linavonkibart (SRK-181) / Scholar Rock - LARVOL DELTA

SRK-181 Alone or in Combination With Anti-PD-(L)1 Antibody Therapy in Patients With Locally Advanced or Metastatic Solid Tumors (DRAGON) (clinicaltrials.gov) - P1 | N=112 | Completed | Sponsor: Scholar Rock, Inc. | Active, not recruiting ➔ Completed | Trial completion date: Dec 2024 ➔ Apr 2025 | Trial primary completion date: Dec 2024 ➔ Apr 2025

Trial completion • Trial completion date • Trial primary completion date • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Oropharyngeal Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer • ALK • EGFR

DRAGON trial: durable remission rate with the latent TGFβ1 inhibitor linavonkibart (SRK-181) and pembrolizumab in patients with immune checkpoint inhibitor resistant advanced cancers (SITC 2024) - P1 | "Baseline biomarker data from ccRCC patients showed clinical outcomes correlated with CD8+ infiltration and elevated Treg Levels, suggesting a potential patient selection strategy. These data support further investigation of linavonkibart."

Checkpoint inhibition • Clinical • IO biomarker • Metastases • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer • CD8 • TGFB1

Phase 1 Study Results of SRK-181 (Linavonkibart), A Latent TGFβ1 Inhibitor, Combined with Pembrolizumab in Anti-PD1 Resistant ccRCC Patients (KCRS 2024) - No abstract available

Clinical • P1 data • Clear Cell Renal Cell Carcinoma • TGFB1

Phase 1 study (DRAGON) of SRK-181 (linavonkibart), a latent TGFβ1 inhibitor, combined with pembrolizumab in patients with anti-PD1 resistant advanced solid tumors: Updated results of expansion part. (ASCO 2024) - P1 | "Combination treatment with LKT+P is associated with enhanced proinflammatory microenvironment with promising efficacy in anti-PD-1 resistant pts across multiple tumor types with manageable safety profile. The result supports LKT as a potential treatment to overcome immune checkpoint inhibitor-associated resistance."

Clinical • IO biomarker • Metastases • P1 data • Clear Cell Renal Cell Carcinoma • Dermatitis • Dermatology • Fatigue • Head and Neck Cancer • Immunology • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Pruritus • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer • CD8 • TGFB1

Scholar Rock Presents New Data from SRK-181 Phase 1 DRAGON Trial at ASCO 2024 Annual Meeting (Businesswire) - P1 | N=112 | DRAGON (NCT04291079) | Sponsor: Scholar Rock, Inc. |"Scholar Rock...announced encouraging data from its Phase 1 DRAGON proof-of-concept trial of SRK-181...in combination with pembrolizumab in patients with advanced solid tumors....Data were shared in an oral presentation during the...ASCO Annual Meeting....Safety data from all cohorts in the dose expansion phase (Part B; n=78 patients; 1500 mg q3w) continued to show SRK-181 was generally well tolerated when used in combination with pembrolizumab....An analysis in ccRCC patients showed a positive correlation between baseline CD8+ infiltration status and response rate, with an increase in ORR from 23.3 to 40%, and an improvement in median durability of response (mDoR) from 7.7 to 9.3 months if enrollment had been limited to patients whose tumors were infiltrated by CD8+ T-cells at baseline."

Biomarker • P1 data • Clear Cell Renal Cell Carcinoma • Melanoma • Non Small Cell Lung Cancer • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer

Scholar Rock to Present New Data from SRK-181 Phase 1 DRAGON Trial at the American Society of Clinical Oncology (ASCO) Annual Meeting (Businesswire) - P1 | N=112 | DRAGON (NCT04291079) | Sponsor: Scholar Rock, Inc. | "Scholar Rock...announced it will present new data from its Phase 1 DRAGON proof-of-concept trial of SRK-181 in combination with pembrolizumab in patients with advanced solid tumors in an oral presentation during the American Society of Clinical Oncology (ASCO) Annual Meeting being held May 31 – June 4 in Chicago....Biomarker data showed that the SRK-181 + pembrolizumab treatment combination created an enhanced proinflammatory microenvironment in anti-PD-(L)1 resistant patients. Patients with ccRCC whose tumors were infiltrated at baseline by CD8+ T cells and/or regulatory T cells showed positive correlations between infiltration of each cell type and response rate. This positive correlation between baseline infiltration status type and response rate suggests a potential patient selection strategy."

