A Multicenter, Randomized, Double-Blind, Active Comparator-Controlled, Adaptive Phase 2/3 Study to Evaluate the Safety and Efficacy of EIK1001 and Pembrolizumab Versus Placebo and Pembrolizumab as First-Line Therapy in Participants With Advanced Melanoma (TeLuRide-006)

More details:

Mechanism of Action

EIK1001, also known as BDB001, is a first-in-class Toll-like receptor 7 and 8 (TLR7/8) agonist administered intravenously. It activates both plasmacytoid and myeloid dendritic cells, initiating innate and adaptive immune responses against cancer cells. This systemic delivery allows for broader treatment of solid tumors compared to intratumoral TLR agonists. (businesswire.com)

Efficacy

Monotherapy

In a Phase 1 trial involving 36 patients with advanced solid tumors, EIK1001 demonstrated a disease control rate of 62%, with 6% achieving durable partial responses. Notably, responses were observed in renal cell carcinoma and non-small cell lung cancer, including tumors refractory to prior anti-PD-(L)1 therapies. (businesswire.com)

Combination with Pembrolizumab

A Phase 1 study evaluated EIK1001 combined with pembrolizumab in 51 patients with advanced solid tumors. The combination yielded an overall response rate of 14%, including 3 complete responses and 4 partial responses. Disease control was achieved in 48% of patients, with a median duration of response of 10 months. Responses were noted even in heavily pretreated patients and those with low or negative PD-L1 tumor expression. (ascopubs.org)

Combination with Atezolizumab

In another Phase 1 trial, 41 patients received EIK1001 with atezolizumab. The combination resulted in an 8.1% overall response rate, with disease control observed in 51.4% of patients. The median duration of response was 13 months. Notably, responses occurred in patients with prior anti-PD-1 therapy and those with PD-L1 negative tumors. (ascopubs.org)

Safety

EIK1001 has been generally well-tolerated across studies:

• Monotherapy: Most adverse events (AEs) were Grade 1 or 2. Grade 3 AEs occurred in 8.3% of patients, including cytokine release syndrome (CRS), which resolved within 2 to 5 days. No Grade 4 or 5 AEs were reported. Common AEs included chills, fever, fatigue, nausea, and pruritus. (businesswire.com)

• Combination with Pembrolizumab: Treatment-related AEs were reported in 82.4% of patients, with 17.7% experiencing Grade 3 or higher AEs. Manageable CRS occurred in 9.8% of patients, leading to one discontinuation. No treatment-related deaths were reported. (ascopubs.org)

• Combination with Atezolizumab: Treatment-related AEs were observed in 68.3% of patients, with 9.8% experiencing Grade 3 or higher AEs. CRS was reported in 2.4% of patients. No treatment-related deaths occurred. (ascopubs.org)

Further Reading

• Seven and Eight Biopharma Presents Promising Interim Phase 1 Results for BDB001 at The Society for Immunotherapy of Cancer (SITC) 35th Anniversary Annual Meeting

• Seven and Eight Biopharma’s BDB001 in Combination with Pembrolizumab Shows Favorable Safety and Clinical Responses in Interim Phase 1 Data Presented at the 2021 ASCO Annual Meeting

• Seven and Eight Biopharma’s BDB001 in Combination with an anti-PD-L1 mAb Shows Favorable Safety and Clinical Responses in Interim Phase 1 Data Presented at the 2021 SITC Annual Meeting

• Safety and preliminary efficacy of EIK1001 in combination with pembrolizumab in participants with advanced solid tumors.

• Safety and preliminary efficacy of EIK1001 in combination with atezolizumab in participants with advanced solid tumors.

Last updated: Apr 2025

Inclusion Criteria:

To be eligible for inclusion in this study, participants must:

* Be ≥ 18 years of age on the day of signing of informed consent.

* Have a life expectancy of at least 3 months.

* Have histologically or cytologically confirmed Stage 3 (unresectable) or Stage 4 metastatic melanoma per AJCC 8th ed. and be eligible for standard therapy with pembrolizumab.

* Have at least 1 lesion with measurable disease at Baseline by CT or MRI according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by assessment of local site Investigator/radiologist.

