New interim phase II data from Replimune Group Inc., of Woburn, Mass., show RP-1 and Opdivo (nivolumab, Bristol-Meyers Squibb Co.) produced multiple complete responses and a high rate of deep responses in anti-PD-1/anti-CTLA-refractory melanoma.

The company said the new data support its plans to studying the combination for treating melanoma and for cutaneous squamous cell carcinoma (CSCC), which the phase I/II trial is investigating.

The findings also prompted the company to say it will enroll a 30-patient cohort of patients with anti-PD-1-refractory non-small-cell lung cancer (NSCLC) and terminate enrolling its cohort of patients with metastatic bladder cancer.

SVB Leerink analysts wrote Wednesday that RP-1 and Opdivo “have been administered safely into lung tumors and demonstrated an ability to shrink lung metastases. The company said the data support proof of principle in treating NSCLC with RP-1, its candidate based on a strain of herpes simplex virus engineered to maximize tumor killing potency, the immunogenicity of tumor cell death and the activation of a systemic antitumor immune response.

The analysts said they were encouraged by melanoma numbers “although patient numbers remain small with relatively short follow-up” and said they view the company as a “high-quality story led by an experienced management team.”

The news failed to move the company stock (NASDAQ:REPL) much, as it moved slightly upward by 1.15% on June 3 to close at $20.19. A year ago, on June 3, 2019, shares went for $13.90. The 52-week low was $8.58 per share and the peak was $22.13.

The new Replimune data come from a phase I/II study of RP-1 in CSCC and anti-PD-1-refractory melanoma. The company said it has a strong efficacy signal from the study that causes it to be optimistic that its currently enrolling 125-patient cohort could support regulatory approval.

The phase II study produced data in cutaneous squamous cell carcinoma that were presented late in 2019. Four of seven evaluable patients have ongoing complete responses and six of those seven have an ongoing complete or partial response, compared to one out of five patients and two out of five on Opdivo-only, respectively. The data continue to demonstrate that RP-1 in combination with Opdivo is well-tolerated, demonstrates immune activation and continues to drive deep and durable responses in patients with CSCC.

Replimune said it made the decision to drop out of bladder cancer, “in light of changes to the competitive landscape.” The field is indeed crowded. Cortellis lists 63 drugs in active development for metastatic bladder cancer. And in March, Astrazeneca plc stumbled in its efforts with previously untreated cases of advanced bladder cancer as neither its immune checkpoint inhibitor, Imfinzi (durvalumab), nor a pairing of it with the investigational drug tremelimumab beat standard-of-care chemotherapy in improving overall survival during a phase III trial evaluating the treatments as first-line care for patients with advanced disease.

Just two checkpoint agents, Merck & Co. Inc.'s Keytruda (pembrolizumab) and Roche Holding AG’s Tecentriq (atezolizumab), are approved for first-line bladder cancer care, but only for certain patients ineligible for cisplatin-containing chemo. However, they've been challenged by trials showing lower survival in some patients with low levels of PD-L1, leading the EMA to recommend restricting their use only to patients with high levels of the cancer protein.

Merck is taking a different tack as it is joining Daiichi Sankyo Co. Ltd., of Tokyo, to evaluate the combination of DS-1062, a TROP2-directed DXd antibody-drug conjugate (ADC), and Keytruda (pembrolizumab) in patients with previously treated advanced or metastatic NSCLC without actionable genomic alterations. There are no TROP2-directed therapies and no ADCs approved for treating NSCLC, which often overexpresses the TROP2 protein, the companies said.

The 2018 market leaders in NSCLC, according to DRG, are Merck’s Keytruda with $4.74 billion in sales, Alimta (pemetrexed) from Eli Lilly and Co. with $1.7 billion in sales and Opdivo. DRG anticipates $39.38 billion in U.S., European and Japanese sales by 2028.

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