Biomarker • P1 data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Head and Neck Cancer • Kidney Cancer • Melanoma • Oncology • Renal Cell Carcinoma • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer

Scholar Rock Reports First Quarter 2024 Financial Results and Highlights Business Progress (Businesswire) - "New SRK-181 data from the Phase 1 DRAGON proof-of-concept trial selected for an oral presentation at the ASCO Annual Meeting being held May 31- June 4, 2024 in Chicago."

P1 data • Oncology • Solid Tumor

SRK-181 Alone or in Combination With Anti-PD-(L)1 Antibody Therapy in Patients With Locally Advanced or Metastatic Solid Tumors (DRAGON) (clinicaltrials.gov) - P1 | N=112 | Active, not recruiting | Sponsor: Scholar Rock, Inc. | Recruiting ➔ Active, not recruiting | N=74 ➔ 112 | Trial primary completion date: Dec 2023 ➔ Dec 2024

Combination therapy • Enrollment change • Enrollment closed • Metastases • Trial primary completion date • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Oropharyngeal Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer • ALK • EGFR

Establishing proof of mechanism in patients: preliminary biomarker data of SRK-181 (a latent TGFβ1 inhibitor) from DRAGON Study (SITC 2023) - P1 | "Conclusions These biomarker results from the DRAGON study are consistent with preclinical findings and provide proof of mechanism in the clinic that selectively targeting latent TGFb1 with SRK-181 can overcome the immune suppressive environment associated with CPI resistance. Part B enrollment is ongoing."

Biomarker • Clinical • IO biomarker • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Urothelial Cancer • CD8 • TGFB1

Safety, efficacy, and biomarker results of SRK-181, a latent TGFβ1 inhibitor, in anti-PD-1 resistant metastatic ccRCC patients (SITC 2023) - P1 | "Conclusions As of 26 May 2023, combination treatment of SRK-181 and anti-PD-1 (pembrolizumab) was generally well tolerated with an ORR of 25% and clinical benefit rate of 69% in heavily pre-treated, anti-PD-1-refractory ccRCC patients. Enrollment is ongoing for all cohorts."

Biomarker • Clinical • IO biomarker • Metastases • Clear Cell Renal Cell Carcinoma • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Urothelial Cancer • TGFB1

Scholar Rock Presents New Data from Phase 1 DRAGON Trial Showing Promising Anti-Tumor Activity in Anti-PD-1 Resistant Metastatic ccRCC Patients and Supporting SRK-181 Continued Tolerability (Businesswire) - P1 | N=74 | DRAGON (NCT04291079) | Sponsor: Scholar Rock, Inc. | "These data will be presented in two poster presentations during the Society for Immunotherapy of Cancer's (SITC) 38th Annual Meeting...Of 28 evaluable patients in the ccRCC cohort, six patients treated with SRK-181 in combination with pembrolizumab had confirmed partial responses (PRs) and achieved a best tumor reduction of 33% to 93%, with an objective response rate (ORR) of 21.4%. In the biomarker analysis for ccRCC, levels of circulating granulocytic myeloid-derived suppressor cells (gMDSC) correlated with clinical activity in ccRCC patients treated with SRK-181 in combination with pembrolizumab. The data cutoff for all analyses was August 29, 2023."

Biomarker • P1 data • Clear Cell Renal Cell Carcinoma

Scholar Rock to Present Clinical and Biomarker Data from the Phase 1 DRAGON Trial at the SITC 38th Annual Meeting (Businesswire) - "Scholar Rock... announced today that it will present data from DRAGON, a Phase 1 study of SRK-181 in patients with advanced solid tumors at the Society for Immunotherapy of Cancer (SITC) 38th Annual Meeting in San Diego on November 1-5. In one poster presentation, Scholar Rock will share preliminary biomarker data from Part B of the trial, and in a second poster presentation, provide safety, efficacy, and biomarker results of SRK-181 in anti-PD-1 resistant metastatic clear cell renal cell carcinoma (ccRCC) patients from both Parts A and B."

