promote tumor cell death, and induce immune-stimulatory effects.
The mezigdomide CC-92480-MM-001 trial is an ongoing open-label, international Phase 1/2 study to investigate the safety and efficacy of mezigdomide in combination with dexamethasone (DEX) in patients with relapsed/refractory (R/R) multiple myeloma. As part of the expansion cohort phase, 101 highly refractory patients that had received three or more prior lines of therapy, including an IMiD agent, a proteasome inhibitor (PI), and an anti-CD38 mAb, were given mezigdomide for 21 of 28 days in combination with weekly DEX at the recommended Phase 2 dose selected in part 1 of the study (1 mg once daily). The primary objective was efficacy as determined by objective response rate (ORR), while safety, tolerability and additional efficacy measures were included as the secondary objectives.
Based on interim results, mezigdomide, in combination with weekly DEX (40 mg; 20 mg if >75 years of age), showed promising efficacy in a highly refractory patient population. As of the data cut-off date, mezigdomide plus DEX showed a manageable safety profile.
| Mezigdomide CC-92489-MM-001 Study |
| Efficacy |
| ORR in patients receiving three or more prior lines of therapy |
40.6% (40/101)
(n=101) |
| ORR in patients that had also received prior BCMA-targeted therapies |
50% (15/30)
(n=30) |
| Safety |
| Grade 3/4 treatment-emergent adverse events (TEAEs) |
89.1% (90/101) |
Hematologic TEAEs
- Neutropenia
- Anemia
- Thrombocytopenia
|
76.2% (77/101) |
| Mezigdomide dose interruptions and reductions due to TEAEs |
29.7% (30/101) |
| Treatment discontinuation due to TEAEs |
5.9% (6/101) |
The iberdomide CC-220-MM-001 study is an ongoing Phase 1/2 multicenter, open-label and multi-cohort trial evaluating orally administered iberdomide in several combinations and segments of patients with R/R multiple myeloma. Results at ASH are being presented from the dose-expansion cohort evaluating iberdomide in combination with DEX in patients with multiple myeloma who have heavily-pretreated refractory disease and also received anti-BCMA therapy.
Iberdomide was given orally, 1.6 mg once daily for 21 of 28 days, plus weekly DEX (40 mg; 20 mg if >75 years of age). The primary objectives were preliminary efficacy measured by ORR and safety. Patients treated with iberdomide with DEX demonstrated meaningful clinical activity, regardless of modality (TCE, CAR T cell or antibody-drug conjugate therapy), suggesting that iberdomideretains its activity in these patients.
| Iberdomide CC-220-MM-001 Study |
Efficacy
(n=41) |
Overall response rate
*As of Sept. 6, 2022 |
34.1% (13/41)
|
| Safety |
Grade 3/4 treatment-emergent adverse events (TEAEs)
*Mostly hematologic, including leukopenia, anemia and thrombocytopenia |
80.5% (33/41) |
| Iberdomide dose interruptions and reductions due to TEAEs |
63.4% (26/41)
17.1% (7/41) |
| Treatment discontinuation due to TEAEs |
0 |
Please see full Prescribing Information, including Boxed WARNINGS and Medication Guide.
Bristol Myers Squibb: Transforming the Multiple Myeloma Treatment Paradigm
At BMS, we believe that every patient deserves a tailored treatment approach to achieve the best possible outcome for their disease, from extended survival and reduced treatment burden to the possibility of cure. Over two decades of trailblazing work in multiple myeloma, we have driven significant scientific and clinical advancements. As we look forward, we are leveraging our deep immunotherapy experience to progress an industry-leading pipeline across targets, molecular approaches and combinations (including BCMA-targeted therapies, targeted protein degradation, CAR T cell therapies and NK-cell engagers). Understanding that continued partnership with the multiple myeloma community is key to advancing scientific progress, we pride ourselves on an openness to collaborate, which is reflected in our ongoing research fueled by academic and industry partnerships. While multiple myeloma remains a relentless disease, we continue to transform the multiple myeloma treatment paradigm by dramatically improving outcomes for every patient.
