50% overall response rate (ORR) and 75% clinical benefit rate, including one complete response in urothelial cancer at the 5 mg/m2 dose on an intent-to-treat (ITT) basis
As of
Confirmed RECIST responses in non-small cell lung cancer (NSCLC) and breast cancer patients
Conference call scheduled for
“We are encouraged by the Phase I dose escalation results as they continue to demonstrate the potential for BT8009 to be best-in-class for the treatment of urothelial cancer based on the observed anti-tumor activity and tolerability profile as well as the potential to treat other tumor types with significant unmet need,” said
“These data reaffirm the possibility for BT8009 to become a significant new treatment option for patients,” said
“BT8009 has the potential to become an important player in the treatment landscape for urothelial cancer and other solid tumors,” said
BT8009, a BTC targeting Nectin-4, has demonstrated anti-tumor activity in heavily pre-treated urothelial, lung and breast cancer patients with signs of differentiation compared to antibody-based approaches. Bicycle established two recommended Phase II doses (RP2Ds) at 5 mg/m2 weekly and 7.5 mg/m2 2 weeks on, 1-week off (over a 21-day cycle). The company is currently focusing its efforts on the 5 mg/m2 weekly dose and enrollment in the expansion cohorts remains ongoing.
- Preliminary signs of anti-tumor activity observed. As of the
September 20, 2022 data cut off, 49 patients were dosed in the Phase I escalation portion of the ongoing Phase I/II trial with a median of three prior lines of therapy.- A total of 24 urothelial cancer patients were dosed. Of these, eight patients were dosed at the RP2D of 5 mg/m2 weekly.
- Among these eight patients, one patient had a complete response (13%), and three patients had a partial response (38%) under the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, resulting in an ITT ORR of 50%. Two additional patients had stable disease for over 16 weeks, resulting in a clinical benefit rate (CBR) of 75%. The remaining two patients in the cohort consisted of one stable disease and one non-evaluable patient.
- Of the eight urothelial patients dosed at 5 mg/m2 weekly, seven were response evaluable. Amongst these seven patients, all (100%) were observed to have at least some degree of tumor shrinkage, including the four with a RECIST version 1.1 response (57% ORR on a response-evaluable basis).
- As of
January 2023 , mDOR is estimated to be approximately 14 months. Two out of four responders in this cohort remain on therapy with ongoing responses.
- Response rates in urothelial patients in the 7.5 mg/m2 2 weeks on, 1-week off (over a 21-day cycle) and 10 mg/m2 every other week cohort were consistent with that of the 5 mg/m2 weekly cohort on an ITT basis. One of two patients in the 7.5 mg/m2 2 weeks on, 1-week off (over a 21-day cycle) cohort had a partial response and two of four patients in the 10 mg/m2 every other week cohort had a partial response, for an ORR of 50% in each of these cohorts. Both of these cohorts deliver the same amount of MMAE payload as the 5 mg/m2 weekly dose over a six-week period.
- Confirmed RECIST response in an NSCLC patient. A confirmed partial response was observed in a 76-year-old patient with Nectin-4 positive metastatic adenocarcinoma. The patient entered the 7.5 mg/m2 2 weeks on, 1-week off (over a 21-day cycle) cohort after four prior lines of therapy, including a checkpoint inhibitor. As of the
September 20, 2022 data cutoff, the patient remains on therapy with an ongoing response. - Confirmed RECIST response in a breast cancer patient. A confirmed partial response was observed in a 79-year-old patient with Nectin-4 positive metastatic adenocarcinoma. The patient entered the 10 mg/m2 every other week cohort after one prior line of therapy. As of
December 2022 , the patient remains on therapy with an ongoing response.
- A total of 24 urothelial cancer patients were dosed. Of these, eight patients were dosed at the RP2D of 5 mg/m2 weekly.
- BT8009 was well tolerated across all 49 patients in the study, with a low incidence of adverse events common to antibody-based approaches. The most common treatment-related adverse events across the study were gastroenterologically related and fatigue. Across all patients at all doses, there was a low incidence of skin rash of any form, eye disorders, neuropathy of any form and no cases of pneumonitis in any patient at any dose. The most common Grade 3 or higher treatment-related adverse event was neutropenia: seven cases or 14%; four of these were at doses above the RP2Ds. There were three subjects with serious adverse events (SAEs) at or above Grade 3 that were drug related (6%). Of these, none was in the 5 mg/m2 cohort. Median percentage relative dose intensity was 99%, reflecting a low level of dose modifications especially for a Phase I dose escalation trial in a heavily pre-treated population.
- BT8009 well tolerated at or below the two RP2Ds. At or below the RP2Ds of 5 mg/m2 weekly and 7.5 mg/m2 2 weeks on, 1-week off (over a 21-day cycle), treatment-related dose modifications were rare. There were no treatment-related discontinuations. The incidence of Grade 3 or higher related adverse events at or below the two RP2Ds was low. At the 5 mg/m2 weekly dose, there were no cases of Grade 3 or higher skin rash, eye disorders, neuropathy or pneumonitis.
Bicycle advancing BT8009 in ongoing expansion cohorts. In
Poster Presentation Details
Title: BT8009-100: A Phase I/II Study of a Novel Bicyclic Peptide and MMAE Conjugate BT8009 in Patients with Advanced Malignancies Associated with Nectin-4 Expression, Including Urothelial Cancer
Abstract #: 498
Presenter:
Session Title: Poster Session B: Prostate Cancer and Urothelial Carcinoma
Date/Time:
Conference Call Details
About
Forward-Looking Statements
This press release may contain forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may be identified by words such as “aims,” “anticipates,” “believes,” “could,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “seeks,” “will” and variations of these words or similar expressions that are intended to identify forward-looking statements, although not all forward-looking statements contain these words. Forward-looking statements in this press release include, but are not limited to, statements regarding: the potential of BT8009 to target and kill cancer tumor cells; the initiation, progress, and timing of clinical trials of BT8009 and pursuit of additional indications for and further clinical development of this product candidate. Bicycle may not actually achieve the intentions or expectations disclosed in these forward-looking statements, and you should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the intentions and expectations disclosed in these forward-looking statements as a result of various factors, including: whether the outcomes of preclinical studies will be predictive of clinical trial results; the risk that trials and studies may be delayed and may not have satisfactory outcomes; and other important factors, any of which could cause Bicycle’s actual results to differ from those contained in the forward-looking statements, are described in greater detail in the section entitled “Risk Factors” in Bicycle’s Quarterly Report on Form 10-Q filed with the
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