Biomarker • P1 data • Clear Cell Renal Cell Carcinoma

SRK-181 Alone or in Combination With Anti-PD-(L)1 Antibody Therapy in Patients With Locally Advanced or Metastatic Solid Tumors (DRAGON) (clinicaltrials.gov) - P1 | N=74 | Recruiting | Sponsor: Scholar Rock, Inc. | N=200 ➔ 74

Combination therapy • Enrollment change • Metastases • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Oropharyngeal Cancer • Renal Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • ALK • EGFR

Scholar Rock Reports Second Quarter 2023 Financial Results and Highlights Business Progress (Businesswire) - "DRAGON is evaluating SRK-181 in patients with locally advanced or metastatic solid tumors that exhibit resistance to anti-PD-(L)1 antibodies. The Company will provide biomarker and clinical updates from Part B of the DRAGON trial in the second half of 2023."

Biomarker • P1 data • Oncology • Solid Tumor

SRK-181, a latent TGFβ1 inhibitor: safety, efficacy, and biomarker results from the dose escalation portion of a phase I trial (DRAGON trial) in patients with advanced solid tumors (SITC 2022) - P1 | "No DLT was observed up to 3000mg q3w/2000mg q2w as monotherapy and up to 2400mg q3w as combination treatment. Early evidence of efficacy was observed with prolonged stable disease and a confirmed PR."

Biomarker • Clinical • IO biomarker • P1 data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Non-melanoma Skin Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • Urothelial Cancer • TGFB1

Scholar Rock Reports First Quarter 2023 Financial Results and Highlights Business Progress (Businesswire) - "Advancing Phase 1 DRAGON proof-of-concept trial. In the second half of 2023, the company expects to provide biomarker and clinical updates from Part B of the DRAGON trial....Research and development expense was $29.7 million for the quarter ended March 31, 2023, compared to $29.4 million for the quarter ended March 31, 2022. The increase was primarily attributable to costs associated with clinical trials, including...the DRAGON trial for SRK-181."

P1 data • Oncology • Solid Tumor

SRK-181 Alone or With Anti–PD-(L)1 Therapy Elicits Early Efficacy in Select Solid Tumors (OncLive) - P1 | N=100 | DRAGON (NCT04291079) | Sponsor: Scholar Rock, Inc. | "When the fully human IgG4 monoclonal antibody SRK-181 was given as a monotherapy or in combination with anti–PD-1 or PD-L1 agents in patients with locally advanced or metastatic solid tumors, it was found to be generally well tolerated and to demonstrate early indications of efficacy, according to data from the phase 1 DRAGON trial...'No dose-limiting toxicities [DLTs] were observed up to 3000 mg every 3 weeks (q3w) or 2000 mg every 2 weeks (q2w) as a monotherapy and up to 2400 mg every 3 weeks as combination treatment.'"

P1 data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Skin Cancer • Solid Tumor • Urothelial Cancer

Safety, pharmacokinetics, efficacy, and biomarker results of SRK-181 (a latent TGFβ1 inhibitor) from a phase I trial (DRAGON trial) (ESMO-TAT 2023) - P1 | "No DLTs were observed up to 3000mg q3w/2000mg q2w as monotherapy and up to 2400mg q3w as combination treatment. Early signs of efficacy were observed with 3 cPR in pts with anti-PD-1 resistant ccRCC."

Biomarker • Clinical • IO biomarker • P1 data • PK/PD data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Solid Tumor • Urothelial Cancer • TGFB1

[VIRTUAL] DRAGON: Phase 1 trial of SRK-181, a latent TGFβ1 inhibitor in combination with anti-PD-(L)1 inhibitors for patients with solid tumors unresponsive to anti-PD-(L)1 therapy alone (SITC 2020) - P1 | "PD effects will be assessed by measuring modulation of tumor immune cells and TGFb pathway within the tumor microenvironment. Results N/A Conclusions An enrollment update will be provided"

Clinical • Combination therapy • P1 data • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Urothelial Cancer • TGFB1