Bristol Myers Squibb: Creating a Better Future for Cancer Patients
Bristol Myers Squibb is inspired by a single vision — transforming patients’ lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine, and through innovative digital platforms, are turning data into insights that sharpen their focus. Deep scientific expertise, cutting-edge capabilities and discovery platforms enable the company to look at cancer from every angle. Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. Because as a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future.
About Bristol Myers Squibb
Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram.
SOURCE: Bristol Myers Squibb
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Studies highlight the range of targets and molecular approaches within the BMS multiple myeloma portfolio including bispecific T cell engager alnuctamab, first-in-class anti-BCMA CAR T cell therapy Abecma, GPRC5D CAR T (BMS-986393/CC-95266) and novel oral CELMoDTM agents mezigdomide and iberdomide
PRINCETON, NJ, USA I December 12, 2022 IBristol Myers Squibb (NYSE: BMY) today announced the first disclosure of results and presentation of new research from its multiple myeloma portfolio across targets and molecular approaches at the 64th American Society of Hematology (ASH) Annual Meeting and Exposition, underscoring the company’s commitment to raising standards to transform multiple myeloma outcomes for every patient.
“At ASH this year, we are highlighting the next wave of advances from our diverse multiple myeloma portfolio, reflecting our strategy of leveraging an array of approaches and targets against the disease,” said Samit Hirawat, M.D., executive vice president, chief medical officer, Global Drug Development, Bristol Myers Squibb. “Through continued partnership with the multiple myeloma community, we are working to push toward a reality in which every patient would have an opportunity to receive a tailored treatment option that offers the best possible outcomes.”
Results being presented at ASH highlight scientific progress across bispecific T cell engagers (TCE), chimeric antigen receptor (CAR) T cell therapies and novel CELMoDTM agents in advancing the treatment of relapsed/refractory multiple myeloma and include:
- First multicenter results from the Phase 1 study of bispecific TCE alnuctamab, administered subcutaneously every four weeks after six months, showing a reduction in inflammatory toxicity relative to intravenous administration, while maintaining anti-tumor activity with deep responses (Oral Presentation #162)
- First disclosure of Phase 1 results for GPRC5D CAR T (BMS-986393/CC-95266), demonstrating deep and durable responses with a manageable safety profile across all dose levels, including patients previously treated with a B-cell maturation antigen (BCMA)-directed CAR T cell therapy (Oral Presentation #364)
- Two first disclosures of results from cohorts 2a and 2c of the Phase 2 KarMMa-2 trial evaluating Abecma® (idecabtagene vicleucel), demonstrating durable responses and predictable safety in patients with multiple myeloma after early relapse or suboptimal response to stem cell transplant (Oral Presentation #361, Poster Presentation #3314)
- First results from the dose expansion cohort of the mezigdomide Phase 1/2 study evaluating the novel oral CELMoD agent with dexamethasone (DEX), showing durable efficacy and a manageable safety profile in patients who were highly refractory to multiple prior therapies (Oral Presentation #568)
- New results from a cohort with patients previously exposed to a BCMA-targeted therapy of the iberdomide Phase 1/2 study, evaluating the novel oral CELMoD agent with DEX, demonstrating clinically meaningful efficacy and safety regardless of type of prior anti-BCMA treatment (Poster Presentation #1918)
“Multiple myeloma continues to be an immensely challenging disease which affects patients across a number of demographics, fitness levels and comorbidities. While scientific advances have driven significant improvements in survival, the disease remains characterized by relapses and a disease burden that greatly impacts a patient’s quality of life,” said Brian Durie, M.D., chairman of the board of the International Myeloma Foundation. “These promising data at ASH represent important progress, and I am encouraged by the next wave of potential advances across a diverse range of targets and platforms, which may provide treating physicians with many options that can be tailored for unique patient needs.”