* Have known BRAF V600 mutation status or consent to BRAF V600 mutation testing per local institutional standards during the screening period

* Have completed prior radiotherapy at least 2 weeks prior to study treatment administration.

* Have an ECOG Performance Status of 0 to 1.

* Have adequate organ and marrow function as defined by normal CBC, coagulation, serum chemistry and liver function tests on specimens collected within 10 days of treatment start.

* Have a negative serum pregnancy test within 72 hours prior to receiving the first dose of study medication (applies to women of childbearing potential \[WOCBP\]).

* Be willing to use either 2 adequate methods of contraception, 1 adequate method plus a hormonal method of contraception, or be willing to abstain from heterosexual activity throughout the study (Visit 1 to 120 days after the last dose of study therapy; applies to WOCBP who are not menopausal for \> 2 years, post-hysterectomy/oophorectomy, or surgically sterilized).

* Agree to use an approved adequate contraceptive method throughout the study (Visit 1 to 120 days after the last dose of study therapy; applies to sexually active male participants with a partner who is WOCBP).

* Be willing and able to provide written, informed consent for the study.

Exclusion Criteria:

A participant is excluded from the study if any of the following criteria apply:

* Has melanoma of ocular origin.

* Is currently enrolled in or has recently participated in a study of an IMP and received an IMP within 4 weeks or 5 half-lives (whichever is shorter) of administration of EIK1001 or placebo.

* Prior to the 1St dose of EIK1001 or placebo, the prospective participant has received systemic therapy for advanced melanoma.

* Note: prior adjuvant or neoadjuvant melanoma therapies (such as anti-PD-1 or anti CTLA 4 therapies or BRAF/MEK inhibitors) are permitted if all related AEs have either returned to Baseline or stabilized, with a minimum of 6 months between the last dose of prior therapy and documented disease progression.

* Experienced a ≥ Grade 3 AE while receiving prior anti PD 1 therapy.

* Has had major surgery (\< 3 weeks prior to the first dose).

* Has received a live-virus vaccination within 30 days of the first dose of study treatment.

* Has a known history of prior malignancy, unless the participant has undergone potentially curative therapy with no evidence of disease recurrence for 5 years.

* Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate if they are clinically stable for at least 4 weeks with no evidence of new or enlarging brain metastases. There must be no need for immunosuppressive doses of glucocorticoids for at least 2 weeks prior to study treatment administration.

* There is a mean resting QTcF \> 470 ms on triplicate electrocardiograms.

* There is active autoimmune disease that has required systemic treatment in the past 2 years. The following autoimmune conditions are permitted: Type 1 diabetes, hypothyroidism (on hormone replacement), or- vitiligo, psoriasis and alopecia as long as no systemic treatment is required.

* There is either chronic treatment with systemic steroids, other immunosuppressive medication, or either of these has been administered within 14 days of start of study treatment.

* Note: Participants with asthma that require intermittent use of bronchodilators, inhaled steroids, or local steroid injections are eligible. Steroid replacement for adrenal insufficiency is also permitted.

* There is a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/ interstitial lung disease.

* There are any active infections requiring therapy.

* There is uncontrolled human immunodeficiency virus (HIV) infection. HIV-infected participants with well-controlled HIV may enroll.

* There is a positive test result for hepatitis B virus (HBV) or HCV indicating presence of virus (it is expected that all participants will have been serologically tested for hepatitis B in advance of this study, with HBsAG, anti-HBc IgG, and anti-HBs as per ASCO 2020 Provisional Clinical Opinion \[PCO\] on universal Serologic testing for hepatitis B at the onset of anticancer therapy; screening should also include an anti-HCV test prior to start of cancer treatment:

* There is a history or clinical evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study or interfere with the participant's participation for the full duration of the study

* Known psychiatric or substance abuse disorder that would interfere with cooperation with study requirements.

* There is a known history of regular illicit drug use and/or recent history (within the last year) of substance abuse (including alcohol).

* Participant is pregnant, breastfeeding, or planning to conceive or father children within the projected duration of the study.

* Participant is currently receiving medications known to be strong inhibitors or inducers of CYP3A4 and CYP1A2.