[VIRTUAL] DRAGON: Phase 1 trial of SRK-181, a latent TGFβ1 inhibitor in combination with anti-PD-(L)1 inhibitors for patients with solid tumors unresponsive to anti-PD-(L)1 therapy alone (SITC 2020) - P1 | "PD effects will be assessed by measuring modulation of tumor immune cells and TGFb pathway within the tumor microenvironment. Results N/A Conclusions An enrollment update will be provided"

Clinical • Combination therapy • P1 data • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Urothelial Cancer • TGFB1

Scholar Rock Reports Full Year 2022 Financial Results and Highlights Business Progress (Businesswire) - "SRK-181 is an investigational selective inhibitor of latent TGFβ-1 activation and is being developed with the aim of overcoming resistance to checkpoint therapy in patients with advanced cancer. Continue to progress Phase 1 DRAGON trial. The company expects to provide biomarker and clinical updates from the DRAGON proof-of-concept trial throughout 2023....Encore data from DRAGON will be presented at the European Society for Medical Oncology Targeted Anticancer Therapies (ESMO TAT) Congress in Paris, France on March 7 at 11:05-12:30 p.m. EST."

P1 data • Oncology • Solid Tumor

SRK-181 Alone or in Combination With Anti-PD-(L)1 Antibody Therapy in Patients With Locally Advanced or Metastatic Solid Tumors (DRAGON) (clinicaltrials.gov) - P1 | N=200 | Recruiting | Sponsor: Scholar Rock, Inc. | Trial completion date: Jul 2022 ➔ Dec 2024 | Trial primary completion date: Dec 2021 ➔ Dec 2023

Combination therapy • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • ALK • EGFR

Recent Phase 1 DRAGON Data Show SRK-181 Continues to be Well Tolerated with Early Indications of Efficacy (Businesswire) - P1 | N=200 | DRAGON (NCT04291079) | Sponsor: Scholar Rock, Inc | "Safety data from the dose escalation portion of the trial (Part A) continue to show SRK-181 is generally well tolerated when used alone or in combination with anti-PD-(L)1 checkpoint inhibitor therapy. No dose-limiting toxicities were observed in patients receiving SRK-181 as monotherapy (Part A1) when dosed up to 3000 mg once every three weeks (q3w) or 2000 mg once every two weeks (q2w), or in patients receiving SRK-181 in combination with checkpoint inhibitor therapy (Part A2) when dosed up to 2400 mg q3w. All dose levels were generally well tolerated, including the recommended SRK-181 dose of 1500 mg q3w or 1000 mg q2w in combination with anti‑PD-(L)1 for the dose expansion portion of the trial (Part B)."

P1 data • Oncology • Solid Tumor

First-in-Human Phase 1 trial of SRK-181: a latent TGFβ1 inhibitor, alone or in combination with anti-PD-(L)1 treatment in patients with advanced solid tumors (DRAGON trial) (SITC 2021) - P1 | "In Part A2, 10 patients were treated with SRK-181 at doses of 240, 800 and 1600mg Q3W+pembrolizumab. Next planned dose in Part A2 will be 2400mg Q3W. Trial Registration DRAGON trial (NCT04291079)"

Clinical • Combination therapy • P1 data • Bladder Cancer • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Liver Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Oropharyngeal Cancer • Ovarian Cancer • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor • Urothelial Cancer • TGFB1

Scholar Rock to Present Data from the Phase 1 DRAGON trial at the SITC 37th Annual Meeting (Businesswire) - "Scholar Rock...announced it will present data from DRAGON, a Phase 1 proof-of-concept study of SRK-181 in patients with advanced solid tumors. Safety, efficacy, and biomarker results from Part A (dose escalation) and an update on Part B (dose expansion) will be presented as a poster at the Society for Immunotherapy of Cancer’s (SITC) 37th Annual Meeting in Boston on November 8-12....'We are encouraged by the early clinical data from the ongoing DRAGON Phase 1 clinical trial and look forward to sharing these results at SITC, as well as at future medical meetings as more SRK-181 data from both Part A and B become available'."

Biomarker • P1 data • Oncology • Solid Tumor