Alnuctamab (BMS-986349/CC-93269) Phase 1 Study Results
Alnuctamab is a bispecific T cell engager (TCE) that simultaneously binds myeloma cells expressing B-cell maturation antigen (BCMA) and T cells (via CD3) in a unique 2:1 fashion. This interaction aims to drive myeloma cell death by inducing T cell activation and release of proinflammatory cytokines and cytolytic enzymes.
In the ongoing alnuctamab CC-93269-MM-001 open-label, Phase 1 study, 138 patients with relapsed/refractory (R/R) multiple myeloma were enrolled (as of November 1, 2022) to receive escalating doses of alnuctamab administered either intravenously (IV) (n=70) or subcutaneously (SC) (n=68). Intravenous alnuctamab was administered as previously reported at target doses of 0.15–10 mg, with both fixed and step-up dosing, while SC alnuctamab was given to patients in two step-up doses (3 mg and 6 mg) followed by escalating target doses of 10, 15, 30, and 60 mg, given every one week for three months, then every two weeks for three months, followed by every four weeks after those six months.
In interim results, SC alnuctamab (n=68) showed an improved safety profile compared to IV delivery, with cytokine release syndrome (CRS) limited to low-grade, short-lived events, allowing for dose escalation to higher target doses. Intravenous and SC alnuctamab both exhibited promising pharmacodynamic effects, triggering the release of the hallmark cytokines of TCEs(e.g., IL-1 and IL-6). However, SC alnuctamab triggered reduced and delayed cytokine production compared to more potent CRS induced by IV delivery. Subcutaneous alnuctamab also demonstrated encouraging dose-dependent anti-tumor activity across all target doses, particularly in patients who received the 30 mg target dose.
| Alnuctamab CC-93269-MM-001 Study |
| Safety |
IV alnuctamab
(n=70) |
Cytokine Release Syndrome (CRS) – Any Grade |
76% (53/70) |
| Grade >3 CRS |
7% (5/70) |
SC alnuctamab
(n=68) |
CRS – Any Grade |
50% (34/68) |
| Grade >3 CRS |
0 |
| Median time to onset of CRS |
3 days (range: 1-20) |
| Median duration of CRS |
2 days (range: 1-11) |
SC alnuctamab efficacy
(n=68) |
| Overall response rate (ORR) |
53% (36/68) |
| ORR in patient treated with 30 mg dose |
65% (44/68) |
| Median duration of response (DOR) |
NR
(90% of responses ongoing at data cut-off) |
| Minimal residual disease (MRD)-negativity among patients who achieved a response (n=20 evaluable patients) |
80% (16/20) |
| |
|
|
|
GPRC5D CAR T (BMS-986393/CC-95266) Phase 1 Study Results
GPRC5D has been identified as an orphan receptor that is highly expressed on multiple myeloma cells, with limited expression in other tissues. BMS-986393 is a GPRC5D-directed autologous CAR T cell therapy.
This Phase 1, first-in-human, multicenter, open-label study is evaluating BMS-986393 in patients with R/R multiple myeloma who had received three or more prior lines of therapy. Prior BCMA-targeted treatment, including CAR T cell therapy, was allowed. Primary objectives of the study were to determine safety and tolerability of BMS-986393 and inform the recommended dose for future development.
At the time of the interim analysis, BMS-986393 demonstrated a well-tolerated safety profile with mostly low-grade and short-lived occurrences of CRS and neurotoxicity across all tested dose levels. Neurotoxicity was infrequent and low-grade, with no Grade 3 or 4 events reported, and events were reversible with steroid treatment. All on-target off-tumor adverse events were Grade 1, and the majority (78.6%) did not require treatment. Preliminary efficacy also supports the potential of BMS-986393 to elicit deep and durable responses.
