/
/
Multiple Myeloma Bispecific Antibody Talquetamab Update
Multiple Myeloma Bispecific Antibody Talquetamab Update image
Multiple Myeloma Bispecific Antibody Talquetamab Update
Posted Jun 23, 2022

Johnson and Johnson/Janssen (JNJ) is almost overwhelming us, myeloma patients, with results from a substantive number of human trials in myeloma patients.

Over the past week we have seen data from five studies of teclistamab (recently discussed here), long-term follow-up results of their CAR-T product Carvykti and now we can add early results of their novel treatment talquetamab. All of this builds on their success with both Darzalex and Darzalex Faspro.

Talquetamab is a ‘first in class’ bispecific antibody that targets the GPRC5D, a new target expressed on myeloma cells, and CD3, a protein expressed on T-cells. GPRC5D has limited expression on healthy human tissue but is highly expressed on malignant myeloma cells.

This construct brings the killing T-cell in contact with the cancerous cell. JNJ has presented Phase I data with both mono treatment with talquetamab and combination treatment with talquetamab + Darzalex Faspro. Please remember that a Phase I study evaluates safety, preliminary efficacy as well as recommended Phase II dosing (RP2D) for follow-on human studies to support the registration dossiers with regulatory agencies in the future.

Talquetamab as monotherapy

Two dosing levels were identified: 405 and 800 micrograms/kg (μg/kg body weight). Patients were stepped-up gradually to the target dose in order to mitigate severe cytokine release syndrome (CRS) and required pre-medications were administered during this step-up period.

Nearly all of the patients had been triple class exposed  prior to relapse, about 75 percent. Results from these sub-programs can be summarized as follows:

 

405 μg/kg

(30 patients)

800 μg/kg

(44 patients)

Patient characteristics

 

 

Triple class exposed

Triple class refractory

Penta drug exposed

Penta drug refractory

Prior BCMA directed treatment

100%

77%

80%

20%

30%

98%

77%

68 %

27%

27%

Overall Response Rate (ORR)    

All patients

Triple class refractory

Penta class refractory

70%

65%

83%

64%

68%

75%

Median Follow-Up Time

13.2 months

7.7 months

Patients with a Response    

Very good partial response or better (VGPR)

Complete response or better (CR)

Stringent complete response (sCR)

57 %

7 %

23 %

57 %

11 %

9 %

Median Duration of Response 10.2 months 13 months
Most Common Adverse Events 77% 79%

Cytokine release syndrome (CRS)

Neutropenia

Skin-related adverse events

Loss of taste

Infections

67 %

67 %

63 %

47 %

Not reported

73 %

57 %

39 %

 

Combo treatment talquetamab + Darzalex Faspro

A total of 58 patients were treated (14 with a talquetamab dose of 405 μg/kg and 44 with a dose of 800 μg/kg). Darzalex Faspro was dosed at the approved dosing level. Results can be summarized as follows:

 

405 μg

(14 patients)

800 μg

(44 patients)

Patient characteristics

Triple class exposed

Prior exposure to anti-CD38 antibody

Prior BCMA directed treatment

100 %

77 %

72 %

Median follow-up time

5.1 months

ORR for all patients

Patients with a response showed :

Very good partial response or better (VGPR)

Complete response or better (CR)

Stringent complete response (sCR)

Median duration of response

80 %

 

63 %

29 %

Not reported

Not yet reported

Most common adverse events

Cytokine release syndrome (CRS)

Dry Mouth

Anemia

Skin-related adverse events and nail disorders

Loss of taste

Infections

 

71 %

71 %

 

 

71 %

 

77 %

 

43 %

81 %

59%

53 %

 

The loss of taste/altered sense of taste was managed with managed with supportive care and, if needed, dose adjustments.” The “supportive care” was not explained as to what that entailed, though I’d say that more than a few of us would be interested in that. Please note that the patients enrolled in these two studies can be labeled as very sick.

The company and its researchers conclude that, “Results from the study show heavily pretreated patients with multiple myeloma treated with the combination, including talquetamab at the recommended subcutaneous Phase 2 dose (RP2D) administered weekly (QW) or every two weeks (Q2W), achieved high rates of responses, including for patients refractory to anti-CD38 treatment.”

Chances are quite good that we may be looking here at another future treatment option when our disease progresses, assuming, of course, that the continuation of these studies will build upon the successful outcomes of these early results and that no unforeseen regulatory obstacles will occur. It makes sense that FDA will use its best efforts to expedite the future approval of talquetamab considering that it is a truly novel “first in class” compound. That being said, we will still be several years away before we will see this addition to myeloma treatment in clinical practice, though every added treatment option provides added hope for us.

The author Paul Kleutghen

about the author
Paul Kleutghen

I am a patient diagnosed in 2014 with primary plasma cell leukemia (pPCL), a rare and aggressive variant of multiple myeloma and have been very fortunate to find successful treatment at the division of Cellular Therapy at the Duke University Cancer Institute. My wife, Vicki, and I have two adult children and two grandsons who are the ‘lights of our lives’. Successful treatment has allowed Vicki and I to do what we love best : traveling the world, albeit it with some extra precautions to keep infections away. My career in the pharmaceutical industry has given me insights that I am currently putting to use as an advocate to lower drug pricing, especially prices for anti-cancer drugs. I am a firm believer that staying mentally active, physically fit, compliant to our treatment regimen and taking an active interest in our disease are keys to successful treatment outcomes.

More Myeloma News Articles

Get the latest thought leadership on Myeloma delivered straight to your inbox.

Subscribe to the weekly "HealthTree Community for Myeloma Newsletter" for Myeloma news, life with Myeloma stories, Myeloma clinical trials, Myeloma 101 articles and events with Myeloma experts.

Thanks to our HealthTree Community for Myeloma Sponsors:

Genentech
Abbvie
Bristol Myers Squibb
Janssen Oncology
GSK

Follow Us

facebook instagram twitter youtube

Copyright © 2022 HealthTree Foundation. All Rights Reserved.

The HealthTree Foundation / Myeloma Crowd is a qualified 501(c)(3) tax-exempt organization. Tax ID 45-5354811

 https://www.guidestar.org/profile/45-5354811