| BMS-986393 Phase 1 Study |
Safety
(n=33) |
| CRS – Any Grade |
63.6% (21/33) |
| Grade 3/4 CRS |
6% (2/33) |
| Median time to onset CRS |
3 days (range: 1-9) |
| Median duration of CRS |
4 days |
| Neurotoxicity – Grade 1/2 |
6% (2/33) |
| Duration of neurotoxicity |
1-3 days |
| On-target off-tumor AEs – Grade 1 |
30% (10/33) |
| Dysgeusia/taste disorder |
15% (5/33) |
| Nail disorder |
9.1% (3/33) |
| Dysphagia |
3% (1/33) |
Efficacy
(n=19)
Median follow-up: 5.82 months |
| ORR |
89.5% (17/19) |
CRR
- CR – Patients treated with prior BCMA-directed CAR T cell therapies
- CR – Patients treated with prior BCMA-directed therapies
|
47.4% (9/19)
7 patients
2 patients |
| Patients treated with prior BCMA-directed therapies subgroup (n=9)
|
77.8% (7/9)
44.4% (4/9) |
| Patients remaining in follow-up |
78.9% (15/19) |
Abecma® (idecabtagene vicleucel) KarMMa Phase 2 Cohorts 2a and 2c Study Results
KarMMa-2 (NCT03601078) is a multi-cohort, open-label, multicenter Phase 2 trial evaluating Abecma in patients with relapsed and refractory multiple myeloma (Cohort 1), patients with multiple myeloma who have progressive disease within 18 months of initial treatment including autologous stem cell transplant (ASCT) (Cohort 2a), or in patients with inadequate response following ASCT during initial treatment (Cohort 2c). Based on results from Cohorts 2a and 2c, Abecma demonstrated complete and durable responses in a significant proportion of patients, alongside a well-established and predictable safety profile with mostly low-grade occurrences of CRS and neurotoxicity. Abecma is being jointly developed and commercialized in the U.S. as part of a Co-Development, Co-Promotion, and Profit Share Agreement between Bristol Myers Squibb and 2seventy bio.
Abecma KarMMa-2 Study COHORT 2a
(n=37)
Patients with multiple myeloma who had early relapse after frontline ASCT |
| Efficacy |
| CRR (primary efficacy endpoint) |
45.9%
(95% CI: 29.5-63.1) |
| ORR |
83.8%
(95% CI: 68-93.8) |
| Median DOR |
15.7 months
(95% CI: 7.6-19.8) |
| Safety |
| CRS – Grade 1/2 |
81.1% (30/37) |
| CRS – Grade 3 |
2.7% (1/37) |
| Neurotoxicity – Grade 1/2 |
21.6% (8/37) |
| *Median follow-up – 21.5 months |
COHORT 2c
(n=31)
Patients with newly diagnosed multiple myeloma who had an inadequate response to ASCT |
| Efficacy |
| CRR |
74.2%
(95% CI: 55.4-88.1) |
| ORR |
87.1%
(95% CI: 70.2-96.4) |
| Safety |
| CRS – Grade 1 |
45.2% (14/31) |
| CRS – Grade 2 |
12.9% (4/31) |
| Neurotoxicity |
6.5% (2/31)
Grade 1 – 1/31
Grade 3 – 1/31 |
| *Median follow-up – 27.9 months |
Novel CELMoD™ agents mezigdomide (CC-92480) and iberdomide (CC-220) Phase 1/2 Study Results
Cereblon E3 ligase modulators (CELMoD) are a class of oral immunomodulatory therapeutics that are designed to stimulate the immune system and directly kill cancer cells by inducing the degradation of tumor-promoting proteins. Bristol Myers Squibb is investigating two novel CELMoD agents, mezigdomide and iberdomide, for multiple myeloma that were intentionally designed to improve upon the demonstrated efficacy of the IMiD® agents, along with manageable tolerability, ease of administration, and the potential to improve patient outcomes. These agents co-opt cereblon to induce degradation of target proteins Ikaros and Aiolos, which inhibits tumor cell proliferation, promote tumor cell death, and induce immune-stimulatory effects.
The mezigdomide CC-92480-MM-001 trial is an ongoing open-label, international Phase 1/2 study to investigate the safety and efficacy of mezigdomide in combination with dexamethasone (DEX) in patients with relapsed/refractory (R/R) multiple myeloma. As part of the expansion cohort phase, 101 highly refractory patients that had received three or more prior lines of therapy, including an IMiD agent, a proteasome inhibitor (PI), and an anti-CD38 mAb, were given mezigdomide for 21 of 28 days in combination with weekly DEX at the recommended Phase 2 dose selected in part 1 of the study (1 mg once daily). The primary objective was efficacy as determined by objective response rate (ORR), while safety, tolerability and additional efficacy measures were included as the secondary objectives.
Based on interim results, mezigdomide, in combination with weekly DEX (40 mg; 20 mg if >75 years of age), showed promising efficacy in a highly refractory patient population. As of the data cut-off date, mezigdomide plus DEX showed a manageable safety profile.
| Mezigdomide CC-92489-MM-001 Study |
| Efficacy |
| ORR in patients receiving three or more prior lines of therapy |
40.6% (40/101)
(n=101) |
| ORR in patients that had also received prior BCMA-targeted therapies |
50% (15/30)
(n=30) |
| Safety |
| Grade 3/4 treatment-emergent adverse events (TEAEs) |
89.1% (90/101) |
Hematologic TEAEs
- Neutropenia
- Anemia
- Thrombocytopenia
|
76.2% (77/101) |
| Mezigdomide dose interruptions and reductions due to TEAEs |
29.7% (30/101) |
| Treatment discontinuation due to TEAEs |
5.9% (6/101) |
The iberdomide CC-220-MM-001 study is an ongoing Phase 1/2 multicenter, open-label and multi-cohort trial evaluating orally administered iberdomide in several combinations and segments of patients with R/R multiple myeloma. Results at ASH are being presented from the dose-expansion cohort evaluating iberdomide in combination with DEX in patients with multiple myeloma who have heavily-pretreated refractory disease and also received anti-BCMA therapy.
Iberdomide was given orally, 1.6 mg once daily for 21 of 28 days, plus weekly DEX (40 mg; 20 mg if >75 years of age). The primary objectives were preliminary efficacy measured by ORR and safety. Patients treated with iberdomide with DEX demonstrated meaningful clinical activity, regardless of modality (TCE, CAR T cell or antibody-drug conjugate therapy), suggesting that iberdomideretains its activity in these patients.
| Iberdomide CC-220-MM-001 Study |
Efficacy
(n=41) |
Overall response rate
*As of Sept. 6, 2022 |
34.1% (13/41)
|
| Safety |
Grade 3/4 treatment-emergent adverse events (TEAEs)
*Mostly hematologic, including leukopenia, anemia and thrombocytopenia |
80.5% (33/41) |
| Iberdomide dose interruptions and reductions due to TEAEs |
63.4% (26/41)
17.1% (7/41) |
| Treatment discontinuation due to TEAEs |
0 |
Please see full Prescribing Information, including Boxed WARNINGS and Medication Guide.
Bristol Myers Squibb: Transforming the Multiple Myeloma Treatment Paradigm
At BMS, we believe that every patient deserves a tailored treatment approach to achieve the best possible outcome for their disease, from extended survival and reduced treatment burden to the possibility of cure. Over two decades of trailblazing work in multiple myeloma, we have driven significant scientific and clinical advancements. As we look forward, we are leveraging our deep immunotherapy experience to progress an industry-leading pipeline across targets, molecular approaches and combinations (including BCMA-targeted therapies, targeted protein degradation, CAR T cell therapies and NK-cell engagers). Understanding that continued partnership with the multiple myeloma community is key to advancing scientific progress, we pride ourselves on an openness to collaborate, which is reflected in our ongoing research fueled by academic and industry partnerships. While multiple myeloma remains a relentless disease, we continue to transform the multiple myeloma treatment paradigm by dramatically improving outcomes for every patient.
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About Bristol Myers Squibb
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